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

NCT03069131 | Completed Phase 3 DMC

• 1 other identifier: ProPILA-Rifax
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Cirrhosis; Ascites; Peritonitis

Keywords

primary prophylaxis; rifaximin

Outcome Measures

Primary Outcomes (1)

• death

  record of death whatever the cause

  12 months

Secondary Outcomes (12)

• Hospital mortality rate and mortality rate at 3 months

  3 months

• Hospital mortality rate and mortality rate at 6 months

  6 months

• Incidence of spontaneous bacterial peritonitis (SBP) during follow-up

  12 months

• Incidence of the other complications of liver cirrhosis during follow-up

  12 months

• Patient hospitalizations during follow-up

  12 months

Study Arms (2)

Active rifaximin

EXPERIMENTAL

Drug: Rifaximin

Rifaximin placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Rifaximin DRUG

twice daily administration of 1 tablet containing 550 mg of active rifaximin

Active rifaximin

Placebo OTHER

twice daily administration of 1 rifaximin placebo tablet

Rifaximin placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• impaired renal function defined by serum creatinine ≥ 106 mmol/L, uremia ≥ 9 mmol/L or serum sodium ≤ 130 mmol/L), or
• severe liver impairment defined by Child-Pugh score ≥ 9 with serum total bilirubin levels ≥ 51 mmol/L.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Alfasigma S.p.A.: collaborator
• LC2 PHARMA: collaborator

Study Sites (18)

CHU Amiens

Amiens, 80054, France

Location

CHU d'Angers

Angers, France

Location

CHU de Besançon

Besançon, France

Location

Hôpital Jean Verdier

Bondy, France

Location

CHU Caen

Caen, 14033, France

Location

Hôpital Beaujon

Clichy, France

Location

CHIC de Créteil

Créteil, France

Location

CHU Grenoble

La Tronche, 38700, France

Location

CHRU de Lille

Lille, France

Location

Hopital de la croix-rousse

Lyon, 69004, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU de Nice

Nice, France

Location

Hôpital Pitié Salpêtrière

Paris, France

Location

CHU de Reims

Reims, France

Location

CHU de Rennes

Rennes, France

Location

CHU Rouen

Rouen, 76031, France

Location

CHU de Toulouse

Toulouse, France

Location

CHU Tours

Tours, 37044, France

Location

Related Publications (1)

• Thevenot T, Elkrief L, Bureau C, Bardou-Jacquet E, Rosa I, Nguyen-Khac E, Oberti F, Pitta A, Mallet M, Lebosse F, Louvet A, Meunier L, Nahon P, Ollivier-Hourmand I, Anty R, Francoz C, Riachi G, Meunier A, Cervoni JP, Tio G, Muller A, Cure-Martin A, Ladeira R, Clairet AL, Hocquet D, Di Martino V, Weil D, Desmarets M. Effect of rifaximin in patients with severe cirrhosis and ascites: A randomized double-blind placebo-controlled trial. J Hepatol. 2025 Dec;83(6):1320-1327. doi: 10.1016/j.jhep.2025.06.019. Epub 2025 Jul 11.

  PMID: 40653111 DERIVED

MeSH Terms

Conditions

Fibrosis; Ascites; Peritonitis

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraabdominal Infections; Infections; Peritoneal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Rodolphe Anty, MD

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

• Edouard Bardou-Jacquet, MD

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

• Christophe Bureau, MD, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

• Vincent Di Martino, MD, PhD

  CHRU de Besançon

  PRINCIPAL INVESTIGATOR

• Claire Francoz, MD

  Hôpital Beaujon, Clichy

  PRINCIPAL INVESTIGATOR

• Alexandra Heurgue-Berlot, MD

  CHU de Reims

  PRINCIPAL INVESTIGATOR

• Marianne Latournerie, MD

  Centre Hospitalier Universitaire Dijon

  PRINCIPAL INVESTIGATOR

• Alexandre Louvet, MD, PhD

  CHRU de Lille

  PRINCIPAL INVESTIGATOR

• Pierre Nahon, MD, PhD

  Hôpital Jean Verdier, Bondy

  PRINCIPAL INVESTIGATOR

• Frédéric Oberti, MD

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

• Isabelle Rosa-Hezode, MD

  CHIC de Créteil

  PRINCIPAL INVESTIGATOR

• Marika Rudler, MD

  Hôpital Pitié-Salpêtrière, APHP

  PRINCIPAL INVESTIGATOR

• Matthieu Schnee, MD

  Hôpital La Roche-sur-Yon

  PRINCIPAL INVESTIGATOR

• Ghassan Riachi, MD

  CHU Rouen

  PRINCIPAL INVESTIGATOR

• Isabelle Ollivier, MD

  CHU CAEN

  PRINCIPAL INVESTIGATOR

• Eric Nguyen-Khac, MD, PhD

  CHU Amiens

  PRINCIPAL INVESTIGATOR

• Laure Elkrief, MD

  CHU Tours

  PRINCIPAL INVESTIGATOR

• Lucy Meunier, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

• Fanny Lebosse, MD

  Hopital de la Croix-Rousse

  PRINCIPAL INVESTIGATOR

• Marie Noelle Hilleret, MD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 3, 2017
• Study Start: June 5, 2018
• Primary Completion: June 3, 2022
• Study Completion: March 20, 2023
• Last Updated: April 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)