Clinical trial NCT03469050: Rifaximin Delayed Release for the Prevention of Recurrent Acute Diverticulitis and Diverticular Complications.
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Diverticulitis
Keywords: Recurrent acute diverticulitis
Prevention
Diverticular complications
Rifaximin delayed release
Diverticulitis
SIBO
Lead sponsor: Alfasigma S.p.A.
Sponsor class: INDUSTRY
First posted: 2018-03-19
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a phase II, multicenter, double-blind, placebo-controlled, randomized clinical trial.
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of patients with recurrence of diverticulitis and/or diverticular complications over the 12-month treatment period.
timeFrame: 12-month treatment period
Secondary outcomes:
measure: 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]
timeFrame: 12-month treatment period
measure: Time to diverticulitis recurrence or complication
timeFrame: 12-month treatment period
measure: Rate of patients with diverticulitis-associated fever
timeFrame: 12-month treatment period
measure: Left-lower quadrant abdominal pain intensity
timeFrame: 12-month treatment period
measure: Left-lower quadrant abdominal pain duration
timeFrame: 12-month treatment period
measure: Number of days in a year with left-lower quadrant abdominal pain
timeFrame: 12-month treatment period
measure: Number of weeks in a year with episodes of prolonged (≥24 hours) left-lower quadrant abdominal pain
timeFrame: 12-month treatment period
measure: Number of days in a year with any abdominal pain
timeFrame: 12-month treatment period
measure: Number of weeks in a year with bloating
timeFrame: 12-month treatment period
measure: Change in bowel habits
timeFrame: 12-month treatment period
measure: Rate of any hospitalization for diverticulitis
timeFrame: 12-month treatment period
measure: Rate of hospitalization for diverticulitis without surgery
timeFrame: 12-month treatment period
measure: Rate of elective surgery for diverticulitis
timeFrame: 12-month treatment period
measure: Rate of emergency surgery for diverticulitis
timeFrame: 12-month treatment period
measure: Change in Quality of Life
timeFrame: 12-month treatment period
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne Service Gastro-entérologie
city: Lille
country: France
facility: Cabinet Médical
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire Claude Huriez Service de Chirurgie Digestive et Générale
city: Marseille
country: France
facility: Hôpital Saint-Joseph Service Hépato-Gastroentérologie
city: Nantes
country: France
facility: CHU Nantes, Hôtel Dieu Clinique de Chirurgie digestive et endocrinienne (CCDE) Institut des maladies de l'Appareil Digestif (IMAD)
city: Rouen
country: France
facility: Hôpital Charles Nicolle - CHU Rouen Service Hépato-Gastroentérologie
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire (CHU) de Strasbourg Service de Chirurgie Digestive et Endocrinienne
city: Essen
country: Germany
facility: Gemeinschaftspraxis - Praxis Überruhr
city: Leipzig
country: Germany
facility: Medamed GmbH Studienambulanz Leipzig
city: Leverkusen
country: Germany
facility: MVZ Dres. Eisenbach, Simon, Schwarz
city: Meine
country: Germany
facility: Gemeinschaftspraxis Dres. Balck
city: Rodgau
country: Germany
facility: Praxis Dres. med. Naudts und Nowack
city: Asti
country: Italy
facility: Ospedale Cardinal Massaia SOC Gastroenterologia ed Endoscopia Digestiva
city: Baggiovara
country: Italy
facility: Ospedale Civile S. Agostino Estense - Divisione di Endoscopia Digestiva
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Consorziale di Bari Dipartimento di Gastroenterologia
city: Bari
country: Italy
facility: Ospedale "San Paolo" - Unità Operativa Complessa di Gastroenterologia ed Endoscopia Digestiva
city: Bari
country: Italy
facility: Università degli Studi di Bari Policlinico Medicina Interna
city: Bologna
country: Italy
facility: AOU di Bologna - Policlinico S.Orsola Malpighi - Dipartimento di Scienze Mediche e Chirurgiche
city: Cagliari
country: Italy
facility: AOU Cagliari - Policlinico Monserrato Gastroenterologia
city: Catania
country: Italy
facility: Azienda Ospedaliera Garibaldi Unità Operativa Complessa di Gastroenterologia
city: Catanzaro
country: Italy
facility: Ospedale Ciaccio - De Lellis Divisione di Gastroenterologia ed Endoscopia Digestiva
city: Chieti
country: Italy
facility: Policlinico Ss Annunziata - ASL 2 Lanciano Vasto Chieti UOSD Endoscopia Digestiva
city: Como
country: Italy
facility: Ospedale Valduce Unità Operativa Complessa di Gastroenterologia
city: Coppito
country: Italy
facility: Ospedale S. Salvatore di L'Aquila Unità Operativa di Gastroenterologia, Epatologia e Nutrizione
city: Crotone
country: Italy
facility: Ospedale Civile San Giovanni di Dio - Divisione di Gastroenterologia ed Endoscopia Digestiva
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedali Galliera Chirurgia Generale
city: Genova
country: Italy
facility: Ospedale Policlinico S.Martino Istituto di Ricovero e Cura per l'Oncologia Dipartimento di Medicina Interna e Specialità Mediche U.O. Clinica Gastroenterologica
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: UNIMI - San Paolo (ASST Santi Paolo e Carlo) Medicina Generale
city: Monza
country: Italy
facility: Ospedale San Gerardo Endoscopia Digestiva
city: Napoli
country: Italy
facility: AOU Seconda Università degli Studi di Napoli Unità Operativa Complessa di Epato-Gastroenterologia
city: Napoli
country: Italy
facility: Policlinico Federico II - UO di Epatogastroenterologia ed endoscopia digestiva
city: Napoli
country: Italy
facility: Policlinico Federico II - UOSD Diagnosi Fisiopatologica e Terapia delle Malattie Motorie Digestive
city: Padova
country: Italy
facility: AOU di Padova Unità Operativa Complessa di Gastroenterologia
city: Palermo
country: Italy
facility: Ospedale Buccheri La Ferla Fetebenefratelli Unità Operativa di Gastroenterologia e Endoscopia Digestiva
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo Dipartimento di Medicina Interna
city: Pisa
country: Italy
facility: PO Cisanello - AOU Pisana Unità Operativa Complessa di Gastroenterologia - AOUP Gastroenterologia Universitaria
city: Popoli
country: Italy
facility: Ospedale Popoli Unità Operativa Semplice Dipartimentale Chirurgia Endoscopica
city: Roma
country: Italy
facility: Azienda Ospedaliera San Giovanni Addolorata Gastroenterologia ed Endoscopia Digestiva
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli Unità Operativa Complessa di Gastroenterologia e Malattie del Fegato
city: Roma
country: Italy
facility: Ospedale Cristo Re - Divisione di Medicina Interna e Gastroenterologia
city: Roma
country: Italy
facility: Ospedale Sant'Andrea - Gastroenterologia
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico Unità Operativa Complessa di Gastroenterologia ed Endoscopia Digestiva
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas-Unità Operativa Malattie Infiammatorie Croniche Intestinali
city: Salerno
country: Italy
facility: AOU OO. RR. San Giovanni di Dio e Ruggi d'Aragona - Dipartimento di Medicina e Chirurgia - Gastroenterologia
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato Unità Operativa Medicina Generale III, Gastroenterologia
city: San Fermo Della Battaglia
country: Italy
facility: Ospedale Sant'Anna Unità Operativa di Medicina Interna
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista Molinette - S.C. Gastroenterologia e Epatologia
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi Endoscopia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata - UOC Gastroenterologia A- Borgo Trento-Dipartimento Medicina Generale
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum Surgery
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum Gastroenterology
city: Rotterdam
country: Netherlands
facility: Ikazia ziekenhuis Gastroenterology
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante Servicio de Aparato Digestivo
city: Barcelona
country: Spain
facility: Centre Médic Teknon Servicio de Aparato Digestivo
city: Barcelona
country: Spain
facility: Hospital Clínic Servicio de Gastroenterología
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón Servicio de Aparato Digestivo
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Belltvitge Servicio de Cirugía General y Digestiva
city: Huesca
country: Spain
facility: Hospital General San Jorge de Huesca Servicio de Aparato Digestivo
city: Marbella
country: Spain
facility: Hospital Costa del Sol Servicio Digestivo
city: Orense
country: Spain
facility: Hospital de Ourense Servicio de Aparato Digestivo
city: Santa Cruz De Tenerife
country: Spain
facility: Hospital Universitario de Canarias Servicio de Gastroenterología
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa Servicio de Aparato Digestivo
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital NHS Trust Department of Surgery
Study officials:
affiliation: Alfasigma S.p.A.
name: Alessandro Blè, MD
role: STUDY_DIRECTOR
References: