| Candy et al. Treatment of faecal impaction with polyethelene glycol plus electrolytes (PGE + E) followed by a double-blind comparison of PEG + E versus lactulose as maintenance therapy. 2006. Journal of Pediatric Gastroenterology and Nutrition 43[1], 65-70 | Study Type:
Double-blind
RCT**
Evidence level:
1+
Study aim:
to assess the efficacy of polyethylene glycol 3350 plus electrolytes (PEG + E; Movicol ®) as oral monotherapy in the treatment of faecal impaction in children and to compare PEG + E with lactulose as maintenance therapy in a randomised trial | 65 children
Inclusion criteria:
children aged 2 to 11 years with intractable constipation that had failed to respond to conventional treatment and would require hospital admission for disimpaction (otherwise been admitted for enemas, manual removal or intestinal lavage with PEG + E solutions)
Exclusion criteria:
any condition contraindicate ng the use of PEG+E or lactulose, including intestinal perforation or obstruction, allergy to any of the ingredients of the trial products, paralytic ileus, toxic megacolon, Hirschsprung's disease, severe inflammatory bowel disease, uncontrolled renal/hepatic/cardiac disease, uncontrolled endocrine disorder or any neuromuscular condition affecting the bowel |
- -
Phase 1: 65 children - -
Phase 2: 58 children
67% boys
Mean age: 5.7 ± 2.6 years
(range 2 to 11 years)
Country:
UK | Intervention:
Polyethylene glycol 3350 (13.8 g powder dissolved in at least 125 ml water per sachet) plus electrolytes (PEG + E; Movicol ®)
Comparison:
Lactulose (10 g powder dissolved in at least 125 mL water)
For both medications children received oral maintenance doses commencing with ½ of the numbers of sachets required for disimpaction/day
Disimpaction regime (n sachets):
2 to 4 years Day 1: 1 Day 2: 2 Day 3: 2 Day 4: 3 Day 5: 3 Day 6: 4 Day 7: 4
5 to 11 years Day 1: 2 Day 2: 3 Day 3: 4 Day 4: 5 Day 5: 6 Day 6: 6 Day 7: 6
Additional laxative treatment with senna allowed as rescue medication if the response to a single agent alone was judged inadequate by investigator | Duration of treatment
12 weeks
Assessment point (s):
Immediately after treatment finished
Follow-up period:
No follow-up made after treatment finished
Outcome Measures:
Primary efficacy endpoint: - -
number of successful defecations/week
Secondary efficacy endpoints: - -
reimpaction rate - -
number of sachets used each day - -
use of senna as rescue medication - -
amount of stool - -
predominant bowel movement form - -
pain - -
straining - -
rectal bleeding - -
abdominal pain - -
soiling - -
overall assessment of treatment
Safety
| Number of successful defecations/week (last on-treatment value)
Mean, SD, range
- -
PEG+E (n=27):
Lactulose (n=26): Difference in means: 3.5
95% CI: 1.0 to 6.0
p=0.007
Reimpaction rate (n, % children):
- -
PEG+E (n=27): 0 - -
Lactulose (n=26): 7 (23%)
p=0.011
Number of sachets used each day:
- -
PEG+E (n=27): 0.91 (0.41) - -
Lactulose (n=26): 2.41 (0.91)
Use of senna as rescue medication
- -
PEG+E (n=27): 0 - -
Lactulose (n=26): 8 (31%)
p=0.002
No significant differences in mean values per patient between 2 groups with respect to: amount of stool, predominant bowel movement form, pain, straining, rectal bleeding, abdominal pain, soiling and overall assessment of treatment
Safety (% children) (n=58):
- -
PEG+E: 64 - -
Lactulose: 83
Similar incidence in each age group. Most commonly reported events gastrointestinal and resolved during the study. No clinically significant abnormal values observed in urine and plasma electrolytes after 12 weeks of maintenance therapy | Additional information from study:
Sample size: intended to recruit 60 children to obtain approximately 45 children continuing to end of phase 2
Children and investigators blinded to medication which was dispensed according to randomisation list generated by the study sponsor
Blindness reasonably maintained as appearance of 2 products very similar and both packed in sachets of an identical size
5 children did not complete phase 1: 3 children withdrew before receiving any study medication and 2 children failed to disimpact within the time allowed
58 children entered phase 2. 5 were excluded from the ITT population as they did not provide any on-treatment efficacy data.
10 children (17%) did not complete phase 2: 7 on lactulose reimpacted, 2 on lactulose did not want to continue, 1 on PEG+E did not complete the diary card
No significant differences at baseline between 2 groups regarding: age, sex, height and weight
No children withdrew form the study for safety reasons
Reviewer comments:
No clear definition of constipation given
Method of allocation concealment not described
Results not controlled for confounders
Missing data on 2 children who did not enter phase 2 of the study
Source of funding: supported by Norgine Pharmaceuticals Ltd. |
| Voskuijl et al. PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial. 2004. Gut 53[11], 1590-1594 | Study Type:
RCT
Evidence level:
1+
Study aim:
to compare the clinical efficacy and safety of PEG 3350
(Transipeg; polyethylene glycol with electrolytes) and lactulose in paediatric constipation | 100 children
Inclusion criteria:
children aged 6 months to 15 years with constipation
Exclusion criteria:
Organic causes for defecation disorders, including Hirschsprung's' disease, spina bifida occulta or hypothyroidism | 91 children
49 male
age range: 6
months to 15 years
Age (y) (mean (SD))
PEG 3350 6.5 (3.2)
Lactulose 6.5 (3.4)
Country:
the Netherlands | Run-in phase (1 week before treatment):
No laxatives allowed. At the end all patients received 1 enema daily for 3 days:
- -
Children ≤ 6 years: 60 ml Klyx (sodium dioctylsulfosuccin ate and sorbitol) - -
Children > 6 years: 120 ml Klyx
1. Initial phase:
Intervention:
PEG 3350
- -
children aged 6 months to 6 years (inclusive): one sachet (2.95g) per day - -
children older than 6 years: 2 sachets (5.9g) per day
Comparison:
Lactulose
- -
children aged 6 months to 6 years (inclusive): one sachet (6g) per day - -
children older than 6 years: 2 sachets (12g) per day
2. Follow-up phase Intervention:
PEG 3350
- -
children aged 6 months to 6 years (inclusive): one sachet (2.95g) per day - -
children older than 6 years: 2 sachets (5.9g) per day
Comparison:
none | Duration:
8 weeks (RCT)
18 weeks (case series)
Assessment point (s):
1, 2, 4 and 8 weeks after starting treatment
Follow-up period:
26 weeks after entering case series phase
Outcome Measures:
Efficacy: - -
frequency of stools - -
frequency of encopresis - -
overall treatment success
Safety - -
Incidence and severity of gastrointestinal adverse effects
| Defecation frequency/week
- -
PEG 3350: 7.12 (5.14) - -
Lactulose: 6.43 (5.18)
N.S
Encopresis frequency/week:
- -
PEG 3350: 3.11 (5.41) - -
Lactulose: 2.84 (3.59)
N.S
Success percentages (95% CI)
PEG 3350: 56 (39 to 70)
Lactulose: 29 (16 to 44)
P=0.02
Overall treatment success independent of age (< 6 years and ≥ 6 years) and use of laxatives for more than 1 year prior to the start of the study. In children treated for less than 1 year a significant difference in success found between those treated with PEG 3350 (63%) or lactulose (31%), p=0.02
Medication (sachet/day):
- -
PEG 3350: 1.99 (0.3) - -
Lactulose: 2.4 (0.4)
p=0.03
no significant differences between 2 groups at 1, 2, 4 and 8 weeks for defecation and encopresis frequency
Side effects:
No serious or significant side effects recorded Significantly more adverse effects (abdominal pain, pain at defecation and straining at defecation) in patients taking lactulose as compared to PEG (p<0.05). No significant differences between 2 groups regarding: bloating, diarrhoea, flatulence, nausea, hard stool consistency and vomiting. Significantly more children complained of bad palatability of PEG compared to lactulose and this caused the premature withdrawal of 1 patient. | Additional information from study:
Childhood constipation defined as having at least 2 to 4 of the following symptoms for the last 3 months: less than 3 bowel movements/week, encopresis more than once/week, large amounts of stool every 7 to 30 days (large enough to clog the toilet) and palpable abdominal or rectal mass on physical examination
Estimated that a total sample of 90 patients would be adequate to show a difference of at least 30% more success at 8 weeks using PEG 3350 compared to lactulose, with a 2 tailed alpha level of 0.05 with a power of 80%
Unlabelled number boxes with unlabelled sachets prepared by the AMC pharmacy and handed out to patients after randomisation. The box contained 180 sachets containing either lactulose 6g/sachet or PEG 3350 2.95g per sachet.
Toilet training advised after each meal (5 minutes) and small gifts and praise used to enhance compliance
No significant differences at baseline between the 2 groups with respect to: age, sex, defecation frequency, encopresis, large amounts of stool and faecal impaction
9 dropouts: 4 on PEG 3350, 5 on lactulose. 2/each group lost to follow-up, 1/each group reason unknown. 2 on lactulose were helicobacter positive, 1 on PEG due to bad palatability of study medication
Overall treatment success defined 3 or more bowel movement/week and 1 encopresis episode or less every 2 weeks
Reviewer comments:
Method of randomisation and allocation concealment not described
Case series phase outcomes not reported for the purpose of this review ITT analysis not performed
Source of funding: not stated |
| Loening-Baucke et al. A randomized, prospective, comparison study of polyethylene glycol 3350 without electrolytes and milk of magnesia for children with constipation and fecal incontinence. 2006. Pediatrics 118[2], 528-535 | Study Type:
RCT
Evidence level:
1-
Study aim:
to compare the efficacy, safety and patient acceptance of polyethylene glycol (PEG) 3350 without added electrolytes vs. milk of magnesia (MOM) over 12 months | 79 children
Inclusion criteria:
age ≥ 4 years and presence of functional constipation with faecal incontinence
Exclusion criteria:
stool toileting refusal, faecal incontinence but no constipation, previous refusal of one of study medications, children who came from far away for a second opinion, Hirschsprung's disease, chronic intestinal pseudo-obstruction, previous surgery involving colon or anus | 79 children
65 boys
age range: 4 to 16.2 years
(median 7.4; mean 8.1 ± 3.0)
Country:
USA | General:
disimpacted with 1 or 2 phosphate enemas in the clinic on the day of the visit , if necessary and started laxative therapy that evening
Intervention:
polyethylene glycol (PEG) 3350 without added electrolytes 0.7 g/kg body weight daily for 12 months
capful of PEG (17 g) mixed in 8 oz of beverage (juice, Kool-Aid, Crystal Light or water) making a solution of ~2g/30 mL
Comparison:
milk of magnesia (MOM) 2mL/kg body weight daily for 12 months
plain MOM could be mixed into apple sauce or milkshakes, or chocolate and other flavouring could be added
Large doses of both medications could be divided into 2 doses | Duration of treatment:
12 months
Assessment point (s):
1, 3, 6 and 12 months after initiating treatment
Follow-up period:
No follow-up made after treatment finished
Outcome Measures:
Primary outcomes: - -
improvement - -
recovery
Secondary outcomes: - -
improvement in stool frequency per week - -
improvement in episodes of faecal incontinence per week - -
resolution of abdominal pain - -
safety profile - -
patient's acceptance and compliance
| Improvement rate (%)
- -
at 12 months: PEG (n=34): 62 MOM (n=21): 43
NS
Recovery rate (%)
- -
at 12 months: PEG (n=34): 33 MOM (n=21): 23
NS
Bowel movement frequency (mean ± SD, episodes/week)
- -
Baseline: PEG (n=39): 3.5 ± 3.7 MOM (n=40): 3.5 ± 6
- -
at 12 months: PEG (n=34): 6.8 ± 3.1 MOM (n=21): 8.2 ± 3.9
P<0.005 for both groups compared to baseline
Faecal Incontinence frequency (mean ± SD, episodes/week)
- -
Baseline: PEG (n=39): 12.2 ± 13 MOM (n=40): 13.5 ± 15.5
- -
at 12 months: PEG (n=34): 1.4 ± 3.5 MOM (n=21): 0.5 ± 1.6
P<0.005 for both groups compared to baseline
Abdominal pain (%)
- -
Baseline: PEG (n=39): 71.8 MOM (n=40): 52.5
- -
at 12 months: PEG (n=34): 3 MOM (n=21): 0
P<0.005 for both groups compared to baseline
At 12-month frequency of bowel movements, frequency of episodes of faecal incontinence, and percentage of children with abdominal pain not significantly different between PEG and MOM group
Patient Acceptance
Several children complained about taste of PEG and MOM.
2 children (5%) continued to refuse PEG vs. 14 children (35%) continued to refuse MOM during the 12 months of the study (P < .001
Treatment doses (mean ± SD):
- -
PEG (g/kg body weight)
1 month: 0.7 ± 0.2 3 months: 0.6 ± 0.3 additional senna at some point: 3 children - -
MOM (mL/kg body weight)
mean doses similar in children who improved and who did not improve for both treatments
safety profiles
PEG: 1 child allergic No other significant clinical effects for either medication, apart from transient diarrhoea disappearing with dose reduction
- -
Laboratory tests: PEG: 1 child with elevated platelets before and after treatment, 1 child with decreased sodium levels at 6 months, but normal at 12 months MOM: 1 child high platelet count, 1 low serum sodium level, elevated AST, 1 elevated ALT
| Additional information from study:
Functional constipation defined by duration of ≥ 8 weeks and ≥ 2 of the following: frequency of bowel movements <3 stools/week, >1 episode of faecal incontinence/week, large stools noted in rectum or felt during abdominal examination, passing of stools so large that they obstructed the toilet
Randomisation performed by children drawing a sealed envelope with and enclosed assignment
Investigators, children and their parents aware of the study group assignment
Estimated that 38 subjects required in each group to be able to detect a difference in failure rates between the 2 groups of 30% in 12 months (40% vs. 10%), at the .05 significance level with .80 power. Authors hypothesized that PEG would be as successful as MOM in treating chronic constipation and faecal incontinence. Authors. previous study showed that 33% of children refused to take MOM during the first 12 months of treatment.
Children treated with minimal effective dosage of PEG or MOM, allowing for a daily stool and preventing abdominal pain and faecal incontinence. Parents instructed to aim for 1 or 2 stools of milkshake consistency each day. Parents asked to increase dosage if stools too hard or not frequent enough and to decrease the dosage if stools watery or too numerous. Small changes, such as 2 oz of PEG or 0.5 tbsp of MOM every 3 days, were recommended. Regular stool sittings for 5 minutes after each meal required initially. Toilet sitting frequency reduced after children recognized urge to defecate and initiated toilet use themselves.
No significant differences at baseline between the 2 groups regarding: age, sex, primary faecal incontinence, previous treatment with laxatives, history of retentive posturing, frequency of bowel movements, bowel movements obstructing the toilet, frequency of faecal incontinence, presence of abdominal pain, presence of abdominal faecal mass and presence of rectal faecal mass
By 12 months a total of 27 dropouts/lost to follow-up. PEG: 2 children lost to follow-up monitoring, 2 (5%) had refused PEG, 1 child allergic to PEG, 2 children were receiving senna. These 7 children counted as not improved and not recovered. MOM: 2
Children lost to follow-up monitoring, 3 children had discontinued study participation, 14 children (35%) had refused to take MOM, and 1 child was receiving senna
Efficacy analyses performed with intention to treat population, other outcomes calculated from available follow-up data
Reviewer comments:
Results not controlled for potential confounders
High drop-out / lost to follow-up rate: 30.4%
Source of funding: Braintree Laboratories (Braintree, MA) supported study with an unrestricted research grant. According to authors, the funding source had no involvement in the study design, collection, analysis, interpretation of data, writing of the report or decision to submit the article for publication |
| Dupont et al. Double-blind randomized evaluation of clinical and biological tolerance of polyethylene glycol 4000 versus lactulose in constipated children. 2005. Journal of Pediatric Gastroenterology and Nutrition 41[5], 625-633 | Study Type:
RCT
Evidence level:
1+
Study aim:
to assess the safety of a polyethylene glycol (PEG) 4000 laxative without additional salts in paediatric patients | 96 children
Inclusion criteria:
children with constipation despite their usual dietary treatment for at least 1 month, aged 6 months to 3 years, ambulatory
Exclusion criteria:
history of intractable faecaloma, Hirschsprung's disease, neurologic, endocrine or metabolic disorders, allergic disease or allergies | 96 children
51 male
- -
Age (months) median (25th to 75th percentiles)
PEG 4000:
28 (19.5–33.7)
Lactulose:
25.8 (12.3–33)
Country:
France | Intervention:
PEG 4000
- -
Starting dose: 1 sachet (4g) and 1 placebo to be taken at breakfast
Comparison:
Lactulose
- -
Starting dose: 1 sachet (3.33g) and 1 placebo to be taken at breakfast
For both drugs, dose could be doubled if ineffective in children aged 13 months to 3 years If maximum authorised dose unsuccessful, one micro-enema of glycerol per day could be prescribed for a maximum of 3 consecutive days. If child not produced stools after treatment 2 enemas could be administered at a 48-h interval. This procedure only allowed twice during the study, If child produced liquid stools for >1 day or > 2 or 3 stools/day depending on age, dose could be decreased by 1 pair of sachets/day to a minimum of 1 pair of sachets every other day and possibly to transitory interruption | Duration of treatment:
3 months
Assessment point (s):
Day 42 (D42) and day 84 (D84) after starting treatment
Follow-up period:
No follow-up performed after treatment finished
Outcome Measures:
- -
Efficacy: stool frequency frequency of hard stools enema use faecal impaction abdominal pain appetite
- -
Biological tolerance: ion electrolytes total protein albumin vitamin A vitamin D folates
- -
Clinical tolerance: body height body weight adverse effects
| Stool frequency (number of stools/wk, median (interquartile range)
- -
D42 NS in babies Toddlers: - -
D84 NS in babies or toddlers
Frequency of hard stools
- -
D42 - -
D84
Enema use
- -
D42: - -
D84:
Faecal impaction
PEG 4000 (n=51): 1 (2%) Lactulose (45): 6 (13%) P=0.049
Abdominal pain disappearance:
- -
D42 - -
D84
Appetite score improvement
PEG 4000 (n=51): +19% Lactulose (45): -4% p<0.003
Clinical tolerance (ITT population)
- -
6 adverse effects (all non serious): - -
median (interquartile range) duration of either new onset or worsened flatulence (days): PEG 4000: 3 (1 to 4.5) Lactulose: 5 (3 to 19.5) P=0.005
- -
median (interquartile range) duration of either new onset or worsened vomiting episodes (days): - -
anal irritation: 5% (2 out of 40 children, both on lactulose) - -
no difference between PEG 4000 and lactulose groups with regards to other digestive tolerance outcomes - -
Body height and body weight unaffected during the 3-monht treatment for both boys and girls
Biological tolerance (ITT population):
No significant difference between treatment groups for the % of children with ONR values on D84 compared to baseline status. No treatment-related changes found in serum iron, electrolytes, total protein, albumin and vitamins A, D and folates
Dose used (sachets/day) (median (interquartile range))
- -
Babies: 1 (0.9 to 1) PEG 1 (1 to 1.3) lactulose P = 0.67
- -
Toddlers
Treatment stopped in 1 child because of lack of efficacy (lactulose group). | Additional information from study:
Constipation defined as less than 1 stool/day for > 1 month in children 6 to 12 months old and less than 3 stools/week for > 3 months in children aged 13 months to 3 years
PEG 4000 and lactulose packaged in a double-blind and double-dummy design, by means of coupled sachets, according to a randomisation list. Double dummy design required because of the difference of taste between the drugs. Numbered boxes provided to investigators at each site in equal numbers. Investigators randomly allocated either PEG 4000 or lactulose to the children for a 3-month period, with the same strategy for dose adaptation
3 children not included because of a baseline laboratory value ONR (out of normal range) before amendment applied. 2 children in PEG 4000 group dropped out before any study drug intake, so the intention to treat population included 51 children (10 babies and 41 toddlers) in the PEG 4000 group and 45 (12 babies and 33 toddlers) in the lactulose group. 76 of these children included in the per protocol analysis and 20 excluded by the independent scientific committee for at least one major deviation, 11 in the PEG 4000 group and 9 in the lactulose group. Reasons for exclusion were no laboratory test at D84, one or more one missing laboratory results at D84, delayed laboratory test at D84 (n = 12), inadequately long exposure to the study drug (n = 2), personal reasons (n = 5) and unauthorized concomitant treatment (n = 1)
No clinically relevant differences between 2 treatment groups at baseline for clinical or biologic parameters Stool frequency, abdominal pain, vomiting, and nausea recorded on Self-Diary Evaluation Booklet
Reviewer comments:
Methods of randomisation and allocation concealment not clearly described No sample calculation performed Results not controlled for potential confounders
Source of funding: not stated |
| Perkin. Constipation in childhood: a controlled comparison between lactulose and standardized senna. 1977. Current Medical Research and Opinion 4[8], 540-543 | Study Type:
RCT
(crossover)
Evidence level:
1-
Study aim:
to compare effectiveness and side effects between a standardised senna syrup and lactulose in the treatment of childhood constipation | 21 children
Inclusion criteria:
children aged
<15 years with a history of constipation treated at home for 3 months or more
Exclusion criteria:
any cause of constipation requiring surgical or medical correction in addition to laxation | 21 children
Country:
UK | Intervention:
Senna syrup 10 to 20 ml daily for 1 week
Comparison:
Lactulose 10 to 15 ml daily for 1 weeks
Each preparation given throughout the appropriate treatment week in a daily dose varied according to the age of the patient
1 intermediate week with not treatment | Duration:
1 week each period with 1 week no treatment in between
Assessment point (s):
immediately after treatment completed
Follow-up period:
No follow up made after treatment finished
Outcome Measures:
- -
stool consistency - -
number of stools passed each day - -
adverse effects
| Number of patients passing stools of any kind each day:
Lactulose vs. Senna
N.S
Number of patients passing normal stools each day (mean)
- -
Lactulose: 13.4 - -
Senna: 8.43 p <0.01
Adverse effects (n patients):
a- senna week:
12 (8 colic, 1 diarrhoea, 2 colic+ diarrhoea, 1 colic + distension)
b- no treatment week: 4 (3 colic, 1 colic + distension)
c- lactulose week
1 (colic)
p<0.001 (a vs. c)
NS (b vs. c) | Additional information from study:
Patients given either treatment according to a code-list of random numbers, placed in a series of sealed envelopes, one of which was opened each time a child entered the trial
1 dropout: 1 patient on senna at the beginning of study failed to attend at the end of 1st week
No written or oral indication of any medical preference for other preparation given and patients presented with single bottle of one or other of the preparations according to the coded instruction at start of trial. On 3rd week a bottle of alternative preparation was given
Outcomes recorded by parents in written diaries
4-point scale of stool consistency: loose, normal, hard, none
Reviewer comments:
No clear definition of constipation given Very small sample size, no sample size calculation Inadequate method of allocation concealment Patients' baseline characteristics not reported
Study not reported as blinded
Results not controlled for confounders
Very short treatment period
According to authors the number of stools passed each day was recorded, but is not reported
Source of funding: not stated |
| Farahmand. A randomised trial of liquid paraffin versus lactulose in the treatment of chronic functional constipation in children. 2007. Acta Medica Iranica 45[3], 183-188Iran, Islamic Republic of. | Study Type:
RCT
Evidence level:
1-
Study aim:
to compare the clinical, efficacy and safety of liquid paraffin and lactulose in the treatment of functional childhood constipation | 247 children
Inclusion criteria:
chronic functional constipation
Exclusion criteria:
organic causes for defecation disorders including Hirschsprung's' disease, spina bifida occulta, hypothyroidism, cystic fibrosis, neurological abnormalities, intestinal pseudo-obstruction | 247 children
127 male
aged 2 to 12 years old (mean 4.1± 2.1 years)
Country:
Iran | General:
1 or 2 enemas daily for 2 days to clear any rectal impaction (30 cc/10 kg of paraffin oil)
Intervention:
Liquid paraffin orally, 1 to 2 ml/kg, twice daily for 8 weeks
Comparison:
Lactulose orally, 1 to 2 ml/kg, twice daily for 8 weeks
For determination of best dose for child, parents asked to increase the volume of each drug by 25% every 3 days as required to yield 1 or 2, firm-loose stools | Duration of treatment:
8 weeks
Assessment point (s):
4 and 8 weeks after treatment started
Follow-up period:
12 weeks after treatment finished
Outcome Measures:
- -
stool frequency - -
encopresis frequency - -
success rate - -
optimal dose of drug - -
side effects
| Stool frequency (mean
± SD)
- -
before treatment (per week): - -
during first 4 weeks (per week): - -
during last 4 weeks (per week):
Encopresis frequency (mean
± SD)
- -
Before treatment (per week): - -
during first 4 weeks (per week): - -
during last 4 weeks (per week):
Success rate (%, CI 95%)
- -
during first 4 weeks: - -
at end of 8 weeks:
Optimal dose of drug
- -
Final effective dose (mean, ml/kg/day):
Side effects (during 4 to 12 week) (not clear whether, n or %, but probably %) (estimates taken from bar chart, outcomes not reported in text):
Lactulose (n=120) Abdominal pain: 10 Bad palatability: 15 Pain at defecation: 10 Bloating: 10 Diarrhoea: 10 Anal oil leakage: 20 Flatulence: 10 Nausea: 10 Hard stool: 20 Vomiting: 0
Liquid paraffin (n=127)
| Additional information from study:
Diagnosis of chronic functional constipation based on having at least 2 of the following symptoms for the last 3 months: less than 3 bowel movements/week, faecal soiling more than once/week, large amounts of stool every 7 to 30 days and palpable abdominal or faecal mass on physical examination
Apart from laxative treatment, parents given instructions to increase their daily fibre intake to an amount of grams equal to their age plus 10. Toilet training after each meal advised to enhance compliance
Treatment success defined as 3 or more bowel movements/week and encopresis episodes less than 2/week
No significant baseline differences between the 2 treatment groups regarding: age, sex, duration of constipation, defection frequency, number of patients with history of encopresis, large amount of stool, faecal impaction in rectum, rectal bleeding, lost to follow-up after 8 weeks, bad palatability of study medication
Reviewer comments:
Method of randomisation and allocation concealment not described
Non blinded study
No sample calculation performed
No withdrawals/dropouts reported
Results not controlled for potential confounders
Source of funding: not stated, but authors reported “no conflicts of interests” |
| Gremse et al. Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children. 2002. Clinical Pediatrics 41[4], 225-229 | Study Type:
RCT (crossover)
Evidence level:
1-
Study aim:
to compare the efficacy of PEG 3350 and lactulose in the treatment of chronic constipation in children | 44 children
Inclusion criteria:
patients aged 2 to 16 years, referred for subspecialty evaluation of constipation
Exclusion criteria:
organic disease of the large or small intestine, known allergy to PEG or lactulose, previous gastrointestinal surgery, renal; or heart failure, bowel obstruction, ileus, pregnancy, lactation, galactosemia, diabetes mellitus | 44 children
Age range: 2 to 16 years (mean 7.8 ± 3.7)
Country:
USA | Intervention:
PEG 3350 without electrolytes (MiraLax) 10g/m2/d orally for 2 weeks
Mean weight adjusted dose: 0.3 g/kg/d (range 0.2 to 0.5)
Comparison:
Lactulose 1.3 g/kg/d orally for 2 weeks
(no washout period) | Duration of treatment:
2 weeks each period
Assessment point (s):
Immediately after each treatment period
Follow-up period:
No follow-up made after treatment completed
Outcome Measures:
- -
Stool frequency - -
Stool form - -
Easy of passage - -
Effectiveness (global assessment, as reported by parent or guardian) - -
Laxative preference (based on efficacy, ease of administration and side effects)
| Mean number of bowel movements
- -
PEG 3350 (n=37): 14.8 ± 1.4 - -
Lactulose (n=37): 13.5 ± 1.5
Stool form (mean sum of scores)
- -
PEG 3350 (n=37): 25.9 ± 3.0 - -
Lactulose (n=37): 27.9 ± 1.5
Stools passage (mean sum of scores)
- -
PEG 3350 (n=37): 28.5 ± 4.2 - -
Lactulose (n=37): 26.2 ± 5.1
Effectiveness (% effective)
- -
PEG 3350 (n=37): 84 - -
Lactulose (n=37): 46 p=0.002
Laxative preference (% preferred) :
- -
PEG 3350 (n=37): 73 - -
Lactulose (n=37): 27
| Additional information from study:
7 patients withdrew during the first 2-week treatment period due to lack of efficacy of the assigned intervention: 6 patients taking lactulose at time of withdrawal
Stool form scoring: 0 hard, 1 firm, 2 soft, 3 loose, 4 watery
Stool passage scoring: 0 hard, 1 difficult, 2 easy, 3 urgency, 4, no control
Stool frequency, form and easy of passage recorded by parent or guardian in symptom diary
Reviewer comments:
No definition of constipation given Baseline characteristics between groups not compared
Method of randomisation and allocation concealment not described
Non blinded study
Small sample size, no sample size calculation
No follow-up period
Intention to treat analysis not performed 15.9 % dropout rate
Results not controlled for potential confounders
Source of funding: not stated |
| Wald et al. Evaluation of biofeedback in childhood encopresis. 1987. Journal of Pediatric Gastroenterology and Nutrition 6[4], 554-558 | Study Type:
RCT
Evidence level:
1-
Study aim:
to evaluate the efficacy of biofeedback for childhood encopresis | 50 children
Inclusion criteria:
encopresis of at least 6 months of duration
Exclusion criteria:
not stated | 50 children
40 boys
Age range 6 to 15 years (mean 8.4)
Country:
USA | Intervention:
Biofeedback , one 25 to 30-minute session
Children with abnormal expulsion pattern taught a technique to normalise their patterns and they and children with normal expulsion pattern told to use the technique whenever they attempted to defecate
Reinforcement sessions at 2, 4 and 8 weeks
Comparison:
Mineral oil orally in graded amounts (range 1 to 4 tablespoons/day), designed to induce a soft bowel movement daily | Duration of treatment:
12 weeks
Assessment point (s):
Immediately after treatment completed
Follow-up period:
6 and 12 months after treatment finished
Outcome Measures:
- -
frequency of defecation - -
frequency of gross incontinence - -
frequency of staining or minor soiling - -
parental perception of clinical status and overall satisfaction
| Children in remission or markedly improved (%) (results are estimates taken from a bar chart as exact figures not reported in text)
- -
3 months: biofeedback (n=24): 54 mineral oil (n=26): 54
- -
6 months: biofeedback (n=24): 50 mineral oil (n=26): 62
- -
12 months: biofeedback (n=24): 50 mineral oil (n=26): 59
NS for any treatment period
No significant differences in outcomes for children with abnormal expulsion pattern vs. children with normal expulsion patterns | Additional information from study:
At baseline 2 groups comparable respect to age, sex, duration and severity of soiling, anorectal motility parameters and expulsion patterns
Single blinded design
Initial and follow-up office visits at 2, 4 and 8 weeks similar in duration for both groups. All outcomes recorded by parents in written calendar. Follow-up interviews by telephone performed at 3, 6 and 12 months by investigator unaware of treatment or results of anorectal studies
Based on outcomes, children placed in groups at each assessment: 1-some improvement, 2-some improvement, but major soiling (<1/week), 3-marked improvement (rare major soiling <1/week or minor soiling) 4-complete remission
2 dropouts at 3 months (1 from each group), 3 additional dropouts at 6 months (2 biofeedback) and 5 lost to follow-up at 12 months (3 biofeedback). All dropouts designated as treatment failures for each subsequent assessment point
Reviewer comments:
No clear definition of encopresis given Method of randomisation and allocation concealment not described
No sample size calculation. ITT analysis apparently performed
Unclear how the 4 outcomes groups were defined from the clinical variables
Source of funding: not stated |
| Thomson et al. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study. [erratum appears in Arch Dis Child. 2008 Jan;93(1):93]. 2007. Archives of Disease in Childhood 92[11], 996-1000 | Study Type:
RCT (cross over, multicentre)
Evidence level:
1+
Study aim:
to assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG + E) for the treatment of chronic constipation in children | 51 children
Inclusion criteria:
chronic constipation for at least 3 months
Exclusion criteria:
current or previous faecal impaction decided by either physical examination or abdominal X-ray, previous intestinal perforation/obstruction, paralytic ileus, Hirschsprung's disease, severe inflammatory conditions of the intestinal tract, severe gastroesopha geal reflux, diabetes, receiving doses of stimulant laxatives considered by local observers to be at higher end of their own doses spectrum | 51 children 29 girls mean age 5.4 years (range: 24 months to 11 years)
Country:
UK | Intervention:
PEG + E (6.9 g powder/sachet)
Comparison:
Placebo (6.9 g powder/sachet)
Washout period in between: 2 weeks
Dosing regimen for both PEG + E and placebo (number sachets/day):
- -
children aged 2 to 6 years days 1-2: 1 days 3-4: 2 (taken together) days 5-6: 3 (2 morning, 1 evening) days 7-8: 4 (2 morning, 2 evening)
- -
children aged 7 to 11 years days 1-2: 2 (taken together) days 3-4: 2 (taken together) days 5-6: 5 (2 morning, 3 evening) days 7-8: 6 (3 morning, 3 evening)
For both groups if diarrhoea, doses was decreased by 2 sachets or miss a day. If loose stools doses decreased by 1 sachet | Duration of treatment:
2 weeks each treatment period separated by a 2-week placebo washout
Assessment point (s):
immediately after each treatment period, including washout
Follow-up period:
No follow-up made after treatment completed
Outcome Measures:
Primary efficacy endpoint: - -
number of complete defecations per week
Secondary efficacy outcomes: - -
total number of defecations - -
pain on defecation - -
straining on defection - -
stool consistency - -
percentage of hard stools - -
abdominal pain on defecation - -
faecal incontinence
Adverse events
| Number of complete defecations per week (Mean (SD), range) (data do not include washout period)
ITT population - -
PEG+E (n = 47): - -
Placebo (n = 48)
PP population - -
PEG+E (n = 36): - -
Placebo (n = 36):
(95% CI, 95% confidence interval; ITT, intention to treat; PP per protocol)
Secondary efficacy outcomes, ITT population (mean, SD)
Total number of defaecations PEG+E (n = 47): 5.68 (2.771) Placebo* (n = 47): 4.10 (2.503) Treatment difference: 1.58 p Value (95% CI) = 0.003 (0.55 to 2.60)
Pain on defaecation PEG+E (n = 47): 0.49 (0.727) Placebo (n = 47): 0.77 (0.863) Treatment difference: -0.28 p Value (95% CI): 0.041 (−0.52 to − 0.01)
Straining on defaecation PEG+E (n = 47): 0.72 (0.789) Placebo (n = 47): 1.37 (1.041) Treatment difference: -0.65 p Value (95% CI): 0.001 (−0.97 to −0.33)
Stool consistency PEG+E (n = 47): 1.73 (0.497) Placebo (n = 47): 2.21 (0.556) Treatment difference: −0.48 p Value (95% CI): 0.001 (−0.68 to − 0.27)
Percentage hard stools PEG+E (n = 47): 14.64 (26.041) Placebo (n = 47): 38.19 (39.508) Treatment difference: -23.55 p Value (95% CI): <0.001
Abdominal pain on defaecation PEG+E (n = 47): 0.67 (0.789) Placebo (n = 47): 0.79 (0.903) Treatment difference: 20.12 p Value (95% CI) NS
Faecal incontinence PEG+E (n = 47): 4.70 (6.344) Placebo (n = 47): 4.85 (7.863) Treatment difference: 20.15 p Value (95% CI) NS
Mean effective dose of PEG 3350 (g/kg/day):
0.6 (2 to 6-year-old) 0.7 (7 to 11-year-old)
Adverse events:
PEG+E (31/49, 63%) Placebo (28/49, 57%) during periods I and III. None serious, most judged by investigator to be moderate or mild in severity
20 children (41%) on PEG+E: 41 events 22 children (45%) on placebo: 45 events, judged by investigator to be at least possibly related to the study treatment. Most gastro-intestinal disorders (particularly abdominal pain), PEG+E (39%, 39 events); placebo (45%, 41 events). 1 child in placebo/PEG+E group withdrawn at week 3 because of abdominal pain, assessed by investigator as being related to treatment, this child was taking placebo at the time of withdrawal. New clinically significant abnormalities on physical examination (mainly associated with faecal loading): 13 children (8/27 in the PEG+E/placebo group, 5/24 in the placebo/PEG+E group). When analysed for what these children were taking for the 2 weeks before the physical examination, 23 out of the 24 reports (95.8%) occurred when child taking placebo. Only 1 report of an abnormal abdominal examination while patient on PEG+E
Mean weight similar before and after treatment, no significant difference found between the 2 groups for change in weight while on treatment (p=0.357) | Additional information from study:
Chronic constipation defined according to Rome criteria as fewer than 3 complete bowel movements/week, and at least 1 of the following: pain on defecation on at least 25% of days; at least 25% of bowel movements with straining, and at least 25% of bowel movements with hard or lumpy stools
Random sequence group computer generated before start of recruitment using block size of 4 patients and study medication labelled accordingly. Random blocks (with numbers stored in sealed code-break envelopes) sent to investigator sites as required. As children enrolled, sites allocated treatment supplies sequentially, started with lowest possible number. Both the children (and their parents/guardians) and those administering treatment were blinded to allocation schedule
A sample size of 50 children was planned to achieve 40 evaluable children, giving 90% power to detect a true treatment difference of 0.3 bowel movements/week using a two-tailed significance test at the 5% level. As dropout rate was higher than originally estimated, recruitment target was increased to 60 children
At baseline, clinically significant abnormalities on physical examination (mainly associated with faecal loading but not impaction) recorded for 8 children (5/27 in the PEG+E/placebo group, 3/24 in the placebo/PEG+E group). Before randomisation, 47 children taking other laxatives (most frequently lactulose)
13/51 children (7/27 in the PEG+E/placebo group, 6/24 in the placebo/PEG+E group) recorded at least one deviation from the study protocol (1 child recorded 2 protocol deviations). Main reason for deviation was non-compliance with study medication (7/51 children), followed by failure to supply sufficient bowel movement data (4/51 children), and taking concomitant non-study laxative medication after randomisation (3/51 children).
Reviewer comments:
Blinding procedures not clearly described
Unclear whether outcomes assessors were also blinded to treatment allocation Study not controlled for potential confounders
Source of funding: Norgine Ltd. One of the authors was an employee of Norgine Ltd at the time the study was written. The others declared that they had nothing to declare |
| Sondheimer et al. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. 1982. Journal of Pediatric Gastroenterology and Nutrition 1[2], 223-226 | Study Type:
RCT
Evidence level:
1-
Study aim:
to compare the efficacy of mineral oil and standardised senna concentrate in the treatment of functional constipation in children | 37 children
Inclusion criteria:
patients treated for chronic functional constipation in specialist clinic
Exclusion criteria:
neurological impairment, faecal soiling in the absence of retained stool | 37 children
26 male
age range: 3 to 12 years
Country:
USA | General:
5-day course of oral bisacodyl (most patients) and daily enema for 3-5 days in addition (a minority)
Intervention:
Mineral oil orally twice daily in doses sufficient to induce loose stools and leakage of oil per rectum. After 1rst week of treatment, dose reduced until leakage ceased. This dose (range 1.5 to 5.0 cc/kg/day) maintained for minimum 3 months.
Comparison:
Senokot (tablet or syrup), doses sufficient to induce at least 1 bowel movement daily during first 2 weeks of treatment. This dose maintained for 3 months. Tapering accomplished by changing from daily to every other day and then every 3rd day medication | Duration:
Unclear, probably 6 months
Assessment point (s):
1, 3 and 6 months after initiating treatment
Follow-up period:
- -
Mineral oil group, mean 10.1 months - -
Senokot group, mean 10.5 months
Outcome Measures:
- -
daily bowel movements - -
daily soiling - -
compliance with medication
| Daily bowel movement (% patients)
at 1 month: N.S at 3 months: - -
Mineral oil (n=18): 100 - -
Senokot (n=18): 72 p<0.05
latest follow-up: - -
Mineral oil (n=18): 89 - -
Senokot (n=18): 50 p<0.05
Daily soiling (% patients)
at 1 month: - -
Mineral oil (n=18): 11 - -
Senokot (n=18): 39 p<0.05
at 3months: - -
Mineral oil (n=18): 11 - -
Senokot (n=18): 50 p<0.05
latest follow-up: - -
Mineral oil (n=18): 6 - -
Senokot (n=18): 44 p<0.05
Compliance with medication (% reliably compliant)
- -
Mineral oil (n=19): 68 - -
Senokot (n=18): 78
% successfully discontinued regular medication at latest follow-up:
- -
Mineral oil (n=18): 55 - -
Senokot (n=18): 22
an additional 33% discontinued Senokot because of unacceptable symptom control 45% in each group remained on regular medication
Episodes of symptoms recurrence /treatment/ month (Mean ± SD):
- -
Mineral oil (n=18): 0.09 ± 0.08 - -
Senokot (n=18): 0.34 ± 0.36
p<0.01 | Additional information from study:
Diagnosis of chronic functional constipation made on basis of historical features and physical exam demonstrating dilated rectum, excessive retained stool directly within anal verge and in most cases, evidence of perianal soiling
Children assigned to 1 of 2 treatment groups according to the last digit of their hospital number. All patients seen by same physician. Parents informed that 1 of 2 acceptable medications would be used to accomplish the discussed objectives
No significant baseline differences between 2 groups regarding mean age, median age at onset of symptoms and percent of patients who had received prior treatment with constipation, sex ratio, faecal soiling, overt retentive behaviour, enuresis, "difficult" toilet training and primary failure of toilet training.
Patients allowed to discontinue medications after 3 months if symptom control unsatisfactory
1 patient on mineral oil lost o follow-up after 3-month visit and not considered in results. No dropouts/lost to follow-up in other group
During 1rst month patients/parents kept records of medication, stool frequency and faecal soiling. From then on outcomes measured by telephone interviews and during consultations
Reviewer comments:
Study inadequately randomised. Allocation concealment not described Clinicians/researchers not blinded. Blinding procedures for parents/patients not clearly described
No sample size calculation performed
Results not controlled for potential confounders
Definition of “reliably compliant” not given
Source of funding: not stated |
| Bu et al. Lactobacillus casei rhamnosus Lcr35 in children with chronic constipation. 2007. Pediatrics International 49[4], 485-490 | Study Type:
RCT
Evidence level:
1+
Study aim:
to investigate the effect of Probiotics (Lactobacillus case rhamnosus, Lcr35) alone in the treatment of chronic constipation in children and to compare the effect with magnesium oxide (MgO) and placebo, respectively | 45 children
Inclusion criteria:
children under 10 years old with chronic constipation
Exclusion criteria:
organic causes of constipation like Hirschsprung's disease, spina bifida (occulta), hypothyroidis m, or other metabolic/renal abnormalities, drugs influencing gastrointestinal function other than laxatives (calcium channel blockers, antidysrythmic agents, anticonvulsivants, antidepressants, anticholinergic agents) | 45 children 23 male
Age (months, mean, SD)
MgO group
Probiotic group
Placebo group
Country:
Taiwan | Intervention:
MgO 50 mg/kg per day, twice a day
Comparison 1:
Lcr35 8 × 10^8 c.f.u/day (Antiobiophilus 250 mg, 2 capsules, twice a day)
Comparison 2:
Placebo (starch in content)
Lactulose use (1mL/kg/day) allowed when no stool passage noted for 3 days. Glycerin enema used only when no defecation for >5days or abdominal pain suffered due to stool impaction | Duration of treatment:
4 weeks
Assessment point (s):
Immediately after treatment completed
Follow-up period:
No follow up made after treatment finished
Outcome Measures:
- -
frequency of defecation - -
consistency of stools - -
episodes of soiling - -
episodes of abdominal pain - -
use of lactulose or enema
| Defecation frequency (times/day)
- -
MgO (n=18) 0.55 ± 0.13 - -
probiotic (n=18) 0.57 ± 0.17 - -
placebo (n=9) 0.37 ± 0.10
MgO vs. probiotic NS
Placebo vs. probiotic
P=0.006
MgO vs. placebo p=0.01
Hard stool (%)
- -
MgO (n=18) 23.5 ± 7.9 - -
probiotic (n=18) 22.4 ± 14.7 - -
placebo (n=9) 75.5 ± 6.1
MgO vs. probiotic NS
Placebo vs. probiotic p=0.02
MgO vs. placebo p=0.03
Abdominal pain (times)
- -
MgO (n=18) 4.8 ± 3.7 - -
probiotic (n=18) 1.9 ± 1.6 - -
placebo (n=9) 6.7 ± 3.3
MgO vs. probiotic p=0.04
Placebo vs. probiotic p=0.01
MgO vs. placebo NS
Use of glycerine enema (times)
- -
MgO (n=18) 1.3 ± 1.9 - -
probiotic (n=18) 1.6 ± 1.9 - -
placebo (n=9) 4.0 ± 2.1
MgO vs. probiotic NS
Placebo vs. probiotic p=0.04
MgO vs. placebo p=0.03
No significant differences regarding use of lactulose, faecal soiling and change of appetite amongst 3 groups
Patients with treatment success (%)
- -
MgO (n=18): 72.2 - -
probiotic (n=18): 77.8 - -
placebo (n=9): 11.1
MgO vs. probiotic NS
Placebo vs. probiotic p=0.01
MgO vs. placebo p=0.01
no adverse effects noted in probiotic and placebo groups, only 1 patient in the MgO group suffered from mild diarrhoea | Additional information from study:
Chronic constipation defined as a stool frequency of <3 times/week for >2 months and at least 1 of the following minor criteria: anal fissures with bleeding due to constipation, faecal soiling or passage of large and hard stool
Children randomly assigned into the 3 groups according to a computer -generated randomisation list
Blinding achieved by the use of 3 interventions with similar appearances and placed into identical capsules, which were either swallowed o as a whole or opened and the contents of the capsule administered in milk or fluid
Throughout the duration of study all investigators, participants and data analysts were blinded to the assigned treatment
Sample size determined by doing primary trial with 9 patients using non-inferiority to test. Equivalent margin chosen with reference to effect of active control in the data of preliminary trial. Unbalance design of allocation number used for more interest in the new drug (Lcr35): allocation rate set at 2:2:1. One sided significance level set at 0.05 and power was 80%. Under these assumptions the smallest sample size was 45 and the sample size of MgO, Lcr35 and placebo was 18, 18 and 9 respectively
No significant differences at baseline amongst the 3 group regarding: sex, age of enrolment, age of onset of constipation, duration of constipation, previous treatment, defecation period, stool consistency, abdominal pain, faecal soiling, bleeding during defecation, use of enema, taking fruit or vegetable daily
Patients asked to discontinue any laxatives previously prescribed 3 days before entering protocol, and also asked to avoid any other probiotics, yogurt or beverage containing probiotics for at least 2 weeks before treatment and during therapy
All outcomes measures recorded by parents in a stool diary
4 patients discontinued medication during study period: 2 in MgO, 1 in probiotic, 1 in placebo group (2 patients suffered from acute gastroenteritis and 2 patients lost to follow-up)
Reviewer comments:
Allocation concealment not described
Not clear whether the 2 patients who suffered from acute gastroenteritis had it as consequence of the study medication Study not controlled for potential confounders
Source of funding: not stated |
| Loening-Baucke. Polyethylene glycol without electrolytes for children with constipation and encopresis. 2002. Journal of Pediatric Gastroenterology and Nutrition 34[4], 372-377United States. | Study Type:
Prospective cohort
Evidence level:
2+
Study aim:
to determine the efficiency, acceptability, and treatment dosage of MiraLax (polyethylene glycol 3350 without electrolytes) during a 12-month treatment period in children with functional constipation and encopresis | 49 children
Inclusion criteria:
children ≥4 years of age referred for functional constipation and encopresis Functional constipation defined as delay/difficulty in defecation and encopresis (≥1/week) for more than 1 year
Exclusion criteria:
Children <4 years of age; children who refused the toilet for stooling but who had no constipation, Hirschsprung's disease, chronic intestinal pseudo-obstruction, or previous surgery of the colon or anus |
- -
Miralax group: - -
MOM group:
Country:
USA | Intervention:
MiraLax 17 dissolved in 240 mL of a beverage such as juice or Kool-Aid initial dose: 0.5 to 1 g/kg/daily
Comparison:
MOM
Initial dose:
1 to 2.5 mL/kg
Large laxative dosages divided into 2 daily doses. Parents told to adjust the dose of medication by 30 mL for MiraLax and by 7.5 mL (one-half tablespoon) for MOM every 3 days to a dosage that resulted in 1 to 2 soft bowel movements/day and prevented soiling and abdominal pain. If child retained stools despite compliance with assigned laxative, daily senna added to treatment. | Duration of treatment:
12 months
Assessment point (s):
1, 3, 6, and 12 months after initiating treatment
Follow-up period:
No follow-up made after treatment finished
Outcome Measures:
- -
bowel movement frequency - -
consistency of stools - -
soiling frequency - -
abdominal pain frequency - -
medication dosage - -
clinically significant side effects - -
compliance with medication
| Bowel movement frequency (mean, results are estimates taken form bar chart as not reported in text)
- -
baseline: - -
1 month - -
3 months - -
6 months - -
12 months
P<0.01 when comparing values at every assessment point to baseline for both treatments
Soiling frequency (mean, results are estimates taken form bar chart as not reported in text)
- -
baseline: - -
1 month - -
3 months - -
6 months - -
12 months
P<0.01 when comparing values at every assessment point to baseline for both treatments P<0.01 when comparing values between 2 groups at 1 and 12 months
Children with abdominal pain (%):
- -
baseline: - -
1 month - -
3 months - -
6 months - -
12 months
P<0.01 when comparing values at every assessment point to baseline for both treatments
Medication dosage
(Mean doses and range for children who were doing well or improved) (PEG, g/kg; MOM, mL/kg)
1 month 3 months 12 months PEG: 0.4 ± 0.1(0.1 to 0.7) MOM: only 2 children still required MOM. Their dosages were 0.4 and 1.6 mL/kg, both less than the initial treatment dosage.
mean doses for both treatments at 12 months did not differ significantly between children with or without initial palpable abdominal faecal masses. None of the patients required an increased dosage of either medication over time
5 children received a stimulant laxative in addition to PEG and 1 child received a stimulant laxative in addition to MOM (P > 0.2)
Clinically significant side effects
PEG: no significant clinical side effects. Some children had diarrhea. None of the children in the PEG group became dehydrated. Children receiving PEG and their parents did not report increased flatus, abdominal distention, or new onset of abdominal pain
Compliance with medication:
- -
PEG: No children reported disliking the taste, no parents reported that child refused to take it in juice or Kool-Aid Parental noncompliance with administering the laxative and supervising toilet use: 14% children - -
MOM: 33% children refused to take it Parental noncompliance with administering the laxative and supervising toilet use: 4% children
| Additional information from study:
Initial dose of Miralax 0.5 g/kg daily suggested for children whose rectums were loaded with stool but who had no fecal abdominal masses at the initial physical examination and no history of long intervals between huge bowel movements. Those with palpable abdominal fecal masses or history of infrequent huge bowel movements started on 1 g/kg daily
Milk of Magnesia given if family could afford only the use of a cheaper laxative or if child had previously received MOM without refusal. For these children, MOM reintroduced or adjusted to adequate dosage. Parents told how to improve the taste by mixing the child's preferred flavoring with plain MOM. Initial daily dosage of 1 mL/kg body weight suggested for children with rectal fecal masses only at initial evaluation and if no history of infrequent large bowel movements. Dosage of 2.5 mL/kg prescribed for those with fecal abdominal masses at the initial evaluation or history of huge, infrequent bowel movements.
Regular stool sittings for 5 minutes after each meal required for initial months
Patients and parents provided with diary sheets to record each outcome measured
Doing well defined as 3 or more bowel movements/week and 2 or fewer soiling episodes / month. Improved defined as 3 or more bowel movements / week and more than 75% decrease in soiling but not more than 1 soiling / week. Not doing well defined as fewer than 3 bowel movements / week, less than 75% decrease in soiling frequency, use of senna, or refusal to take the assigned laxative. Recovered defined as 3 or more bowel movements / week and 2 or fewer soiling episodes / month while not taking laxatives.
No significant baseline differences between 2 groups
Reviewer comments:
No sample size calculation performed
Outcomes for consistency of stools not reported
Not reporting on the clinically significant side effects (or lack of them) for MOM
Source of funding: Dr. Loening-Baucke recipient of grant support from Braintree Pharmaceuticals, Braintree, MA, U.S.A., for continuing studies on childhood constipation |
| Urganci et al. A comparative study: the efficacy of liquid paraffin and lactulose in management of chronic functional constipation. 2005. Pediatrics International 47[1], 15-19 | Study Type:
RCT
Evidence level:
1-
Study aim:
to determine and compare efficacy, safety and optimal dose of liquid paraffin and lactulose in children with chronic functional constipation | 40 patients
Inclusion criteria:
children 2 to 12 years old referred for evaluation of constipation with evidence of faecal impaction
Exclusion criteria:
Hirschsprung's disease, hypothyroidism, mental deficiency, chronic debilitating diseases, neurological abnormalities, previous surgery of colon | 40 patients 22 male mean age 3.7 ± 2.7 years
Country:
Turkey | Intervention:
Liquid paraffin
Comparison:
Lactulose
Medication administered orally as a suspension at 1 mL/kg, twice daily for each drug
For determination of best dose for each child, parents asked to increase or decrease the volume of each drug by 25% every 3 days as required, to yield 2 firm-loose stools per day. Maximum dose used throughout the study: 3 mL/kg per day for each drug | Duration of treatment:
8 weeks
Assessment point (s):
4 and 8 weeks after initiation of treatment
Follow-up period:
No follow-up made after treatment finished
Outcome Measures:
- -
stool consistency - -
stool frequency - -
optimal dose of drugs - -
compliance rate
| Stool consistency (mean ± SD)
- -
first 4 weeks:
last 4 weeks: Stool frequency (mean ± SD) (per week)
- -
first 4 weeks:
last 4 weeks: Optimal dose of drugs (mean ± SD) (mL/kg/day)
- -
data reported in table, assumed that for the whole study period: - -
data reported in text for the last 4 weeks of treatment:
Compliance rate (%)
- -
first 4 weeks: Liquid paraffin (n=20): 95 Lactulose (n=20): 90 N.S - -
end of 8 weeks: Liquid paraffin (n=20): 90 Lactulose (n=20): 60 p=0.02
Adverse effects:
No patient stopped treatment because of adverse effects (adverse effects not reported). During first 4 weeks, taste aversion in 1 child on liquid paraffin and abdominal distension in 2 patients on lactulose influenced compliance. During last 4 weeks, poor symptom control in 5 patients, side-effects (abdominal distension and cramping) in 3 on lactulose, and watery stools in 2 on liquid paraffin influenced compliance | Additional information from study:
Diagnosis of constipation based on symptoms of ay least 3 months duration including at least 2 of the following: hard stool, painful defecation, rectal bleeding, encopresis and < 3 bowel movements/week
Open-label randomised study
Children also met with a nutritionist, were given instructions to increase daily fibre intake to amount of gram equal to their age plus 10, parent asked to have children sit on the toilet 4 times daily after meals
Stool frequency and stool consistency recorded by parents in daily diary forms. Stool consistency scoring: 1, hard; 2, firm; 3, loose
No significant baseline differences between 2 groups
Effective treatment defined as clearance of impaction: more than 3 bowel movements/week and improvement in stool consistency
Patients considered compliant if ≥ 80% of prescribed dose taken correctly. Patients instructed to take both empty and full containers to calculate amount of medication taken
Reviewer comments:
Randomisation method not described
No sample size calculation performed
No clear definition of "evidence of faecal impaction" given
Apparently no children dropped out the study/were lost to follow-up
Study not controlled for potential confounders
Source of funding: not stated |
| Berg et al. A controlled trial of 'Senokot' in faecal soiling treated by behavioural methods. 1983. Journal of Child Psychology and Psychiatry and Allied Disciplines 24[4], 543-549 | Study Type:
Quasi RCT
Evidence level:
1-
Study aim:
to see whether behaviour therapy would suffice on its own in the treatment of severe and persistent faecal soiling or would be improved by employing a laxative as well | 44 children
Inclusion criteria:
children who had soiling as a main complaint and uncomplicate d functional faecal incontinence after an initial assessment and physical examination
Exclusion criteria:
not clearly stated | 40 children
mean age: 7.9 years (S.D. = 2.3)
gender not reported
Country:
UK | General:
Behavioural treatment, focusing on use of the toilet and freedom from soiling
Intervention:
Senokot
Comparison 1:
placebo tablets in similar dosage to Senokot
Comparison 2:
No medication
Children started on 1 tablet at night. On the next visit to the clinic, if no improvement in 'use of the toilet' and 'being clean' on the charts dosage increased to 2 tablets. Number of tablets increased to 3 on following visit if improvement had still not occurred. When soiling getting better and child using toilet dosage kept the same. Once child going regularly to toilet and not soiling tablets stopped altogether | Duration of treatment:
3 months
Assessment point (s):
3 months after starting treatment
Follow-up period:
6 months to 1 year after first entering trial (but after 3 months the study was a case series for Senokot only, therefore not reported here)
Outcome Measures:
-
severity of soiling -number of soiling-free children | Severity of soiling:
- -
At 3 months: Senokot (n=14) Placebo (n=11) No tablets (n=15)
NS between the 3 groups (outcomes not reported by group)
Number of soiling-free children
- -
Relieved (less than once/week or not at all) Senokot (n=14): 5 (35%) Placebo (n=11): 2 (18%)
- -
Not relieved Senokot (n=14): 9 Placebo (n=11): 9 NS between the 3 groups
| Additional information from study:
Children randomly allocated to 1 of 3 treatment groups, A, B and virtually in a random fashion
No significant baseline differences between the 3 groups
Psychiatrist and psychologists did not know which tablets actually contained the laxative. Tablets made up in packs labelled A and B.
Methods used in behavioural treatment: identifying targets, discussing use of rewards, star charting, reinforcement of using the toilet appropriately and staying clean, mainly by Mothers advised to avoid castigating children. Initially, children taken to toilet 3 times a day, then prompted to go unaccompanied, then expected to go on own initiative
4 children dropped out after only 1 or 2 visits
Severity of soiling rating: 0 = none, 1 = less than once a week, 2 = at least once a week but less than daily, 3 = daily
Reviewer comments:
No definitions of soiling/functional faecal incontinence given
Inadequate randomisation
Allocation concealment not described
Soiling frequently apparently assessed by interviewing parent at time of consultation
No sample size calculation performed
Not clear whether the 4 children who dropped out had already received any study medication
There is a mistake in the paper regarding outcomes for the "no tablets" groups, therefore not reported here
Results not controlled for potential confounders
Source of funding: Messrs Reckitt and Coleman provided the medication and gave their support in carrying out this trial |
Nurko et al. PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial. 2008. Journal of Pediatrics 153[2], 254-261
Nurko et al., 2008 | Study Type:
RCT (multicentre)
Evidence level:
1+
Study aim:
To establish the efficacy and best starting dose of polyethylene glycol (PEG) 3350 in the short-term treatment of children with functional constipation | 103 children
Inclusion criteria:
Children aged 4 to 16 years with chronic constipation. Patients taking other laxatives only included if they had <3 bowel movements/week while taking the laxative
Exclusion criteria:
Taking a stable dose of PEG3350, evidence of faecal impaction, guiac-positive stool, anorectal malformations , Hirschsprung's disease, myelomeningocele, hypothyroidism or other organic causes of constipation | 103 children
69 boys
mean age: 8.5 ± 3 years
Country:
USA | General:
Behavioural treatment: instructions to sit on toilet for 10 minutes twice after meals, positive reinforcement using age-appropriate printed calendars and special stickers for days without episodes of faecal incontinence and others with bowel movements
Intervention (Group 1):
Polyethylene glycol (PEG) 3350 Miralax): 0.2g/kg per day-single dose Maximum: 8.5 g per day
Comparison 1 (Group 2):
Polyethylene glycol (PEG) 3350 Miralax): 0.4g/kg per day-single dose Maximum: 17 g per day
Comparison 2 (Group 3):
Polyethylene glycol (PEG) 3350 Miralax): 0.8g/kg per day-single dose Maximum: 34 g per day
Comparison 3:
Placebo | Duration of treatment:
3 weeks
Assessment point (s):
7 and 14 days after medication started
Follow-up period:
N.A
Outcome Measures:
Efficacy:
- -
primary outcome: - -
secondary outcomes: weekly number of bowel movements weekly number of faecal incontinence episodes changes in stool consistency straining proportion of children who responded to treatment in the second week
Safety:
- -
incidence and severity of adverse effects
| Proportion of children who responded to treatment (% children)
Group 1 (n=26): 77
Group 2 (n=27): 74
Group 3 (n=26): 73
Placebo (n=24): 42
P<0.04 each group vs. placebo
P=0.026 all treatments groups vs. placebo
NS between treatment groups
Weekly number of bowel movements (BM)
Group 1 (n=26):
Before 1.7±0.9
Group 2 (n=27):
Before 1.5±1.0
Group 3 (n=26):
Before 1.5±0.5
Placebo (n=24):
Before 1.6±0.7
Overall difference between treatment groups and placebo p=0.017 P=0.015 dose-response trend
Weekly number of faecal incontinence episodes mean ± SD)
Group 1 (n=26):
Before 3.8±4.8
After 3.0±4.6
Group 2 (n=27):
Before 3.5±4.9
After 1.8±2.6
Group 3 (n=26):
Before 7.2±18.7
After 3.5±7.8
Placebo (n=24):
Before 2.4±3.8
After 1.4±3.7
NS amongst different groups
Changes in stool consistency (mean ± SD)
Group 1 (n=26):
Before 2.8±0.8
After 2.1±0.7
Group 2 (n=27):
Before 2.6±0.9
After 1.7±0.6
Group 3 (n=26):
Before 2.9±0.7
After 1.5±0.7
Placebo (n=24):
Before 3.0±0.8
After 2.4±0.9
P<0.003 each group vs. placebo
P<0.003 test for trend
P<0.003 overall difference between treatment groups
Straining scores (mean ± SD)
Group 1 (n=26):
Before 2.3±1.1
After 1.4±0.9
Group 2 (n=27):
Before 1.9±1.2
After 1.0±1.0
Group 3 (n=26):
Before 2.0±1.0
After 0.9±0.6
Placebo (n=24):
Before 2.7±1.2
After 1.5±1.2
P<0.003 each group vs. placebo
P<0.003 test for trend
P<0.003 overall difference between treatment groups
Proportion of children who responded to treatment in the second week
Group 1 (n=26): 58% (with no faecal incontinence 31%)
Group 2 (n=27): 48% (with no faecal incontinence 26%)
Group 3 (n=26): 62% (with no faecal incontinence 31%)
Placebo (n=24): 29% (with no faecal incontinence 8%)
P<0.27 group 3 vs. placebo
Incidence and severity of adverse effects
Group 1 (n=26): 9 (34.6%)
Group 2 (n=27): 16 (59.3%)
Group 3 (n=26): 17 (65.4%)
Placebo (n=24): 14 (58.3%)
NS difference amongst groups
No differences in the type of non-gastrointestinal related events, most common was headache. Higher incidence of GI-related events in patients receiving PEG vs. placebo. As dose of PEG increased, it also increased incidence of flatulence, abdominal pain, nausea and diarrhoea. No electrolyte abnormalities or differences in laboratory values amongst groups
Treatment Failures
Group 1 (n=26): 6 (4 BM frequency criteria, 2 with stool impaction)
Group 2 (n=27): 7(3 BM frequency criteria, 4 with stool impaction)
Group 3 (n=26): 7 (6 BM frequency criteria, 1 with stool impaction)
Placebo (n=24): 14 (all related to BM frequency criteria) | Additional information from study:
Chronic constipation diagnosed when for at least 3 months there was a history of <3 spontaneous bowel movements/week and ≥ 1 associated symptoms including: straining, hard stools sensation of incomplete evacuation, production of large bowel movements that may obstruct the toilet or painful defecation
Faecal impaction defined as presence of faecal hypogastric mass palpable on abdominal examination and presence of hard stool on rectal examination. diagnosis of faecal impaction made by 2 independent observers, no disagreement found in the assessment of any patient
Sample size calculation performed
Patient randomly assigned in blinded fashion in a 1:1:1:1 ratio within each participant site. Randomisation schedule at each site constructed by using random blocks of 20 patients, which provided balanced treatment assignments in order to ensure the specified treatment ratio
Miralax and placebo provided as a powder containing flavouring in identically labelled bottles reconstituted with water to 4000 mL by study personnel in the pharmacy. Dosing calculated by pharmacy staff and water added. All dose calculated to be given on a 10-mL/kg basis by pharmacy staff. The blinded research team received the reconstituted identical jugs, which were distributed to patient's parents/caregivers. No difference in colour, appearance r taste amongst different doses. Patients took single dose per day. No adjustment of study medication allowed during study. No other laxatives allowed during study
Families completed daily diary that included number and characteristics of bowel movements an documentation of episodes of faecal incontinence
Response to treatment defined as ≥3 bowel movements during the second week of treatment. Patients considered failures and withdrawn from study if they had no bowel movements (BM) for 7 days or developed faecal impaction at any point.
No significant differences in baseline characteristics between the 4 groups
14 patients did not complete the 2-week treatment:
- -
8 because of treatment failure (5 with impaction (2 Group 1, 3 Group 2), and 3 with > 7 days without a BM) (2 Group 1, 1 Group 3)] - -
3 because of adverse events (1 increased abdominal pain (placebo), 1 fever, malaise, headache (placebo), 1 exacerbation bipolar (placebo)) - -
1 withdrawal (lack of response (placebo)) - -
2 non compliance (1 Group 2, 1 Group 3) - -
3 serious adverse events occurred requiring hospitalisation (2 cases impaction, 1 case of exacerbation of bipolar/depression)
ITT analysis performed
There were no significant predictors of success by controlling for age, duration of constipation, prior laxative use, presence of stool in rectum, sex and presence of faecal incontinence at baseline
Source of funding: Supported in part by Braintree Laboratories Inc. |
