| Erickson et al. Polyethylene glycol 3350 for constipation in children with dysfunctional elimination. 2003. Journal of Urology 170[4 Pt 2], 1518-1520 | Study Type:
Retrospective case series
Evidence level:
3
Study aim:
To review the efficacy of PEG as a single agent for the treatment of constipation in children with dysfunctional elimination and asses bladder function following treatment | 46 children
Inclusion criteria:
Children diagnosed with dysfunctional voiding and constipation who received polyethylene glycol 3350 between January 2000 and July 2002
Exclusion criteria:
Known neurological impairments | 46 children
35 girls
mean age: 7.7 years (range 4.5 to 11.2 years)
11 boys
mean age: 7.6 years (range 4.4 to 11.1 years)
Country:
USA | Intervention:
Polyethylene glycol 3350 without electrolytes (MiraLax)
17 gm (1 capful) mixed with 8 ounces of fluid of parent's choice
Starting dose: 8 ounces of mixture each day with instructions to adjust the amount consumed by 1 to 2 ounces every 3 days to achieve the goal of 1 to 2 soft bowel movements per day Final dose normalised to patient weight Average final dose: 0.63 gm/kg (reported in abstract) 0.59 gm/kg (reported in text)
Comparison:
None | Duration of treatment
Mean: 194.3 days (SD 133.5)
Assessment points
Not clear
Outcome Measures:
side effects | Side effects:
- -
Diarrhoea: 9/46 children, all female
age at start of PEG (mean ± SD, years):
patients with diarrhoea (n=9):
6.8 ± 1.1
patients without diarrhoea (n=37):
8.2 ± 1.8
p=0.04
duration of follow-up (mean ± SD, days):
patients with diarrhoea (n=9):
336 ± 153
patients without diarrhoea (n=37):
108 ± 11
p=0.0028
1 child stopped taking PEG because of side effects | Additional information from study:
Diagnosis of constipation based on history of Infrequent bowel movements (less than very other day) and/or hard, large or painful bowel movements. Most children also had confirmatory abdominal x-ray demonstrating accumulation of stool in the rectum and throughout the colon
25 patients also underwent biofeedback, and 8 patients began anticholinergic medication during the course of PEG treatment
Reviewer comments:
Not clear how side effects measured in the first place
Not clear how the reviewing process was conducted
Source of funding: not stated |
| Loening-Baucke et al. Polyethylene glycol 3350 without electrolytes for the treatment of functional constipation in infants and toddlers. 2004. Journal of Pediatric Gastroenterology and Nutrition 39[5], 536-539 | Study Type:
Retrospective case series
Evidence level:
3
Study aim:
to evaluate the safety and efficacy of PEG 3350 without electrolytes for the treatment of constipation in children < 2 years of age | 75 children
Inclusion criteria:
Children with constipation <2 years of age at start of PEG therapy
Exclusion criteria:
Hirschsprung's disease, chronic intestinal pseudo-obstruction, previous surgery of colon/anus, disease states that place limitations on the act of defecation such as hypotonia, cerebral palsy and severe mental retardation | 75 children
36 boys
mean age 17 months (range 1 to 21 months)
Country:
USA | Intervention:
PEG 3350 without electrolytes (MiraLax)
Starting average dose 1g/kg body weight/day
Parents asked to adjust dose to yield 1 to 2 soft painless stools/day
Comparison:
none | Duration of treatment (months, mean ± SD)
- -
short term: 2.3 ± 1.3 (range: 1 to 4) - -
long term: 10.6 ± 8.1 (range 6 to 37)
Assessment points
- -
short term: ≤ 4 months (mean 2 months) - -
long term: ≥ 6 months (mean 11 months)
Outcome Measures:
Adverse effects | Adverse effects
a. ≤ 4 months (n=71)
5 children (7%): runny stools
(Dose of PEG (g/kg body weight/day):
Range 0.4 to 2.3
Mean 1.1 ± 1.2
Median (0.82)
b. ≥ 6 months (n=47)
1 child (2%): watery stools (he was only brought by his mother for a 6-month follow-up). The diarrhoea disappeared after lowering the dose of PEG.
(Dose of PEG (g/kg body weight/day):
Range 0.3 to 2.1
Mean 0.8 ± 0.4
Median (0.67)
Parents did not report increased flatus, abdominal distension, vomiting or new onset abdominal pain. None stopped PEG because of adverse effects.
Complete blood counts (in 24 children), electrolytes (in 9 children), renal functions (in 8 children) and liver functions (in 8 children) occasionally done in children on long-term PEG treatment, and all were within normal limits. | Additional information from study:
Constipation defined according to NASPGHAN criteria
Reviewer comments:
Authors reviewed charts from their own clinics. Not clear how the reviewing process was conducted
Not completely clear how side effects were measured in the first place, it seems that parents were asked about the at the time of consultation
Source of funding: not stated |
| Michail et al. Polyethylene glycol for constipation in children younger than eighteen months old. 2004. Journal of Pediatric Gastroenterology and Nutrition 39[2], 197-199 | Study Type:
Retrospective case series
Evidence level:
3
Study aim:
to determine safety, efficacy, and optimal dose of polyethylene glycol powder for treatment of constipation in patients younger than 18 months | 28 children
Inclusion criteria:
children younger than 18 months treated for constipation with PEG powder
Exclusion criteria:
Organic aetiology for constipation: Hirschsprung's disease, anorectal malformation, bowel obstruction, or systemic illness (hypothyroidism, cystic fibrosis, or lead poisoning associated with constipation. Taking medication that could potentially change the frequency or consistency of bowel movements | 28 children
- -
age at initiation of therapy:
gender not reported
Country:
USA | Intervention:
PEG 3350 administered orally, mixed in a ratio of 17 g to 240 mL of fluid, as recommended by the manufacturer. Caregivers for small infants mixed PEG 3350 in formula if it was the sole diet. After initial dose, families asked to titrate the dose to obtain at least one nonformed bowel movement daily. Change in dose permitted within 24 hours, if necessary
Mean initial Dose: 0.88 g/kg/day (range, 0.26–2.14 g/kg/day)
Mean effective maintenance dose: 0.78 g/kg/day (range, 0.26–1.26 g/kg/day)
Comparison:
none | Duration of treatment
Mean 6.2 ± 5 months (range, 3 weeks to 21 months)
Assessment points
at initial visit and subsequent visits every 8 to 12 weeks
Outcome Measures:
Side effects | Side effects:
Total: 5 (17.9%) of patients
1 (3.6%) infant experienced increased passage of gas per rectum
4 (14.3%) infants experienced transient diarrhoea that resolved after dose adjustment | Additional information from study:
Diagnostic criteria for functional constipation in infants and preschool children adapted from Rasquin-Weber and included: 2 weeks of hard stools (the majority of stools), or firm stools 2 or fewer times a week in the absence of structural, endocrine, or metabolic disease
No patient placed on a clean-out protocol using any other drug
Duration of therapy and side effects retrieved from the patient's chart. Information not available in the chart was obtained by telephone interview. Only 1 family needed to be contacted by telephone
Reviewer comments:
Authors reviewed charts from their own clinics. Not clear how the reviewing process was conducted
Source of funding: not stated |
| Pashankar et al. Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis. 2003. Clinical Pediatrics 42[9], 815-819 | Study Type:
Retrospective cohort
Evidence level:
2-
Study aim:
to report efficacy of PEG therapy, effective dose and patient compliance separately for children with constipation and children with constipation and encopresis over the long term | 74 children
Inclusion criteria:
children > 2 years of age with chronic constipation treated at authors' clinic daily with PEG 3350 without electrolytes (MiraLax) for > 3 months
Exclusion criteria:
history of Hirschsprung's disease, anorectal malformations, abdominal surgery, or any systemic illness leading to constipation | 74 children 40 boys
mean age:
- -
constipation only: 6.6 years (range 2 to 16.9) - -
constipation and encopresis: 8.4 years (4.3 to 12.8)
Country:
USA | Intervention:
PEG 3350 without electrolytes (MiraLax)
0.8 g/kg/day administered orally, as recommended by the manufacturer mixed in a ratio of 17 g of powder to 240 mL of water or other beverage. Families allowed free choice of beverage
Parents asked to adjust the dose as required to yield 2 soft painless stools per day
Comparison:
Behaviour modification programme | Duration of treatment
Mean 8.4 months (range 3 to 30)
Assessment points
Unclear
Outcome Measures:
Adverse effects | Average dose of PEG at time of evaluation:
0.73 g/kg/day (range 0.3 to 1.8) following adjustment of dose by caretakers
Adverse effects:
no major clinical adverse effects observed | Additional information from study:
Diagnosis of chronic constipation based on symptoms of at least 3 months' duration including at least 2 of the following: hard stools, painful defection, encopresis or fewer than 3 bowel movements/week
Encopresis defined as constipation with involuntary loss of stools into the underwear beyond a developmental age of 4 years
Reviewer comments:
Authors reviewed charts from their own clinics. Not clear how the reviewing process was conducted. Some outcomes variables gathered by interviewing patients/parents and examining patients. Unclear how data on adverse effects were obtained
Source of funding: Financial assistance provided in part by Braintree Laboratories, Braintree, MA |
| Pashankar et al. Safety of polyethylene glycol 3350 for the treatment of chronic constipation in children. 2003. Archives of Pediatrics and Adolescent Medicine 157[7], 661-664 | Study Type:
Prospective case series
Evidence level:
3
Study aim:
to assess the biochemical and clinical safety profile of long-term PEG 3350 treatment in a large cohort of children and also paediatric patient acceptance of long-term PEG therapy | 83 children
Inclusion criteria:
Children > than 2 years old with chronic constipation who were treated daily with PEG >3 months
Exclusion criteria:
history of Hirschsprung's disease, anorectal malformations, or any systemic illness potentially leading to constipation | 83 children
Male/female:
48/35
Mean age 7.4 years (range 2.0 to 16.9 years)
Country:
USA | Intervention:
PEG 3350 without electrolytes (MiraLax)
Initial dose: 0.8 g/kg per day According to manufacturer's directions, parents instructed to dissolve 17 g of PEG powder in 240 mL of water or other beverage and to give prepared solution in 2 divided doses. Families allowed choice of beverage to suit child's preference. Parents asked to adjust dose of PEG solution as required to yield 2 soft painless stools per day. Over time, parents instructed to gradually decrease dose of PEG if symptoms of constipation and encopresis showed improvement
Comparison:
None | Duration of treatment
mean 8.7 months (range, 3 to 30 months
Assessment points
Outcome Measures:
Adverse effects:
- -
clinical - -
laboratory
| Clinical adverse effects
Minor and acceptable over mean duration of therapy
8 patients (10%): frequent watery stools sometime during therapy. Diarrhoea disappeared with reduction of dose
5 children (6%): bloating or flatulence
2 children (2%): abdominal pain
1 patient each (1%): thirst, fatigue, and nausea after receiving PEG solution on an empty stomach
None of the patients stopped treatment due to adverse effects and all were to continue PEG therapy.
General physical examination findings revealed no new significant abnormalities compared with the pre-treatment
Laboratory evaluation results:
Haemoglobin, haematocrit, serum electrolytes, blood urea nitrogen, serum creatinine, serum albumin, and osmolality, normal in all patients (10 patients did not have serum osmolality measured)
9 patients (11%) had slightly elevated ALT level (<1.5 times the upper limit of normal; range, 31 to 45 U/L). 8 of these patients had ALT levels remeasured within 8 weeks, 7 of whom still receiving PEG therapy. 7 of these 8 patients had values in the reference range, 1 had slightly elevated ALT level (<1.2 times normal; 28 U/L).
3 patients (4%) had an elevated aspartate aminotransferase level (<1.5 times normal; range, 42-52 U/L), and all had normal values when remeasured while still receiving PEG therapy
Dose and duration of PEG therapy not significantly different in patients with abnormal values compared with those with laboratory values in the reference range | Additional information from study:
Diagnosis of chronic constipation based on symptoms of at least 3 months' duration, including at least 2 of the following: hard stools, painful defecation, encopresis, or fewer than 3 bowel movements per week
All other laxative treatments stopped before starting PEG
Parents interviewed using structured questionnaire and asked about dose of PEG given, medication compliance, any possible adverse effects of PEG, and particularly about excessively loose or frequent stools, abdominal pain, flatulence, bloating, and nausea. Parents asked about overall improvement in bowel movement pattern regarding stool frequency and consistency with PEG therapy. Following interview and physical examination, 4 mL of blood obtained for measurement of different parameters
Results of blood tests considered abnormal if outside (even by 1 point) the age- and sex appropriate reference range established in authors' hospital. If results abnormal, blood tests repeated within 8 weeks while patient continued to receive therapy
Source of funding: Study financially assisted by Braintree Laboratories |
| Clark et al. Serum beta-carotene, retinol, and alpha-tocopherol levels during mineral oil therapy for constipation. 1987. American Journal of Diseases of Children 141[11], 1210-1212 | Study Type:
Prospective case series
Evidence level:
3
Study aim:
to prospectively monitor children receiving large doses of mineral oil throughout the early phase of treatment | 25 children
Inclusion criteria:
Children with encopresis, over 1 year old with no previous treatment with mineral oil
Exclusion criteria:
not stated | 25 children
mean age: 7.83 years (range 1.75 to 14.27 years)
gender not reported
Country:
USA | Intervention:
Following initial disimpaction (not reported with what) , mineral oil, 45 mL twice daily between meals
Dose gradually decreased on monthly basis (usually 30 mL/mo) depending on patient's reported performance and results of serial rectal examinations
- -
Mean ± SEM: Month 1: 4.0 ± 1.4 Month 2: 2.9 ± 1.2 Month 3: 2.1 ± 0.5 Month 4: 1.4 ± 0.4
Comparison:
none | Duration of treatment
4 months
Assessment points
1, 2, 3 and 4 months
Outcome Measures:
Serum beta-carotene level
Retinol level
Alfa tocopherol level | Serum levels (micromols/L (micrograms/dL) (mean ± SEM):
- -
Month 1 (n=25): Serum beta-carotene:
Retinol: NS as compared to baseline
- -
Month 2 (n=17): Serum beta-carotene:
Retinol: NS as compared to baseline
- -
Month 3 (n=10): Serum beta-carotene:
Retinol:
Baseline: 1.48 ± 0.84 (42.3 ± 24.1)
Treatment: 2.22 ± 0.77
(63.5 ± 22.1) P<0.01
- -
Month 4 (n=5):
Retinol: NS as compared to baseline
Serum alfa tocopherol levels remained relatively unchanged throughout study. No statistical significant difference between baseline levels and those obtained throughout the 4 months of therapy | Additional information from study:
Vitamin supplementation not prescribed
Normal serum values for authors' laboratory:
- -
Serum beta-Carotene: >0.6 micromols/L (>30 micrograms/dL) - -
Retinol: 0.70 micromols/L (20 micrograms/dL) - -
Alfa tocopherol: >9 micromols/L (>0.4 micrograms/dL)
Since number of patients returning for subsequent visits gradually decreased, basal levels were recalculated for each month of treatment using the remaining patients as their own controls
Source of funding: not stated |
| Hardikar et al. Macrogol 3350 plus electrolytes for chronic constipation in children: a single-centre, open-label study. 2007. Journal of Paediatrics and Child Health 43[7-8], 527-531 | Study Type:
Prospective case series
Evidence level:
3
Study aim:
To evaluate the safety and efficacy of a macrogol 3350-based electrolyte containing preparation in the treatment of chronic constipation in children | 81 children
Inclusion criteria:
Children aged 24 months to 11 years with chronic constipation for at least 6 months, which was either untreated or inadequately treated by laxatives
Exclusion criteria:
children treated for faecal impaction with bowel washouts during the previous 2 months, or had a past history of intestinal perforation/ob struction, Hirschsprung's disease, paralytic ileum, toxic megacolon, severe inflammation of the intestinal tract, urinary tract infection,, uncontrolled renal, hepatic or cardiac diseases, endocrine disorders, or any other severe unstable coexisting disease during the previous 30 days | 77 children
44% boys mean age:
4.9 ± 2.6 years
Country:
Australia | Intervention:
Macrogol 3350 plus electrolytes (Movicol)
Each sachet (6.563 g Macrogol) dissolved 62.5 mL of water
Number of sachets first 5 days
- -
Children aged 2 to 6 years:
- -
Children aged 7 to 11 years
Thereafter and until end of study dosage titrated according to faecal form. This dose increased by 1 sachet/day in the event of continued hard stools/no bowel movements, and decreased by 1 to 2 sachets/day in the event of loose stools or diarrhoea
Comparison:
None | Duration of treatment
Mean 75.5 days
Assessment points
Adverse effects monitored throughout the study, venous samples for laboratory taken at baseline, 28 days and 84 days. Vital signs measured at baseline and 84 days
Outcome Measures:
- -
Safety :
adverse effects
laboratory tests
changes in vital signs | Mean numbers of sachets/day during treatment period:
1.3 (6.9 g)
Adverse effects (n=78)
72 children (92%) reported a total of 318 events
241 (76%) assessed as unrelated to study treatment
262 (82%): mild
302 (95%): resolved by end of study
6 serious adverse events in 4 children: 4 affected gastrointestinal system. All assessed by investigator as unrelated or unlikely to be related to study medication and resolved at end of study. 1 serious adverse event (faecal impaction) led to patient's premature withdrawal from study as child was admitted as impatient for bowel washout
Changes in vital signs:
No clinically significant changes as result of study medication | Additional information from study:
Chronic constipation defined as fewer than 3 complete bowel movements per week over previous14 days in association with either straining or passage of hard stools in at least a quarter of bowel movements
If investigator considered it to be clinically necessary patients could be given another laxative provided they had failed to respond to the maximum dose for 3 days
No other therapeutic interventions, including an increase in oral fluids or dietary fibre were instituted
Any child who developed faecal impaction (faecal loading) which required treatment was withdrawn from study and classified as treatment failure
78 (96%) patients included in safety analysis.
65 (80%) patients completed study. 16 patients withdrew prematurely: 6 unable or refused to take medication, 4 protocol deviation, 3 poor compliance, 1 failed to return for final visit, 1 parent refused to give medication, 1 serious adverse effect
Reviewer comments:
6 serious adverse events in 4 children: 4 affected gastrointestinal system, remaining 2 not reported
Not clear how clinical adverse effects were asked for
Source of funding: Movicol sachets supplied by Norgine Ltd. Uxbridge, UK. Study supported by a research grant from Norgine Ltd. Uxbridge, UK and Norgine PTY, Sydney, Australia |
| 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
Outcome Measures:
- -
optimal dose of drugs - -
compliance rate
| 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
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 at least 3 months duration including at least 2 of the following: hard stool, painful defecation, rectal bleeding, encopresis and fewer
Open-label randomised study
Children also met with a nutritionist, were given instructions to increase daily fibre intake to amount of grams 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
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 |
| 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:
ambulatory children with constipation despite their usual dietary treatment for at least 1 month, aged 6 months to 3 years
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–75th percentiles)
- -
PEG 4000: 28 (19.5–33.7) - -
Lactulose: 25.8 (12.3–33)
Country:
France | Intervention:
PEG 4000
-Comparison:
Lactulose
-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 was only allowed twice during the study, If child produced liquid stools for more than 1 day or more than 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 Outcome Measures:
- -
Biological tolerance: ion electrolytes total protein albumin vitamin A vitamin D folates
- -
Clinical tolerance: body height body weight adverse effects
| 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): PEG 4000: 1 (1 to 2) Lactulose: 2 (1 to 6) P<0.05
- -
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-month 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 <1 stool/day for >1 month in children 6 to 12 months old and <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 the amendment was applied. 2 children in PEG 4000 group dropped out before any study drug intake, so the intention to treat (ITT) 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 1 major deviation, 11 in the PEG 4000 group and 9 in the lactulose group. Reasons for exclusion were no laboratory test at D84, 1 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). There were no clinically relevant differences between the 2 treatment groups at baseline for clinical or biologic parameters.
Stool frequency, abdominal pain, vomiting, and nausea recorded by parents 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 (age and gender not reported)
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
Outcome Measures:
- -
adverse effects
| Adverse effects (n patients):
senna week: 12 (8 colic, 1 diarrhoea, 2 colic+ diarrhoea, 1 colic + distension) no treatment week: 4 (3 colic, 1 colic + distension) 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:
Very small sample size, no sample size calculation
Inadequate method of allocation concealment
Patients' baseline characteristics not reported
Study probably non 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 |
| 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/ob struction, paralytic ileus, Hirschsprung's disease, severe inflammatory conditions of the intestinal tract, severe gastroesophageal 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, dose was decreased by 2 sachets or miss a day. If loose stools dose 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
Outcome Measures:
Adverse events | 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 < 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 1 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)
Safety monitored by adverse events recording, physical examination findings, and weight changes
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 |
| 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
Outcome Measures:
- -
optimal dose of drug - -
side effects
| Optimal dose of drug
- -
Final effective dose (mean, ml/kg/day): Liquid paraffin (n=127) 1.72 ± 0.13 Lactulose (n=120) 2.08 ± 0.21 p<0.001
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)
Abdominal pain: 50
Bad palatability: 40
Pain at defecation: 50
Bloating: 20
Diarrhoea: 30
Anal oil leakage: 40
Flatulence: 20
Nausea: 5
Hard stool: 6
Vomiting: 0 | Additional information from study:
Diagnosis of chronic functional constipation based on having at least 2 of the following symptoms for the last 3 months: <3 bowel movements/week, faecal soiling >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 < 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
Parents received chart to record side effects
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 confounders
Source of funding: not stated, but authors reported “no conflicts of interests” |
| 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/anus |
- -
Miralax group: 28 children 20 boys Mean age ± SD: 8.7 ± 3.6 years Range 4.1 to 17.5 years - -
MOM group: 21 children 17 boys Mean ± SD: 7.3 ± 3.0 years Range: 4.0 to 13.9 years
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
Outcome Measures:
- -
medication dosage - -
clinically significant side effects - -
compliance with medication
| Medication dosage
(Mean doses and range for children who were doing well or improved) (PEG, g/kg; MOM, mL/kg)
1 month
PEG:
0.6 ± 0.2 (0.3 to 1.1)
MOM:
1.4 ± 0.6 (0.6 to 2.6)
3 months
PEG:
0.6 ± 0.3 (0.3 to 1.4 )
MOM:
1.2 ± 0.5 (0.6 to 2.4)
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 diarrhoea. None of the children in the PEG group became dehydrated. Children receiving PEG and their parents did not report increased flatus, abdominal distension, 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 an adequate dosage. Parents told how to improve the taste by mixing the child's preferred flavouring with plain MOM. Initial daily dosage of 1 mL/kg body weight suggested for children with rectal faecal masses only at initial evaluation and if they had no history of infrequent large bowel movements. Dosage of 2.5 mL/kg prescribed for those with faecal 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
Global assessment of whether child was “doing well,” “improved,” or “not doing well” was recorded. 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 a more than 75% decrease in soiling but not more than 1 soiling / week. Not doing well was defined as fewer than 3 bowel movements / week, a 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 |
| 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
Outcome Measures:
- -
safety profile - -
patient's acceptance and compliance
| 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 < 0.001)
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)
1 month: 1.2 ± 0.7
3 months: 1.2 ± 0.8
additional senna at some point: 1 child
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
It was estimated that 38 subjects were 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 0.05 significance level with 0.80 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
Patients and parents questioned with respect to side effects during each visit
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 |
| Adler. Effective Treatment of Constipation and Encopresis with Movicol (Macrogol 3350 with Electrolytes) in Children and Adolescents. 2005. Gut 54[Suppl VII], A217 Adler, 2005 | Study Type:
Prospective Case series
Evidence level:
3
Study aim:
to assess the effectiveness of Movicol (macrogol 3350 with electrolytes), over the course of long term treatment in children with constipation | 134 patients
Inclusion criteria:
children referred with constipation and/or encopresis to The Queen Silvia Children's Hospital, Sweden
Exclusion criteria:
Not stated | 134 patients 88 males age not clearly reported
Country:
Sweden | Intervention:
Movicol (macrogol 3350 with electrolytes,13.8g sachets )
- -
Mean starting dose:
Doses adjusted in each patient to achieve symptom relief with the minimally effective dosage
Comparison:
None | Duration of treatment:
Mean: 50 weeks (SD ±50 weeks; range 1 to 211 weeks)
Assessment point (s):
unclear
Outcome Measures:
- -
final treatment dose - -
side effects
| Mean dose at end of observational period
Age 2 to 6: 0.42 sachets
Age 7 to 11: 0.49 sachets
- -
overall mean change: 0.553 to 0.477 sachets/day
Side-effects were reported in 10 (7.5%) patients and these were generally mild and transient | Reviewer's' comments
It is difficult to assess the quality criteria and to make comments on this study because we have only been able to review the abstract. This abstract was included because it provides some evidence on long-term treatment with Movicol
Source of funding: Not stated |
