Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE)

Official title

Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE): an Invesitgator-initiated, Open-label, Multicenter, Randomized Controlled Trial

Overview

Hepatic encephalopathy (HE), a severe complication of decompensated cirrhosis, is characterized as neurocognitive dysfunction. Emerging evidence suggests the potential role of human albumin infusion for the treatment of HE, but its optimal dosage remains undefined. Therefore, the investigators planned a randomized controlled trial (RCT) to compare the efficacy of human albumin infusion at different dosages in in patients with liver cirrhosis and overt HE.

Detailed description

Overall, 174 patients with a diagnosis of liver cirrhosis, overt HE, and a serum albumin level of 23-30g/L will be enrolled. They will be stratified according to the severity of overt HE and randomly assigned at a ratio of 1:1 into the groups of human albumin infusion at a modified dosage and a routine dosage. The primary endpoint is the improvement of overt HE within 3-5 days after treatment. The secondary endpoints include recurrence of overt HE, survival, and adverse events.

Interventions

• Drug Human albumin infusion at a modified dosage
  Participants receive intravenous infusion of human albumin at different dosages according to the serum albumin level.
• Drug Human albumin infusion at a routine dosage
  Participants receive intravenous infusion of human albumin according to the current clinical practice.
• Drug Lactulose
  All participants will receive standard treatment of overt HE according to the current practice guideline.
• Drug Rifaximin
  All participants will receive standard treatment of overt HE according to the current practice guideline.
• Drug Ornithine Aspartate
  All participants will receive standard treatment of overt HE according to the current practice guideline.
• Drug Branched-Chain Amino Acids
  All participants will receive standard treatment of overt HE according to the current practice guideline.
• Drug Arginine
  All participants will receive standard treatment of overt HE according to the current practice guideline.

Primary outcome measures

• Change of overt HE. [Time frame: 3-5 days]

Secondary outcome measures (4)

• Reversal of overt HE. [Time frame: 3-5 days]
• Recurrence of overt HE. [Time frame: 3 months]
• Adverse events [Time frame: 3 months]
• Survival [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• A definite diagnosis of liver cirrhosis and overt HE
• A serum albumin level of 23-30g/L
• Age ≥18 years old
• Sign the informed consent

Exclusion criteria

• Contraindications to human albumin infusion
• A history of transjugular intrahepatic portosystemic shunt
• A diagnosis of acute liver failure
• Severe heart and/or lung diseases
• Psychiatric or nervous diseases
• Pregnant or lactating

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Gastroenterology, General Hospital of Northern Theater Command (formerly cal — Shenyang

Publications

• Bai Z, Mendez-Sanchez N, Romeiro FG, Mancuso A, Philips CA, Tacke F, Basaranoglu M, Primignani M, Ibrahim M, Wong YJ, Nery FG, Teschke R, Ferreira CN, Munoz AE, Pinyopornpanish K, Thevenot T, Singh SP, Mohanty A, Satapathy SK, Ridola L, Maruyama H, Cholongitas E, Levi Sandri GB, Yang L, Shalimar, Yang Y, Villa E, Krag A, Wong F, Jalan R, O'Brien A, Bernardi M, Qi X; Liver Cirrhosis-related Complic PMID 37456673
• Sharma BC, Singh J, Srivastava S, Sangam A, Mantri AK, Trehanpati N, Sarin SK. Randomized controlled trial comparing lactulose plus albumin versus lactulose alone for treatment of hepatic encephalopathy. J Gastroenterol Hepatol. 2017 Jun;32(6):1234-1239. doi: 10.1111/jgh.13666. PMID 27885712
• Simon-Talero M, Garcia-Martinez R, Torrens M, Augustin S, Gomez S, Pereira G, Guevara M, Gines P, Soriano G, Roman E, Sanchez-Delgado J, Ferrer R, Nieto JC, Sunye P, Fuentes I, Esteban R, Cordoba J. Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: a randomized double-blind study. J Hepatol. 2013 Dec;59(6):1184-92. doi: 10.1016/j.jhep.2013.07.020. Epub PMID 23872605
• China L, Freemantle N, Forrest E, Kallis Y, Ryder SD, Wright G, Portal AJ, Becares Salles N, Gilroy DW, O'Brien A; ATTIRE Trial Investigators. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. N Engl J Med. 2021 Mar 4;384(9):808-817. doi: 10.1056/NEJMoa2022166. PMID 33657293
• Bai Z, Bernardi M, Yoshida EM, Li H, Guo X, Mendez-Sanchez N, Li Y, Wang R, Deng J, Qi X. Albumin infusion may decrease the incidence and severity of overt hepatic encephalopathy in liver cirrhosis. Aging (Albany NY). 2019 Oct 8;11(19):8502-8525. doi: 10.18632/aging.102335. Epub 2019 Oct 8. PMID 31596729
• Li Q, Tong H, Liu X, Liao F, Ma H, Zhou Z, Liu F, Shi H, Wang Z, Sun Y, Yao Q, Feng Y, Li X, Feng J, He Z, Peng Y, Bai Z, Zhu R, Cheng D, Xu C, He S, Yu H, Xie C, Yuan J, Wang X, Yang H, Zou Y, Li S, Li T, Hu S, Chen C, Chen Z, Lantinga MA, Bernardi M, Qi X, Tang C; On the behalf of Young Member Group of Chinese Gastroenterology Society. Human Albumin infusion in liver Cirrhosis and overt Hepatic PMID 41198206

Identifiers

NCT: NCT06483737 · XHNKKY-OHE-RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗