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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: Rifaximin; Drug: Ciprofloxacin

Detailed Description

• 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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Decompensated cirrhotic patients with

   • serum bilirubin > 3.2 mg/dL
   • prothrombin time < 25%
   • serum creatinine > 3 mg/dL
2. Active gastrointestinal bleeding
3. Hepatic encephalopathy > grade 2
4. Patients who have clinical, biochemical or radiological data suggesting hepatocellular carcinoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin group; Rifaximin 1200 mg/day orally for 6 months	Drug: Rifaximin; rifaximin 1200 mg/day orally for 6 months; Other Names: Normix
Active Comparator: Control group; Ciprofloxacin 500 mg/day orally for 6 months	Drug: Ciprofloxacin; ciprofloxacin 500 mg/day orally for 6 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Jeong-Hoon Lee, M.D., Ph.D., Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (Estimate): December 13, 2013

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: recurrence; spontaneous bacterial peritonitis; liver cirrhosis; ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Peritoneal Diseases; Disease Attributes; Intraabdominal Infections; Recurrence; Peritonitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Rifaximin; Ciprofloxacin
• Other Study ID Numbers: Rifaximin_SBP