Comparison of Efficacy & Tolerability Of PEG 4000 Versus PEG 3350+ Electrolytes for Pediatric Fecal Disimpaction

Summary

Childhood constipation is a common but serious gastrointestinal disorder prevalent worldwide. In 90-95% of children, it is of functional origin. Thirty to seventy-five percent of children with functional constipation also have fecal impaction. The treatment strategy for functional constipation includes fecal disimpaction and maintenance therapy to ensure regular bowel movements. Polyethylene glycol (PEG) based laxatives have been recommended as the first-line therapeutic agents. The commonly used formulations are PEG 3350 with a molecular weight between 3200- 3700 g/mol and PEG 4000 with molecular weight of 4000 g/mol. Both are shown to be effective in pediatric constipation management in placebo-controlled trials. PEG 3350 + Electrolyte (E) is more widely used than PEG 4000 for the management of constipation. This might be because of the perception that PEG 3350 + E is safer in terms of preventing electrolyte imbalance. However, because of the inclusion of electrolytes, PEG 3350+ E solution taste saltier than PEG 4000. Many patients struggle to tolerate the unpleasant taste resulting in the high incidence of non-compliance. To date, no pediatric trials have compared PEG 4000 versus PEG 3350+E for management of Fecal disimpaction. Present study has been planned to evaluate the efficacy \& tolerability of PEG 4000 versus PEG 3350+ E for fecal disimpaction in pediatric functional constipation. Patients between age 1-16 years having functional constipation (as per ROME IV criteria) with fecal impaction will be included. Subjects will be randomly assigned to either PEG 4000 or PEG 3350+E at a ratio of 1:1. They will be stratified into 3 different age groups: 1-5 years, 6-11 years, and 12-16 years. They will receive either of the PEG solutions (as per allocation) at a dose of 1.5 gm/kg/day for 6 consecutive days or till the resolution of fecal impaction whichever is earlier. The resolution of fecal impaction is defined as the passage of clear liquid stool and the disappearance of palpable abdominal fecolith. Primary outcome is defined as the proportion of subjects achieving fecal disimpaction in each arm. Secondary outcomes are defined as follows: 1. Total no of Days required to achieve fecal disimpaction in each arm 2. Cumulative dose of PEG required for fecal disimpaction in each arm 3. Proportion of subjects (\> 5 years age) reporting palatability issues in each arm 4. Proportion of subjects discontinuing the treatment due to palatability issues in each arm

Timeline

Start

2024-04-15

Primary completion

2024-09-15

Completion

2024-09-15

Publications

• Results Benninga MA, Voskuijl WP, Taminiau JA. Childhood constipation: is there new light in the tunnel? J Pediatr Gastroenterol Nutr. 2004 Nov;39(5):448-64. doi: 10.1097/00005176-200411000-00002. No abstract available.
• Results Rubin G, Dale A. Chronic constipation in children. BMJ. 2006 Nov 18;333(7577):1051-5. doi: 10.1136/bmj.39007.760174.47. No abstract available.
• Results van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. Am J Gastroenterol. 2006 Oct;101(10):2401-9. doi: 10.1111/j.1572-0241.2006.00771.x.
• Results Tran DL, Sintusek P. Functional constipation in children: What physicians should know. World J Gastroenterol. 2023 Feb 28;29(8):1261-1288. doi: 10.3748/wjg.v29.i8.1261.
• Results Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, Walker LS. Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology. 2006 Apr;130(5):1527-37. doi: 10.1053/j.gastro.2005.08.063.
• Results Shatnawi MS, Alrwalah MM, Ghanma AM, Alqura'an ML, Zreiqat EN, Alzu'bi MM. Lactulose versus polyethylene glycol for disimpaction therapy in constipated children, a randomized controlled study. Sudan J Paediatr. 2019;19(1):31-36. doi: 10.24911/SJP.106-1546805996.
• Results Tabbers MM, DiLorenzo C, Berger MY, Faure C, Langendam MW, Nurko S, Staiano A, Vandenplas Y, Benninga MA; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; North American Society for Pediatric Gastroenterology. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014 Feb;58(2):258-74. doi: 10.1097/MPG.0000000000000266.
• Results Alper A, Pashankar DS. Polyethylene glycol: a game-changer laxative for children. J Pediatr Gastroenterol Nutr. 2013 Aug;57(2):134-40. doi: 10.1097/MPG.0b013e318296404a.
• Results Treepongkaruna S, Simakachorn N, Pienvichit P, Varavithya W, Tongpenyai Y, Garnier P, Mathiex-Fortunet H. A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the treatment of constipation in children. BMC Pediatr. 2014 Jun 19;14:153. doi: 10.1186/1471-2431-14-153.
• Results Candy DC, Edwards D, Geraint M. 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. J Pediatr Gastroenterol Nutr. 2006 Jul;43(1):65-70. doi: 10.1097/01.mpg.0000228097.58960.e6.
• Results Youssef NN, Peters JM, Henderson W, Shultz-Peters S, Lockhart DK, Di Lorenzo C. Dose response of PEG 3350 for the treatment of childhood fecal impaction. J Pediatr. 2002 Sep;141(3):410-4. doi: 10.1067/mpd.2002.126603.
• Results Bekkali NL, van den Berg MM, Dijkgraaf MG, van Wijk MP, Bongers ME, Liem O, Benninga MA. Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG. Pediatrics. 2009 Dec;124(6):e1108-15. doi: 10.1542/peds.2009-0022.
• Results Miller MK, Dowd MD, Friesen CA, Walsh-Kelly CM. A randomized trial of enema versus polyethylene glycol 3350 for fecal disimpaction in children presenting to an emergency department. Pediatr Emerg Care. 2012 Feb;28(2):115-9. doi: 10.1097/PEC.0b013e3182442c0a.
• Results Seinela L, Sairanen U, Laine T, Kurl S, Pettersson T, Happonen P. Comparison of polyethylene glycol with and without electrolytes in the treatment of constipation in elderly institutionalized patients: a randomized, double-blind, parallel-group study. Drugs Aging. 2009;26(8):703-13. doi: 10.2165/11316470-000000000-00000.
• Results Chaussade S, Minic M. Comparison of efficacy and safety of two doses of two different polyethylene glycol-based laxatives in the treatment of constipation. Aliment Pharmacol Ther. 2003 Jan;17(1):165-72. doi: 10.1046/j.1365-2036.2003.01390.x.
• Results Szojda MM, Mulder CJ, Felt-Bersma RJ. Differences in taste between two polyethylene glycol preparations. J Gastrointestin Liver Dis. 2007 Dec;16(4):379-81.
• Results Katelaris P, Naganathan V, Liu K, Krassas G, Gullotta J. Comparison of the effectiveness of polyethylene glycol with and without electrolytes in constipation: a systematic review and network meta-analysis. BMC Gastroenterol. 2016 Mar 31;16:42. doi: 10.1186/s12876-016-0457-9.
• Results Bekkali NLH, Hoekman DR, Liem O, Bongers MEJ, van Wijk MP, Zegers B, Pelleboer RA, Verwijs W, Koot BGP, Voropaiev M, Benninga MA. Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):10-15. doi: 10.1097/MPG.0000000000001726.
• Results Savino F, Viola S, Erasmo M, Di Nardo G, Oliva S, Cucchiara S. Efficacy and tolerability of peg-only laxative on faecal impaction and chronic constipation in children. A controlled double blind randomized study vs a standard peg-electrolyte laxative. BMC Pediatr. 2012 Nov 15;12:178. doi: 10.1186/1471-2431-12-178.
• Results Boles EE, Gaines CL, Tillman EM. Comparison of Polyethylene Glycol-Electrolyte Solution vs Polyethylene Glycol-3350 for the Treatment of Fecal Impaction in Pediatric Patients. J Pediatr Pharmacol Ther. 2015 May-Jun;20(3):210-6. doi: 10.5863/1551-6776-20.3.210.

Drugs

Indications