This double-blind randomized clinical trial was conducted on the children aged 4-15 years with FC, as defined by the Rome IV Criteria (Table 1) (14,15), who were visited in an outpatient pediatric clinic affiliated to Shiraz University of Medical Sciences between February and July 2021. During this period, 120 patients were eligible for participation in the study. The enrolled patients (n=80) who met the inclusion criteria were randomly assigned to the study groups using block randomization with the block size of 8 (the list blocks were extracted from www.sealedenvelope.com). Group A included the children who received single-dose PEG and group B included the children who received PEG in divided doses. It is worth mentioning that the investigator and the patients were kept blind to the study groups.
Setting and participants
In case the study participants had severe stool impaction, they underwent rectal disimpaction by paraffin and N/S enema and then, PEG was started. The drug was administered orally at a dose of 1 cc/kg body weight from a solution containing 40% PEG without electrolytes (0.4 g/kg) on a daily basis. Increasing the dose up to 2 cc/kg body weight (0.8 g/kg) daily was allowed by the caregiver for the children who did not improve after at least three days of treatment. It should be noted that the use of other laxatives was not allowed during the study period. In addition, if the patients did not defecate for more than three days, they were referred to a physician. A proper toilet training with regular stool sittings for 5-10 minutes was advised after each meal. Furthermore, the patients and their parents were asked to keep a stool diary during the 12 weeks of treatment, with weekly reports of the frequency of bowel movements, stool consistency measured through the Bristol Stool Form Scale (BSFS) (Picture 1) (16), episodes of fecal incontinence, and presence of the associated gastrointestinal symptoms such as nausea, vomiting, flatulence, abdominal pain, painful defecation, and rectal bleeding.
Patients’ follow-up and outcomes
Follow-up visits were scheduled at 1, 3, 6, and 12 weeks after enrollment. At each visit, the interim history was assessed, stool diaries were reviewed and discussed, and a physical examination was done. Clinical progress, compliance with the treatment program, stool frequency, stool consistency, episodes of fecal incontinence, and occurrence of abdominal pain and other possible gastrointestinal symptoms were assessed, as well. The primary outcome measure was the improvement of constipation defined as ˃2 bowel movements per week, ≥2 stool consistency grade on BSFS, and absence of fecal incontinence, abdominal pain, pain on defecation, and rectal bleeding. The secondary outcome measure was the improvement of other associated gastrointestinal symptoms such as nausea, vomiting, and flatulence.
At first, the necessary arrangements were made with the Pediatrics Department of Shiraz University of Medical Sciences to access the cases. All the children aged 4-15 years who were referred to the pediatric clinics of Shiraz University of Medical Sciences due to suffering from FC were eligible for the study. The diagnosis of FC was made by the Rome IV Criteria (Table 1). The inclusion criteria of the study were aging 4-15 years, suffering from FC based on the Rome IV criteria, and having complete information and follow-up. The exclusion criteria were non-compliance with the treatment, having organic causes of constipation including Hirschsprung disease, spinal bifida (occulta), and hypothyroidism, suffering from other metabolic renal abnormalities, mental retardation, and other organic problems, being suspicious for bowl obstruction, and having used lactulose or other laxatives, prebiotics, or probiotics within four weeks prior to the first visit.
Based on a pilot study reporting the mean of BSFS among 30 patients and considering the effect size of 0.60, power of 80%, type 1 error of 5%, and drop-out rate of 10%, a 40-subject sample size was estimated for each study group. Totally, 80 patients were randomly assigned to the study groups.
In this study, continuous variables were reported as mean and standard deviation, and the comparisons between and within the study groups were made using independent sample t-test and paired sample t-test, respectively. Categorical variables were presented as number and percentage, and the comparisons between the groups were made through chi-square and Fisher’s exact test. Moreover, repeated measures ANOVA was used to compare the two groups over time. All data analyses were done using the Statistical Package for Social Sciences (SPSS Inc., Chicago, version 23) and p<0.05 was considered statistically significant.
Human dignity, preservation of individuals’ medical secrets, and commitment to Helsinki Ethics were respected throughout the study. Written informed consent forms for using the patients’ information were completed by either the patients or their parents. The executive protocol of the study was confirmed by the Ethics Committee of Shiraz University of Medical Sciences and investigation of the cases was conducted in the pediatric clinics affiliated to Shiraz University of Medical Sciences (IR.SUMS.MED.REC.1397.498). This study has also been accepted by Iranian Registry of Clinical Trials by the code IRCT20090908002434N9.