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

NCT ID: NCT03069131

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-05
• Study Completion Date: 2023-03-20

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active rifaximin

Group Type: EXPERIMENTAL

Rifaximin

Intervention Type: DRUG

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

Rifaximin placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

twice daily administration of 1 rifaximin placebo tablet

Interventions

Rifaximin

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

Intervention Type: DRUG

Placebo

twice daily administration of 1 rifaximin placebo tablet

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alfasigma S.p.A.

INDUSTRY

Sponsor Role: collaborator

LC2 PHARMA

UNKNOWN

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rodolphe Anty, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Nice

Edouard Bardou-Jacquet, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Christophe Bureau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Vincent Di Martino, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU de Besançon

Claire Francoz, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Beaujon, Clichy

Alexandra Heurgue-Berlot, MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Reims

Marianne Latournerie, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Dijon

Alexandre Louvet, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU de Lille

Pierre Nahon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Jean Verdier, Bondy

Frédéric Oberti, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Isabelle Rosa-Hezode, MD

Role: PRINCIPAL_INVESTIGATOR

CHIC de Créteil

Marika Rudler, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Pitié-Salpêtrière, APHP

Matthieu Schnee, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital La Roche-sur-Yon

Ghassan Riachi, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Rouen

Isabelle Ollivier, MD

Role: PRINCIPAL_INVESTIGATOR

CHU CAEN

Eric Nguyen-Khac, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU Amiens

Laure Elkrief, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Tours

Lucy Meunier, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Fanny Lebosse, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital de la Croix-Rousse

Marie Noelle Hilleret, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

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, , France

Countries

France

References

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 Jul 11:S0168-8278(25)02318-9. doi: 10.1016/j.jhep.2025.06.019. Online ahead of print.

Reference Type: DERIVED

PMID: 40653111 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ProPILA-Rifax

Identifier Type: -

Identifier Source: org_study_id