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Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis (RPPCLC)

Primary Purpose

Decompensated Cirrhosis

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Low-dose of Rifaximin
Conventional dose of Rifaximin
Sponsored by
Xin Zeng
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Decompensated Cirrhosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shanghai East HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

control group

the low-dose rifaximin treatment group

the conventional dose rifaximin treatment group

Arm Description

Group A: Patients in the control group were administered only conventional therapy

Group B

Group C

Outcomes

Primary Outcome Measures

The proportion of patients with progression of liver cirrhosis
The proportion of patients with progression of liver cirrhosis, which is defined as at least one additional stage of liver cirrhosis staging during the 24-week treatment phase

Secondary Outcome Measures

Incidence of overall complications resulting from decompensated liver cirrhosis
The incidence of overall complications resulting from decompensated liver cirrhosis in 12weeks and 24weeks, including refractory ascites, SBP, esophageal and gastric variceal bleeding (EGVB), overt hepatic encephalopathy(OHE), cute renal injury (AKI)/hepatorenal syndrome (HRS), primary hepatic carcinoma (PHC), etc.
Incidence of various complications of liver cirrhosis, including: refractory ascites, SBP, EGVB, OHE, AKI/HRS, PHC, etc.
The incidence of each complication resulting from decompensated liver cirrhosis in 12weeks and 24weeks, including refractory ascites, SBP, EGVB, OHE, AKI/HRS, PHC, etc.
The proportion of patients with progression of liver cirrhosis
The proportion of patients with progression of liver cirrhosis, which is defined as at least one additional stage of liver cirrhosis staging during the 12-week treatment phase
The proportion of patients with acute decompensated (AD)
The proportion of patients with acute decompensated (AD)
The proportion of patients with stable decompensated cirrhosis
The proportion of patients with stable decompensated cirrhosis, which is defined as patients with decompensated cirrhosis who, while receiving sustained prophylaxis with diuretics, and/or lactulose or rifaximin, and/or non-selective beta-blockers or repeated endoscopic treatment of esophagogastric varices, do not present episodes of AD for a long-time period.
The proportion of patients with recompensation of cirrhosis
The proportion of patients with recompensation of cirrhosis, which is defined as the clinical phase of the disease prior to the resolution of cirrhosis induced by successful treatment of the underlying aetiology.
All-cause mortality
All-cause mortality during the 24-week treatment phase
Complication-free survival time
Complication-free survival time during the treatment phase
Liver transplantation free survival time
Liver transplantation free survival time during the treatment phase
Child-Pugh score
Liver function reflected by Child-Pugh score. A higher Child-Pugh score mean a worse outcome
The proportion of patients with different Child-Pugh class
The proportion of patients with Child-Pugh A/B/C (Child-Pugh A: Child-Pugh score<7; Child-Pugh B: Child-Pugh score 7~9; Child-Pugh C: Child-Pugh score>9 )
Model for end-stage liver disease (MELD) score
Liver function reflected by MELD score. A higher MELD score mean a worse outcome

Full Information

First Posted
December 28, 2022
Last Updated
August 5, 2023
Sponsor
Xin Zeng
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1. Study Identification

Unique Protocol Identification Number
NCT05863364
Brief Title
Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis
Acronym
RPPCLC
Official Title
Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis: a Multi-center Randomized Prospective Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 18, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Xin Zeng

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Decompensated Cirrhosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
control group
Arm Type
No Intervention
Arm Description
Group A: Patients in the control group were administered only conventional therapy
Arm Title
the low-dose rifaximin treatment group
Arm Type
Experimental
Arm Description
Group B
Arm Title
the conventional dose rifaximin treatment group
Arm Type
Experimental
Arm Description
Group C
Intervention Type
Drug
Intervention Name(s)
Low-dose of Rifaximin
Other Intervention Name(s)
Low-dose of Xifaxan
Intervention Description
The patients in group B were given rifaximin with the dose of 600mg/d (600mg, qd) for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Conventional dose of Rifaximin
Other Intervention Name(s)
Conventional dose of Xifaxan
Intervention Description
the patients in group C were delivered 1200mg/d (600mg, bid) for 24 weeks
Primary Outcome Measure Information:
Title
The proportion of patients with progression of liver cirrhosis
Description
The proportion of patients with progression of liver cirrhosis, which is defined as at least one additional stage of liver cirrhosis staging during the 24-week treatment phase
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Incidence of overall complications resulting from decompensated liver cirrhosis
Description
The incidence of overall complications resulting from decompensated liver cirrhosis in 12weeks and 24weeks, including refractory ascites, SBP, esophageal and gastric variceal bleeding (EGVB), overt hepatic encephalopathy(OHE), cute renal injury (AKI)/hepatorenal syndrome (HRS), primary hepatic carcinoma (PHC), etc.
Time Frame
12 and 24weeks
Title
Incidence of various complications of liver cirrhosis, including: refractory ascites, SBP, EGVB, OHE, AKI/HRS, PHC, etc.
Description
The incidence of each complication resulting from decompensated liver cirrhosis in 12weeks and 24weeks, including refractory ascites, SBP, EGVB, OHE, AKI/HRS, PHC, etc.
Time Frame
12 weeks and 24 weeks
Title
The proportion of patients with progression of liver cirrhosis
Description
The proportion of patients with progression of liver cirrhosis, which is defined as at least one additional stage of liver cirrhosis staging during the 12-week treatment phase
Time Frame
12 weeks
Title
The proportion of patients with acute decompensated (AD)
Description
The proportion of patients with acute decompensated (AD)
Time Frame
12 and 24 weeks
Title
The proportion of patients with stable decompensated cirrhosis
Description
The proportion of patients with stable decompensated cirrhosis, which is defined as patients with decompensated cirrhosis who, while receiving sustained prophylaxis with diuretics, and/or lactulose or rifaximin, and/or non-selective beta-blockers or repeated endoscopic treatment of esophagogastric varices, do not present episodes of AD for a long-time period.
Time Frame
24 weeks
Title
The proportion of patients with recompensation of cirrhosis
Description
The proportion of patients with recompensation of cirrhosis, which is defined as the clinical phase of the disease prior to the resolution of cirrhosis induced by successful treatment of the underlying aetiology.
Time Frame
24 weeks
Title
All-cause mortality
Description
All-cause mortality during the 24-week treatment phase
Time Frame
24 weeks
Title
Complication-free survival time
Description
Complication-free survival time during the treatment phase
Time Frame
24 weeks
Title
Liver transplantation free survival time
Description
Liver transplantation free survival time during the treatment phase
Time Frame
24 weeks
Title
Child-Pugh score
Description
Liver function reflected by Child-Pugh score. A higher Child-Pugh score mean a worse outcome
Time Frame
24 weeks
Title
The proportion of patients with different Child-Pugh class
Description
The proportion of patients with Child-Pugh A/B/C (Child-Pugh A: Child-Pugh score<7; Child-Pugh B: Child-Pugh score 7~9; Child-Pugh C: Child-Pugh score>9 )
Time Frame
24 weeks
Title
Model for end-stage liver disease (MELD) score
Description
Liver function reflected by MELD score. A higher MELD score mean a worse outcome
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Incidence of ACLF
Description
The proportion of patients with ACLF during the treatment phase
Time Frame
24 weeks
Title
Health-related quality of life (HRQoL)
Description
HRQoL evaluated with chronic liver disease questionnaire,CLDQ)
Time Frame
24 weeks
Title
Sarcopenia
Description
Sarcopenia evaluated with L3 skeletal muscle index (L3-SMI) based on CT or MRI
Time Frame
24 weeks
Title
Myosteatosis
Description
Myosteatosis evaluated with L3 skeletal muscle density (L3-SMD) based on CT or MRI
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xin Zeng, Dr.
Phone
086018918353309
Email
zengxinmd1978@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xin Zeng, Dr.
Organizational Affiliation
Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai East Hospital
City
Shanghai
ZIP/Postal Code
200120
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Na Li, Dr.
Phone
086018661803012
Email
zengxinmd1978@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Rifaximin for Preventing Progression and Complications in Patients With Decompensated Liver Cirrhosis

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