Rifaximin for the Secondary Prevention of Spontaneous Bacterial Peritonitis Recurrence in Cirrhotic Patients

Study Overview
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Brief Summary
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The aim of this study is to evaluate whether long-term rifaximin administration reduces spontaneous bacterial peritonitis recurrence rate in cirrhotic patients.

Detailed Description
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Rifaximin is an antibiotic with a broad-spectrum activity against gram-positive and gram-negative microorganisms, both aerobes and anaerobes within the gastrointestinal tract. The main advantage of rifaximin is that it is poorly absorbable, which minimizes the antimicrobial resistance and adverse events and renders the drug safe in all patient populations. In addition, rifaximin has a better activity against gram-positive organisms than norfloxacin. The appreciation of the potential role of enteric flora in the pathogenesis of several gastrointestinal diseases has broadened the clinical use of rifaximin, which is now used for hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease, and Clostridium difficile infection. Theoretically, by reducing the total number of the gut bacteria, rifaximin could also be used to achieve intestinal decontamination in patients with liver cirrhosis and ascites, thus preventing spontaneous bacterial peritonitis. A small retrospective study concluded that rifaximin suppresses intestinal bacterial overgrowth, bacterial translocation in cirrhotic patients with ascites with no history of previous spontaneous bacterial peritonitis episodes. Prospective clinical trials are warranted to evaluate the role of rifaximin for prevention of spontaneous bacterial peritonitis recurrence in cirrhotic patients.

Official Title
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Rifaximin for the Secondary Prevention of Spontaneous Bacterial Peritonitis Recurrence in Cirrhotic Patients: A Prospective, Multicenter, Randomized, Open-label, Controlled Phase III Study

Conditions
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Spontaneous Bacterial Peritonitis

Intervention / Treatment
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* Drug: Rifaximin
* Drug: Ciprofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with cirrhosis based on clinical, biochemical, ultrasonographic and/or histological criteria Patients who had recovered from an episode of spontaneous bacterial peritonitis Age > 18 and <80 years Exclusion Criteria: Decompensated cirrhotic patients with serum bilirubin > 3.2 mg/dL prothrombin time < 25% serum creatinine > 3 mg/dL Active gastrointestinal bleeding Hepatic encephalopathy > grade 2 Patients who have clinical, biochemical or radiological data suggesting hepatocellular carcinoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Rifaximin group<br>Rifaximin 1200 mg/day orally for 6 months | Drug: Rifaximin<br>* rifaximin 1200 mg/day orally for 6 months<br>* Other names: Normix;|
| Active Comparator: Control group<br>Ciprofloxacin 500 mg/day orally for 6 months | Drug: Ciprofloxacin<br>* ciprofloxacin 500 mg/day orally for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The recurrence rate of spontaneous bacterial peritonitis | The proportion of patients who recurred spontaneous bacterial peritonitis. | every 4 weeks, up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | All-cause mortality and cause-specific mortality (mortality due to spontaneous bacterial peritonitis) | up to 24 weeks | 
| The recurrence of culture-negative spontaneous bacterial peritonitis | The proportion of patients who recurred culture-negative spontaneous bacterial peritonitis. | every 4 weeks, up to 24 weeks | 
| Causative bacteria of recurrent spontaneous bacterial peritonitis | Causative bacteria of recurrent spontaneous bacterial peritonitis and susceptibility | every 4 weeks, up to 24 weeks | 
| Change of gut microbiota | Gut microbiota will be analyzed at baseline and week 12 | at baseline, week 12 | 
| Infections other than spontaneous bacterial peritonitis | Infections other than spontaneous bacterial peritonitis (i.e. urinary tract infection, respiratory tract infection, etc.) | every 4 weeks, up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cirrhosis, ascites, spontaneous bacterial peritonitis, recurrence