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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Overt Hepatic Encephalopathy
• Intervention / Treatment: Drug: Human albumin infusion at a modified dosage; Drug: Human albumin infusion at a routine dosage; Drug: Lactulose; Drug: Rifaximin; Drug: Ornithine Aspartate; Drug: Branched-Chain Amino Acids; Drug: Arginine

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.

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xingshun Qi; Phone Number: 18909881019; Email: xingshunqi@126.com
• Study Contact Backup: Name: Qianqian Li; Phone Number: 13940307473; Email: 1208594776@qq.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)
      • Contact: Xingshun Qi; Phone Number: 18909881019; Email: xingshunqi@126.com
      • Contact: Qianqian Li; Phone Number: 13940307473; Email: 1208594776@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Routine dosage group; Intravenous infusion of human albumin 10-20g.	Drug: Human albumin infusion at a routine dosage; Participants receive intravenous infusion of human albumin according to the current clinical practice.; Other Names: AlbuRx; Drug: Lactulose; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Duphalac; Drug: Rifaximin; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Xifaxan; Drug: Ornithine Aspartate; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Hepa-Merz; Drug: Branched-Chain Amino Acids; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Compound amino acid injection; Drug: Arginine; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Arginine Hydrochloride Injection
Experimental: Modified dosage group; Intravenous infusion of human albumin 30-60g.	Drug: Human albumin infusion at a modified dosage; Participants receive intravenous infusion of human albumin at different dosages according to the serum albumin level.; Other Names: AlbuRx; Drug: Lactulose; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Duphalac; Drug: Rifaximin; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Xifaxan; Drug: Ornithine Aspartate; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Hepa-Merz; Drug: Branched-Chain Amino Acids; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Compound amino acid injection; Drug: Arginine; All participants will receive standard treatment of overt HE according to the current practice guideline.; Other Names: Arginine Hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of overt HE.	The change of HE is defined as a decrease or an increase of at least one grade of the West Haven criteria after treatment.	3-5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversal of overt HE.	The reversal of HE is defined as clinical symptoms of overt HE disappear after treatment.	3-5 days
Recurrence of overt HE.	Clinical symptoms related to overt HE recur and can be diagnosed with overt HE again according to the West Haven criteria.	3 months
Adverse events	Adverse events will be monitored, including allergy, heart failure, pulmonary edema, acute hemolysis, renal dysfunction, and neuropsychiatric abnormalities.	3 months
Survival	All participants will be followed by telephone to record survival status, including the major cause and date of death.	3 months

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Investigators: Principal Investigator: Xingshun Qi, Department of Gastroenterology, General Hospital of Northern Theater Command

Publications and helpful links

General 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 Complications (LCC)-International Special Interest Group. Use of albumin infusion for cirrhosis-related complications: An international position statement. JHEP Rep. 2023 May 5;5(8):100785. doi: 10.1016/j.jhepr.2023.100785. eCollection 2023 Aug.
• 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.
• 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 2013 Jul 19.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: survival; inflammation; hepatic encephalopathy; oxidative stress; human albumin; liver cirrhosis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Fibrosis; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Inflammation; Liver Cirrhosis; Hepatic Encephalopathy; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Polycyclic Compounds; Amino Acids; Polysaccharides; Heterocyclic Compounds, 4 or More Rings; Disaccharides; Oligosaccharides; Sugars; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Amino Acids, Basic; Amino Acids, Diamino; Amino Acids, Essential; Rifaximin; Lactulose; Albumins; ornithylaspartate; Amino Acids, Branched-Chain; Arginine
• Other Study ID Numbers: XHNKKY-OHE-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No