Clinical trial NCT05863364: Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis
Official title: Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis: a Multi-center Randomized Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Decompensated Cirrhosis
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2023-05-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: It is still not clear whether rifaximin can prevent the progression of liver cirrhosis, reduce the overall complications and improve the survival in patients with decompensated cirrhosis. This is a multi-center open-labelled randomized prospective study to evaluate the efficacy and safety of rifaximin in preventing the progression and complications in cirrhotic patients, and explore its reasonable dosage and possible mechanism. A total of 150 patients with decompensated liver cirrhosis will be enrolled in the study and randomly divided into three groups (the control group (A), the low-dose rifaximin treatment group (B), and conventional dose rifaximin treatment group (C)) with a ratio of 1:2:2. The patients in group B are given rifaximin with the dose of 600mg/d (600mg, qd) for 24 weeks, and the patients in group C are delivered 1200mg/d (600mg, bid) of rifaximin .During the entire study period, all other therapeutic strategies are kept unchanged in all the groups as long as possible. The proportion of patients with progression of cirrhosis, the incidence of total complications and each complication, survival rate and time, liver function and adverse events will be compared among the three groups. This study might provide a new feasible method with clinical application prospects for preventing the progression and reducing the incidence of liver cirrhosis related complications, improve the prognosis of patients with decompensated liver cirrhosis, and save medical resources.

Detailed description: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP), the two major complications of liver cirrhosis. However, it is still not clear whether rifaximin can prevent the progression of liver cirrhosis, reduce the overall complications and improve the survival in patients with decompensated cirrhosis. Additionally, the role of rifaximin in the treatment of liver cirrhosis has not been fully clarified. We designed a multi-center open-labelled randomized prospective study to evaluate the efficacy and safety of rifaximin in preventing the progression and complications in cirrhotic patients, and explore its reasonable dosage and possible mechanism. A total of 150 patients with decompensated liver cirrhosis will be enrolled in the study. They will be randomly divided into three groups (the control group (A), the low-dose rifaximin treatment group (B), and conventional dose rifaximin treatment group (C)) with a ratio of 1:2:2. The patients in group B are given rifaximin with the dose of 600mg/d (600mg, qd) for 24 weeks, and the patients in group C are delivered 1200mg/d (600mg, bid) of rifaximin .During the entire study period, all other therapeutic strategies, such as antiviral agents, non-selective beta-blockers, liver protectants, and diuretics, are kept unchanged in all the groups as long as possible. The proportion of patients with progression of cirrhosis, acute decompensation, acute-on-chronic liver failure (ACLF), decompensation and stable decompensated cirrhosis, the incidence of total complications and each complication, survival rate and time, liver function and adverse events will be compared among the three groups. This study might provide a new feasible method with clinical application prospects for preventing the progression and reducing the incidence of liver cirrhosis related complications, improve the prognosis of patients with decompensated liver cirrhosis, and save medical resources.

Eligibility criteria: Inclusion Criteria:

* With a clinical diagnosis of decompensated liver cirrhosis on the basis of typical clinical manifestations, laboratory tests, imaging appearances and/or representative pathology results of liver biopsy. Decompensation of the disease was defined by at least having an episode of severe complications, including ascites, SBP, EGVB and HE.

Exclusion Criteria:

* Episodes of overt HE, EGVB or SBP within 4 weeks before the screening visit
* Uncontrolled severe infection or antibiotic use within 2 weeks before the screening visit
* Hepatitis B virus (HBV) DNA ≥ 500 copy/mL，or receipt of standard antiviral treatment for hepatitis B for less than 12 months
* Receiving antiviral treatment for hepatitis C or receipt of antiviral treatment for hepatitis C within 12 months before the screening visit
* If patients with autoimmune liver disease have been treated with ursodeoxycholic acid, hormone or other immunosuppressants, the dose stability time is less than 6 months
* With history of alcoholism in the last 12 weeks or unwilling to stop alcohol abuse after inclusion (≥ 20 g/day for women or ≥ 30 g/day for men)
* With confirmed or suspected malignancies
* Severe jaundice (serum total bilirubin level ≥ 85 μmol/L)
* Obvious renal dysfunction (serum creatinine ≥ 1.2-fold of upper normal limits)
* Severe electrolyte abnormality (serum sodium level \< 125 mmol/L )
* Life-threatening leucocytopenia (white blood cell count \< 1 × 10\^9/L )
* Poorly controlled hypertension, diabetes mellitus or other severe heart and respiratory diseases (NYHA Ⅲ/Ⅳ, COPD GOLD C)
* With drug abuse, methadone treatment, drug dependence or mental illness
* HIV seropositivity
* Known to be allergic to rifaximin
* Pregnant and lactating women or women who do not rule out pregnancy
* Those who have participated in other drug trials within 12 weeks

Primary outcomes:
measure: The proportion of patients with progression of liver cirrhosis
timeFrame: 24 weeks
Secondary outcomes:
measure: Incidence of overall complications resulting from decompensated liver cirrhosis
timeFrame: 12 and 24weeks
measure: Incidence of various complications of liver cirrhosis, including: refractory ascites, SBP, EGVB, OHE, AKI/HRS, PHC, etc.
timeFrame: 12 weeks and 24 weeks
measure: The proportion of patients with progression of liver cirrhosis
timeFrame: 12 weeks
measure: The proportion of patients with acute decompensated (AD)
timeFrame: 12 and 24 weeks
measure: The proportion of patients with stable decompensated cirrhosis
timeFrame: 24 weeks
measure: The proportion of patients with recompensation of cirrhosis
timeFrame: 24 weeks
measure: All-cause mortality
timeFrame: 24 weeks
measure: Complication-free survival time
timeFrame: 24 weeks
measure: Liver transplantation free survival time
timeFrame: 24 weeks
measure: Child-Pugh score
timeFrame: 24 weeks
measure: The proportion of patients with different Child-Pugh class
timeFrame: 24 weeks
measure: Model for end-stage liver disease (MELD) score
timeFrame: 24 weeks
Other outcomes:
measure: Incidence of ACLF
timeFrame: 24 weeks
measure: Health-related quality of life (HRQoL)
timeFrame: 24 weeks
measure: Sarcopenia
timeFrame: 24 weeks
measure: Myosteatosis
timeFrame: 24 weeks
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
Study officials:
affiliation: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine
name: Xin Zeng, Dr.
role: PRINCIPAL_INVESTIGATOR
References: