Rifaximin Predicts the Complications of Decompensated Cirrhosis

Phase 4

• Conditions: Cirrhosis
• Interventions: Drug: rifaximin

• Registration Number: NCT02074280
• Lead Sponsor: Shanghai Changzheng Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-10
• Status Verified: 2014-02
• Study First Submitted: 2014-02-15
• Study First Submitted QC: 2014-02-26
• Last Update Submitted: 2014-02-26
• Study First Posted: 2014-02-28
• Last Update Posted: 2014-02-28
• Primary Completion: 2014-06
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
high dose of rifaximin	rifaximin	rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment
low dose of rifaximin	rifaximin	rifaximin 400 mg bid,orally, 2 weeks

Primary Outcome Measures

Name	Time	Method
Serum endotoxin level	4 weeks
Hydrogen breath test	4 weeks
Fecal flora	4 weeks

Secondary Outcome Measures

Name	Time	Method
Serum levels of inflammatory factors	4 weeks
Liver biochemistry tests	4 weeks
Numbers of complications of cirrhosis	4 weeks

Trial Locations

Locations (1)

Shanghai changzheng Hospital; 🇨🇳 Shanghai, Shanghai, China