Rifaximin Predicts the Complications of Decompensated Cirrhosis

Naval Military Medical University (Second Military Medical University)

Status and phase: Unknown; Phase 4

Conditions: Cirrhosis

Treatments: Drug: rifaximin

Study type: Interventional

Funder types: Other

Identifiers

NCT02074280

LPDLCC-1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 3 patient groups

high dose of rifaximin

Experimental group

Description:

rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment

Treatment:

Drug: rifaximin

low dose of rifaximin

Experimental group

Description:

rifaximin 400 mg bid,orally, 2 weeks

Treatment:

Drug: rifaximin

control

No Intervention group

Description:

conventional treatment