Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)

Summary

Hepatic Encephaopathy is a common complication occurring in patients with Liver cirrhosis. Patients usually develop mild confusion, sleep disturbance or obtundation. It occurs due to accumulation of excess ammonia in the brain, as the liver is unable to metabolize the ammonia. The common gold standard treatment recommended for patients with Hepatic Encephalopathy is Lactulose syrup. This is a non absorbable sugar, often combined with an antibiotic called Rifaxamine to treat this condition. Polyethylene glycol is in a class of medications called osmotic laxatives which works by causing water to be retained with the stool. PEG and lactulose, when used together, result in faster resolution of symptoms suggesting that PEG may be superior to standard lactulose therapy in these patients. Non-absorbable sugars like lactulose are associated with non-serious (mainly gastrointestinal) adverse events like diarrhea and bloating Hence, due to the side effect profile, newer drugs continue to be tested for treatment of Hepatic Encephalopathy. The aim of this research project is to compare the effect of PEG versus lactulose for treatment of HE in patients with liver cirrhosis. The investigators want to compare the resolution of HE as the main outcome. In addition, they will compare length of stay, non-serious (mainly gastrointestinal) adverse events, and 3 months outcome. The investigators hypothesize that rapid purgation of the gut using PEG may resolve HE more effectively than lactulose.

Timeline

Start

2020-03-09

Primary completion

2023-12-30

Completion

2023-12-30

Publications

• Background Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25 Suppl 1:3-9. doi: 10.1111/j.1746-6342.2006.03215.x.
• Background Rahimi RS, Rockey DC. Novel Ammonia-Lowering Agents for Hepatic Encephalopathy. Clin Liver Dis. 2015 Aug;19(3):539-49. doi: 10.1016/j.cld.2015.04.008. Epub 2015 May 30.
• Background Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med. 1969 Aug 21;281(8):408-12. doi: 10.1056/NEJM196908212810803. No abstract available.
• Background Sharma P, Sharma BC, Sarin SK. Predictors of nonresponse to lactulose in patients with cirrhosis and hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2010 May;22(5):526-31. doi: 10.1097/MEG.0b013e3283341b7d.
• Background Tapper EB, Jiang ZG, Patwardhan VR. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy. Mayo Clin Proc. 2015 May;90(5):646-58. doi: 10.1016/j.mayocp.2015.03.003. Epub 2015 Apr 9.
• Background Romero-Gomez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galan JJ, Montoliu C, Baccaro E, Guevara M, Cordoba J, Soriano G, Navarro JM, Martinez-Sierra C, Grande L, Galindo A, Mira E, Manes S, Ruiz A. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med. 2010 Sep 7;153(5):281-8. doi: 10.7326/0003-4819-153-5-201009070-00002.
• Background Jain L, Sharma BC, Sharma P, Srivastava S, Agrawal A, Sarin SK. Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy. Dig Liver Dis. 2012 Dec;44(12):1027-31. doi: 10.1016/j.dld.2012.07.002. Epub 2012 Aug 9.
• Background Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016 Oct 27;375(17):1660-1670. doi: 10.1056/NEJMra1600561. No abstract available.
• Background Zuberi BF, Alvi H, Zuberi FF, Rasheed T, Nawaz Z, Fatima-Tuz-Zohra. Frequency of minimal hepatic encepalopathy in illeterate patients with compensated cirrhosis. Pak J Med Sci. 2016 May-Jun;32(3):595-8. doi: 10.12669/pjms.323.9655.
• Background Gerber T, Schomerus H. Hepatic encephalopathy in liver cirrhosis: pathogenesis, diagnosis and management. Drugs. 2000 Dec;60(6):1353-70. doi: 10.2165/00003495-200060060-00008.
• Background Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016 May 6;2016(5):CD003044. doi: 10.1002/14651858.CD003044.pub4.
• Background Williams R, Bass N. Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8.
• Background Kimer N, Krag A, Moller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014 Jul;40(2):123-32. doi: 10.1111/apt.12803. Epub 2014 May 21.
• Background Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014 Nov;174(11):1727-33. doi: 10.1001/jamainternmed.2014.4746.
• Background Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Alexeeva O, Zupanets IA, Grinevich V, Baranovsky A, Dudar L, Fadieienko G, Kharchenko N, Klaryts'ka I, Morozov V, Grewal P, McCashland T, Reddy KG, Reddy KR, Syplyviy V, Bass NM, Dickinson K, Norris C, Coakley D, Mokhtarani M, Scharschmidt BF; HALT-HE Study Group. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology. 2014 Mar;59(3):1073-83. doi: 10.1002/hep.26611.
• Background American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available.
• Background Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016 Apr 18;4:CD003044. doi: 10.1002/14651858.CD003044.pub3.
• Background Shehata HH, Elfert AA, Abdin AA, Soliman SM, Elkhouly RA, Hawash NI, Soliman HH. Randomized controlled trial of polyethylene glycol versus lactulose for the treatment of overt hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2018 Dec;30(12):1476-1481. doi: 10.1097/MEG.0000000000001267.
• Background Naderian M, Akbari H, Saeedi M, Sohrabpour AA. Polyethylene Glycol and Lactulose versus Lactulose Alone in the Treatment of Hepatic Encephalopathy in Patients with Cirrhosis: A Non-Inferiority Randomized Controlled Trial. Middle East J Dig Dis. 2017 Jan;9(1):12-19. doi: 10.15171/mejdd.2016.46.
• Background Friedman S, Schiano T. Cirrhosis and its sequelae. Cecil Textbook of Medicine 22nd ed Philadelphia, Pa: Saunders. 2004:936-44.
• Background American College of R. Expert Panel on Gastrointestinal Imaging. Liver lesion characterization Reston, Va: American College of Radiology. 2002.
• Background Hassanein TI, Hilsabeck RC, Perry W. Introduction to the Hepatic Encephalopathy Scoring Algorithm (HESA). Dig Dis Sci. 2008 Feb;53(2):529-38. doi: 10.1007/s10620-007-9895-0. Epub 2007 Aug 21.
• Background Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012 Mar;55(3):965-7. doi: 10.1002/hep.25551. No abstract available.
• Background Mendez-Sanchez N, Aguilar-Ramirez JR, Reyes A, Dehesa M, Juorez A, Castneda B, Sanchez-Avila F, Poo JL, Guevara Gonzalez L, Lizardi J, Valdovinos MA, Uribe M, Contreras AM, Tirado P, Aguirre J, Rivera-Benitez C, Santiago-Santiago R, Bosques-Padilla F, Munoz L, Guerroro A, Ramos M, Rodriguez-Hernandez H, Jacobo-Karam J; Grupo de Estudio, Asociacion Mexicana de Hepatologia. Etiology of liver cirrhosis in Mexico. Ann Hepatol. 2004 Jan-Mar;3(1):30-3.

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Indications