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

Cirrhosis Clinical Trial

— ProPILARifax  

Official title:

A Multicenter, Double-blind, Placebo-controlled Randomized Clinical Trial Comparing Two Strategies of Primary Prophylaxis of Spontaneous Bacterial Peritonitis in Severe Cirrhotic Patients With Ascites : Using or Not Using Rifaximin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03069131
• Other study ID #: ProPILA-Rifax
• Status: Completed
• Phase: Phase 3
• Start date: March 20, 2018
• Est. completion date: March 20, 2023

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: March 20, 2023
• Est. primary completion date: June 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Cirrhosis
• Peritonitis

Intervention

Drug:
• Rifaximin
twice daily administration of 1 tablet containing 550 mg of active rifaximin

Other:
• Placebo
twice daily administration of 1 rifaximin placebo tablet

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU d'Angers	Angers
France	CHU de Besançon	Besançon
France	Hôpital Jean Verdier	Bondy
France	CHU Caen	Caen
France	Hôpital Beaujon	Clichy
France	CHIC de Créteil	Créteil
France	CHU Grenoble	La Tronche
France	CHRU de Lille	Lille
France	Hopital de la croix-rousse	Lyon
France	CHU Montpellier	Montpellier
France	CHU de Nice	Nice
France	Hôpital Pitié Salpêtrière	Paris
France	CHU de Reims	Reims
France	CHU de Rennes	Rennes
France	CHU Rouen	Rouen
France	CHU de Toulouse	Toulouse
France	CHU Tours	Tours

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon	Alfasigma S.p.A., LC2 PHARMA

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	death	record of death whatever the cause	12 months
Secondary	Hospital mortality rate and mortality rate at 3 months	survival during hospitalization and at 3 months	3 months
Secondary	Hospital mortality rate and mortality rate at 6 months	survival during hospitalization and at 6 months	6 months
Secondary	Incidence of spontaneous bacterial peritonitis during follow-up	Bacterial analysis of ascites	12 months
Secondary	Incidence of the other complications of liver cirrhosis during follow-up	complications of liver cirrhosis : HE, gastrointestinal bleeding and hepatorenal syndrome	12 months
Secondary	Patient hospitalizations during follow-up	number of days of hospitalization during 12 months of follow-up	12 months
Secondary	Quantitative variations of IL-6 in serum between day 1 and day 30	Dosage of IL-6 in serum at D1 and D30	1 month
Secondary	Quantitative variations of lipopolysaccharides (LPS) in serum between day 1 and day 30	Dosage of LPS in serum at D1 and D30	1 month
Secondary	Quantitative variations of copeptin in serum between day 1 and day 30	Dosage of copeptin in serum at D1 and D30	1 month
Secondary	Quantitative variations of CRP in serum between day 1 and day 30	Dosage of CRP in serum at D1 and D30	1 month
Secondary	Quantitative variations of von Willebrand Factor antigen in serum between day 1 and day 30	Dosage of von Willebrand Factor antigen in serum at D1 and D30	1 month
Secondary	Composition of the intestinal microbiota	analyzis of microbiota (quantity and quality of main bacterial strains) in 25 patients from arms A and B at day 1, and at months 3, 6, 12 and 18	up to 18 months
Secondary	Safety analysis of the study drug	Record of adverse events and serious adverse events in each arm	12 months