Rifaximin Delayed Release for the Prevention of Recurrent Acute Diverticulitis and Diverticular Complications. (ROAD)

Rifaximin Delayed Release (400 mg Tablet) for the Prevention of Recurrent Acute Diverticulitis and Diverticular Complications. A Phase II, Multicenter, Double-blind, Placebo-controlled, Randomized Clinical Trial

Colonic microbiota changes may play a key role in the pathogenesis of acute diverticulitis. A previous proof-of-concept study suggests that rifaximin, a low-absorbable oral antibiotic, may be beneficial for prevention of acute diverticulitis recurrence by modulating the gut microflora.

The main objective of this study is to evaluate the safety and efficacy of two different doses of a delayed release formulation of rifaximin, versus placebo, for the prevention of recurrence of acute diverticulitis and diverticular complications in patients with a recent episode of acute diverticulitis.

Study Overview

• Status: Terminated
• Conditions: Diverticulitis
• Intervention / Treatment: Drug: Rifaximin delayed released 400mg Tablet; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Bobigny, France
    • Hôpital Avicenne Service Gastro-Entérologie
  • Lille, France
    • Cabinet Médical
  • Lille, France
    • Centre Hospitalier Regional Universitaire Claude Huriez Service de Chirurgie Digestive et Générale
  • Marseille, France
    • Hôpital Saint-Joseph Service Hépato-Gastroentérologie
  • Nantes, France
    • CHU Nantes, Hôtel Dieu Clinique de Chirurgie digestive et endocrinienne (CCDE) Institut des maladies de l'Appareil Digestif (IMAD)
  • Rouen, France
    • Hôpital Charles Nicolle - CHU Rouen Service Hépato-Gastroentérologie
  • Strasbourg, France
    • Centre Hospitalier Universitaire (CHU) de Strasbourg Service de Chirurgie Digestive et Endocrinienne
• Germany
  • Essen, Germany
    • Gemeinschaftspraxis - Praxis Überruhr
  • Leipzig, Germany
    • Medamed GmbH Studienambulanz Leipzig
  • Leverkusen, Germany
    • MVZ Dres. Eisenbach, Simon, Schwarz
  • Meine, Germany
    • Gemeinschaftspraxis Dres. Balck
  • Rodgau, Germany
    • Praxis Dres. med. Naudts und Nowack
• Italy
  • Asti, Italy
    • Ospedale Cardinal Massaia SOC Gastroenterologia ed Endoscopia Digestiva
  • Baggiovara, Italy
    • Ospedale Civile S. Agostino Estense - Divisione di Endoscopia Digestiva
  • Bari, Italy
    • Azienda Ospedaliera Policlinico Consorziale di Bari Dipartimento di Gastroenterologia
  • Bari, Italy
    • Ospedale "San Paolo" - Unità Operativa Complessa di Gastroenterologia ed Endoscopia Digestiva
  • Bari, Italy
    • Università degli Studi di Bari Policlinico Medicina Interna
  • Bologna, Italy
    • AOU di Bologna - Policlinico S.Orsola Malpighi - Dipartimento di Scienze Mediche e Chirurgiche
  • Cagliari, Italy
    • AOU Cagliari - Policlinico Monserrato Gastroenterologia
  • Catania, Italy
    • Azienda Ospedaliera Garibaldi Unità Operativa Complessa di Gastroenterologia
  • Catanzaro, Italy
    • Ospedale Ciaccio - De Lellis Divisione di Gastroenterologia ed Endoscopia Digestiva
  • Chieti, Italy
    • Policlinico Ss Annunziata - ASL 2 Lanciano Vasto Chieti UOSD Endoscopia Digestiva
  • Como, Italy
    • Ospedale Valduce Unità Operativa Complessa di Gastroenterologia
  • Coppito, Italy
    • Ospedale S. Salvatore di L'Aquila Unità Operativa di Gastroenterologia, Epatologia e Nutrizione
  • Crotone, Italy
    • Ospedale Civile San Giovanni di Dio - Divisione di Gastroenterologia ed Endoscopia Digestiva
  • Genova, Italy
    • Ente Ospedaliero Ospedali Galliera Chirurgia Generale
  • Genova, Italy
    • Ospedale Policlinico S.Martino Istituto di Ricovero e Cura per l'Oncologia Dipartimento di Medicina Interna e Specialità Mediche U.O. Clinica Gastroenterologica
  • Milano, Italy
    • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
  • Milano, Italy
    • UNIMI - San Paolo (ASST Santi Paolo e Carlo) Medicina Generale
  • Monza, Italy
    • Ospedale San Gerardo Endoscopia Digestiva
  • Napoli, Italy
    • AOU Seconda Università degli Studi di Napoli Unità Operativa Complessa di Epato-Gastroenterologia
  • Napoli, Italy
    • Policlinico Federico II - UO di Epatogastroenterologia ed endoscopia digestiva
  • Napoli, Italy
    • Policlinico Federico II - UOSD Diagnosi Fisiopatologica e Terapia delle Malattie Motorie Digestive
  • Padova, Italy
    • AOU di Padova Unità Operativa Complessa di Gastroenterologia
  • Palermo, Italy
    • Ospedale Buccheri La Ferla Fetebenefratelli Unità Operativa di Gastroenterologia e Endoscopia Digestiva
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo Dipartimento di Medicina Interna
  • Pisa, Italy
    • PO Cisanello - AOU Pisana Unità Operativa Complessa di Gastroenterologia - AOUP Gastroenterologia Universitaria
  • Popoli, Italy
    • Ospedale Popoli Unità Operativa Semplice Dipartimentale Chirurgia Endoscopica
  • Roma, Italy
    • Azienda Ospedaliera San Giovanni Addolorata Gastroenterologia ed Endoscopia Digestiva
  • Roma, Italy
    • Fondazione Policlinico Universitario A. Gemelli Unità Operativa Complessa di Gastroenterologia e Malattie del Fegato
  • Roma, Italy
    • Ospedale Cristo Re - Divisione di Medicina Interna e Gastroenterologia
  • Roma, Italy
    • Ospedale Sant'Andrea - Gastroenterologia
  • Roma, Italy
    • Policlinico Universitario Campus Biomedico Unità Operativa Complessa di Gastroenterologia ed Endoscopia Digestiva
  • Rozzano, Italy
    • Istituto Clinico Humanitas-Unità Operativa Malattie Infiammatorie Croniche Intestinali
  • Salerno, Italy
    • AOU OO. RR. San Giovanni di Dio e Ruggi d'Aragona - Dipartimento di Medicina e Chirurgia - Gastroenterologia
  • San Donato Milanese, Italy
    • IRCCS Policlinico San Donato Unità Operativa Medicina Generale III, Gastroenterologia
  • San Fermo Della Battaglia, Italy
    • Ospedale Sant'Anna Unità Operativa di Medicina Interna
  • Torino, Italy
    • Azienda Ospedaliera San Giovanni Battista Molinette - S.C. Gastroenterologia e Epatologia
  • Varese, Italy
    • Ospedale di Circolo e Fondazione Macchi Endoscopia
  • Verona, Italy
    • Azienda Ospedaliera Universitaria Integrata - UOC Gastroenterologia A- Borgo Trento-Dipartimento Medicina Generale
• Netherlands
  • Amersfoort, Netherlands
    • Meander Medisch Centrum Surgery
  • Amsterdam, Netherlands
    • VU Medisch Centrum Gastroenterology
  • Rotterdam, Netherlands
    • Ikazia ziekenhuis Gastroenterology
• Spain
  • Alicante, Spain
    • Hospital General Universitario de Alicante Servicio de Aparato Digestivo
  • Barcelona, Spain
    • Centre Médic Teknon Servicio de Aparato Digestivo
  • Barcelona, Spain
    • Hospital Clínic Servicio de Gastroenterología
  • Barcelona, Spain
    • Hospital Vall d'Hebrón Servicio de Aparato Digestivo
  • Hospitalet de Llobregat, Spain
    • Hospital Universitario de Belltvitge Servicio de Cirugía General y Digestiva
  • Huesca, Spain
    • Hospital General San Jorge de Huesca Servicio de Aparato Digestivo
  • Marbella, Spain
    • Hospital Costa del Sol Servicio Digestivo
  • Orense, Spain
    • Hospital de Ourense Servicio de Aparato Digestivo
  • Santa Cruz De Tenerife, Spain
    • Hospital Universitario de Canarias Servicio de Gastroenterología
  • Zaragoza, Spain
    • Hospital Clínico Universitario Lozano Blesa Servicio de Aparato Digestivo
• United Kingdom
  • Yeovil, United Kingdom
    • Yeovil District Hospital NHS Trust Department of Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Men and women aged 18-80 years at screening.
• Female participants must be either of non-childbearing potential or of childbearing potential with a negative pregnancy test result at screening and randomization AND agreeing to use a highly effective method of contraception.
• A previous documented episode of diverticulitis between 30 and 180 days prior to screening.
• Clinical remission from acute diverticulitis at screening

Key Exclusion Criteria:

• History of two or more acute diverticulitis episodes or history of any diverticular complication.
• Any documented current organic disease of the gastrointestinal tract other than diverticulosis
• Laboratory signs of clinically significant acute inflammation or signs/symptoms of diverticular complications.
• Diagnosis or history of inflammatory bowel disease (or other conditions associated with ulcerative lesions of the intestinal tract).
• Patients with positive Clostridium difficile toxin stool assay.
• Use of marketed rifaximin (or neomycin or other low-absorbable oral antibiotics) during or after the previous episode of acute diverticulitis.
• Severe hepatic impairment
• Severe kidney impairment
• Any other current significant health condition that in the Investigator's judgement may: i) jeopardize the patient's safe participation in the trial or ii) make unlikely the patient's completion of the study or iii) make unlikely the patient's compliance with the study procedures.
• History of hypersensitivity to rifaximin, rifamycin-derivatives or any of the rifaximin delayed release or placebo excipients.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin delayed released 800 mg b.i.d.; (i.e. 2 x 400 mg tablet twice a day; total daily dose: 1600 mg) for 10 consecutive days a month, for 12 months	Drug: Rifaximin delayed released 400mg Tablet; Rifaximin delayed released; Other Names: Rifaximin-EIR
Experimental: Rifaximin delayed released 400 mg b.i.d; (i.e. 1x400 mg tablet plus 1 placebo tablet twice a day; total daily dose: 800 mg) for 10 consecutive days a month, for 12 months	Drug: Rifaximin delayed released 400mg Tablet; Rifaximin delayed released; Other Names: Rifaximin-EIR; Other: Placebo; Placebo BID + Placebo BID
Placebo Comparator: Placebo b.i.d.; (i.e. 2 x placebo tablets twice a day) for 10 consecutive days a month, for 12 months.	Other: Placebo; Placebo BID + Placebo BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of patients with recurrence of diverticulitis and/or diverticular complications over the 12-month treatment period.	12-month treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with an acute episode of prolonged (≥24 hours) left-lower quadrant abdominal pain plus leukocytosis/elevation of CRP [Time Frame: 12-month treatment period]		12-month treatment period
Time to diverticulitis recurrence or complication		12-month treatment period
Rate of patients with diverticulitis-associated fever		12-month treatment period
Left-lower quadrant abdominal pain intensity		12-month treatment period
Left-lower quadrant abdominal pain duration		12-month treatment period
Number of days in a year with left-lower quadrant abdominal pain		12-month treatment period
Number of weeks in a year with episodes of prolonged (≥24 hours) left-lower quadrant abdominal pain		12-month treatment period
Number of days in a year with any abdominal pain		12-month treatment period
Number of weeks in a year with bloating		12-month treatment period
Change in bowel habits	Evaluated by Bristol Stool Scale	12-month treatment period
Rate of any hospitalization for diverticulitis		12-month treatment period
Rate of hospitalization for diverticulitis without surgery		12-month treatment period
Rate of elective surgery for diverticulitis		12-month treatment period
Rate of emergency surgery for diverticulitis		12-month treatment period
Change in Quality of Life	Evaluated by SF36 Quality of Life Questionnaire	12-month treatment period

Collaborators and Investigators

• Sponsor: Alfasigma S.p.A.
• Investigators: Study Director: Alessandro Blè, MD, Alfasigma S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 12, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Prevention; Diverticulitis; SIBO; Recurrent acute diverticulitis; Diverticular complications; Rifaximin delayed release
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Diverticular Diseases; Diverticulitis; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: REDIV/002/17; 2017-002708-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No