Rifaximin Predicts the Complications of Decompensated Cirrhosis

Study Overview
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Brief Summary
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Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and increased intestinal permeability all leading to an increase in bacterial translocation and increased endotoxemia. Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics or bowel decontamination might improve long-term outcomes in patients with cirrhosis. The aim of this study was to explore the suitable dose of rifaximin to alleviate endotoxemia and prevent the complications of advanced cirrhosis.

Detailed Description
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Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and increased intestinal permeability all leading to an increase in bacterial translocation and increased endotoxemia. Cirrhotics with bacterial translocation and endotoxemia manifest hemodynamic derangement with lower systemic vascular resistance, higher cardiac output, and lower mean arterial pressure. Moreover, endotoxins may increase portal pressure by increasing vascular resistance which may be promoted through the cytokine-stimulated intrahepatic release of endothelin and cyclo-oxygenase products. Indeed, bacterial infections are common in cirrhotic patients and have approximately 30% mortality at one month and a further 30% mortality at 12 months as documented in a systematic review comprising almost 12 000 patients. It follows that altering gut flora to decrease endotoxin levels may lead to improved prognosis in cirrhosis. Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics or bowel decontamination might improve long-term outcomes in patients with cirrhosis, not only by reducing the risk of infections but also by reducing hepatic vein pressure gradient (HVPG). The aim of this study was to explore the suitable dose of rifaximin to alleviate endotoxemia and prevent the complications of advanced cirrhosis.

Official Title
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Rifaximin Predicts the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: rifaximin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Decompensated cirrhosis Child-Pugh B or C stage Exclusion Criteria: severe complications of cirrhosis in the past one month. renal dysfunction. administration of antibiotics in the past two weeks. malignant tumors. HIV infection. severe heart and lung disease sensitivity to rifaximin Pregnancy and lactation woman Patients who have took part in other clinical trials in the past three months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high dose of rifaximin<br>rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment | Drug: rifaximin<br>* Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.<br>|
| Experimental: low dose of rifaximin<br>rifaximin 400 mg bid,orally, 2 weeks | Drug: rifaximin<br>* Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.<br>|
| No Intervention: control<br>conventional treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum endotoxin level |  | 4 weeks | 
| Hydrogen breath test |  | 4 weeks | 
| Fecal flora |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver biochemistry tests |  | 4 weeks | 
| Numbers of complications of cirrhosis |  | 4 weeks | 
| Serum levels of inflammatory factors |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rifaximin, endotoxemia, cirrhosis, advanced cirrhosis