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

Sponsor
Centre Hospitalier Universitaire de Besancon (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03069131
Collaborator
Alfasigma S.p.A. (Industry), LC2 PHARMA (Other)
160
18
2
68.4
8.9
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 20, 2018
Actual Primary Completion Date :
Jun 5, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active rifaximin

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

Placebo Comparator: Rifaximin placebo

Other: Placebo
twice daily administration of 1 rifaximin placebo tablet

Outcome Measures

Primary Outcome Measures

  1. death [12 months]

    record of death whatever the cause

Secondary Outcome Measures

  1. Hospital mortality rate and mortality rate at 3 months [3 months]

    survival during hospitalization and at 3 months

  2. Hospital mortality rate and mortality rate at 6 months [6 months]

    survival during hospitalization and at 6 months

  3. Incidence of spontaneous bacterial peritonitis during follow-up [12 months]

    Bacterial analysis of ascites

  4. Incidence of the other complications of liver cirrhosis during follow-up [12 months]

    complications of liver cirrhosis : HE, gastrointestinal bleeding and hepatorenal syndrome

  5. Patient hospitalizations during follow-up [12 months]

    number of days of hospitalization during 12 months of follow-up

  6. Quantitative variations of IL-6 in serum between day 1 and day 30 [1 month]

    Dosage of IL-6 in serum at D1 and D30

  7. Quantitative variations of lipopolysaccharides (LPS) in serum between day 1 and day 30 [1 month]

    Dosage of LPS in serum at D1 and D30

  8. Quantitative variations of copeptin in serum between day 1 and day 30 [1 month]

    Dosage of copeptin in serum at D1 and D30

  9. Quantitative variations of CRP in serum between day 1 and day 30 [1 month]

    Dosage of CRP in serum at D1 and D30

  10. Quantitative variations of von Willebrand Factor antigen in serum between day 1 and day 30 [1 month]

    Dosage of von Willebrand Factor antigen in serum at D1 and D30

  11. Composition of the intestinal microbiota [up to 18 months]

    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

  12. Safety analysis of the study drug [12 months]

    Record of adverse events and serious adverse events in each arm

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 CHU Amiens Amiens France 80054
2 CHU d'Angers Angers France
3 CHU de Besançon Besançon France
4 Hôpital Jean Verdier Bondy France
5 CHU Caen Caen France 14033
6 Hôpital Beaujon Clichy France
7 CHIC de Créteil Créteil France
8 CHU Grenoble La Tronche France 38700
9 CHRU de Lille Lille France
10 Hopital de la croix-rousse Lyon France 69004
11 CHU Montpellier Montpellier France 34295
12 CHU de Nice Nice France
13 Hôpital Pitié Salpêtrière Paris France
14 CHU de Reims Reims France
15 CHU de Rennes Rennes France
16 CHU Rouen Rouen France 76031
17 CHU de Toulouse Toulouse France
18 CHU Tours Tours France 37044

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier:
NCT03069131
Other Study ID Numbers:
  • ProPILA-Rifax
First Posted:
Mar 3, 2017
Last Update Posted:
Jul 13, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Centre Hospitalier Universitaire de Besancon
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 13, 2022