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Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

ABSTRACT: OBJECTIVE:The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350?+?E) compared to PEG4000 without electrolytes (PEG4000). METHODS:In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350?+?E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ?1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ?3 per week with <1 episode of fecal incontinence. RESULTS:Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350?+?E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350?+?E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P?=?0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS:Noninferiority regarding long-term constipation-related symptoms of PEG3350?+?E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.

SUBMITTER: Bekkali NLH

PROVIDER: S-EPMC5753830 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

Bekkali Noor L H NLH Hoekman Daniël R DR Liem Olivia O Bongers Marloes E J MEJ van Wijk Michiel P MP Zegers Bas B Pelleboer Rolf A RA Verwijs Wim W Koot Bart G P BGP Voropaiev Maksym M Benninga Marc A MA

Journal of pediatric gastroenterology and nutrition 20180101 1

<h4>Objective</h4>The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000).<h4>Methods</h4>In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to recei ...[more]

PMID: 28906317

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Project description:IMPORTANCE:Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades. OBJECTIVE:To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose. DESIGN, SETTING, AND PARTICIPANTS:The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE. INTERVENTIONS:Participants were block randomized to receive treatment with PEG, 4-L dose (n?=?25), or standard-of-care lactulose (n?=?25) during hospitalization. MAIN OUTCOMES AND MEASURES:The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay. RESULTS:A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P?<?.01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P?=?.002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P?=?.01). Adverse events were uncommon, and none was definitely study related. CONCLUSIONS AND RELEVANCE:PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01283152.

Project description:Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC. Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC. Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6–48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with “response” defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints. Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55–31.49%) and 11.03% (CI −5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036). Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC. Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02751411.

Project description:Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention.Trial registrationClinicalTrials.gov NCT00828984.

Dataset Information

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

Publications

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

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