Two Strategies of Primary Prophylaxis of Spontaneous Bacterial Peritonitis in Severe Cirrhotic Patients With Ascites (ProPILARifax)

Centre Hospitalier Universitaire de Besancon

Status and phase

Completed

Phase 3

Conditions

Peritonitis

Cirrhosis

Ascites

Treatments

Other: Placebo

Drug: Rifaximin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03069131

ProPILA-Rifax

Details and patient eligibility

About

We wish to perform a multicenter, double-blind RCT with two parallel-group stratified on the center, comparing rifaximin to no rifaximin (placebo) for the primary prophylaxis of SBP in 'severe' cirrhotic patients with large ascites. The primary outcome will be the 12-month survival.

Enrollment

160 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Cirrhosis diagnosed on clinical, radiological and/or histological findings
Patients with large ascites (i.e., grade 3 ascites requiring paracentesis). Patients with grade 2 ascites are also authorized.
Ascites with a low protein level in ascitic fluid (< 15 g/L) with one of the following three conditions:
1. impaired renal function defined by serum creatinine ≥ 106 mmol/L, uremia ≥ 9 mmol/L or serum sodium ≤ 130 mmol/L), or
2. severe liver impairment defined by Child-Pugh score ≥ 9 with serum total bilirubin levels ≥ 51 mmol/L.
3. severe liver impairment defined by Child-Pugh C
Patient who signed an informed consent form
Patient with a social security system
Woman must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the study if childbearing potential.
Patients who needs a TIPS if the procedure is performed 3 months or more following the randomization
Patients with severe alcoholic hepatitis can be considered for inclusion if the MELD score < 30 and the Maddrey Discriminant Function < 60 providing that the patient is not infected (and consequently, will not receive antibiotics) and has not yet received corticosteroid (if necessary). Patients not responding to corticosteroid at day 7 (according to the Lille score) could be include after a wash-out of steroids for a period of 7 days.

Exclusion criteria

Pregnant woman or breastfeeding
Vulnerable person regarding french law
Individual under legal protection measure
Individual unable to exprim his/her consent
Person under 18 years of age and over 80 years of age
Transplanted patients, HIV infection (or patients who deny HIV serology) or immunosuppressive therapy (including patients under corticosteroids for severe alcoholic hepatitis if the patients respond to steroids with improvement of liver function)
Patients with a liver transplant project and an estimated waiting time for liver transplantation of 3 months or less
Past SBP or any present bacterial infection
Patient who have received a TIPS procedure before rhe randomization
Patients with an alfapump
Patient receiving antibiotics (including rifaximin) in the 7 days preceding the inclusion in this study exept for patients participating to the microbiota study (15 days).
Hypersensitivity to rifaximin, derivatives of rifamycin or one of the constituents of the preparation
Hepatocellular carcinoma outside the Milan criteria, other cancer at a palliative stage
Any clinical situation with a very low short-terme prognosis (other than cirrhosis), i.e. a survival estimated lower than one month
Gastrointestinal bleeding within 7 days
Intestinal obstruction
Grade 3 hepatic encephalopathy (HE) during the previous 6 months before randomization
Chronic heart failure (stage III or IV of the New York Heart Association [NYHA] Functional Classification
Patient judged as noncompliant
Patients who cannot receive a clear information and who have no trusted relatives
Patient who refuses the participation agreement by signing the information form and consent as defined in the protocol.
Exclusion period from another biomedical study