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TerminatedNCT03469050ROADUpdated Oct 20, 2021

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

A Phase 2/3 interventional study of Rifaximin delayed released 400mg Tablet and Placebo in Diverticulitis, sponsored by Alfasigma S.p.A.. Terminated at 64 sites in 6 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-10-20.

Sponsored by Alfasigma S.p.A. · Phase 2/3, Interventional, and Prevention

Why this study was terminated
Sponsor's decision
Phase
Phase 2/3
Study type
Interventional
Enrollment
193
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Diverticulitis

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Keywords

  • Recurrent acute diverticulitis
  • Prevention
  • Diverticular complications
  • Rifaximin delayed release
  • Diverticulitis
  • SIBO
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
193 participants (actual)

Study arms

  • 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

  • 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 · Other: Placebo

  • 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

Interventions

  • DrugRifaximin delayed released 400mg Tablet

    Rifaximin delayed released

    Also known as: Rifaximin-EIR

  • OtherPlacebo

    Placebo BID + Placebo BID

05

What researchers measure

Primary outcomes

  1. Rate of patients with recurrence of diverticulitis and/or diverticular complications over the 12-month treatment period.

    Time frame: 12-month treatment period

Secondary outcomes

  1. 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]

    Time frame: 12-month treatment period

  2. Time to diverticulitis recurrence or complication

    Time frame: 12-month treatment period

  3. Rate of patients with diverticulitis-associated fever

    Time frame: 12-month treatment period

  4. Left-lower quadrant abdominal pain intensity

    Time frame: 12-month treatment period

  5. Left-lower quadrant abdominal pain duration

    Time frame: 12-month treatment period

  6. Number of days in a year with left-lower quadrant abdominal pain

    Time frame: 12-month treatment period

  7. Number of weeks in a year with episodes of prolonged (≥24 hours) left-lower quadrant abdominal pain

    Time frame: 12-month treatment period

  8. Number of days in a year with any abdominal pain

    Time frame: 12-month treatment period

  9. Number of weeks in a year with bloating

    Time frame: 12-month treatment period

  10. Change in bowel habits

    Evaluated by Bristol Stool Scale

    Time frame: 12-month treatment period

  11. Rate of any hospitalization for diverticulitis

    Time frame: 12-month treatment period

  12. Rate of hospitalization for diverticulitis without surgery

    Time frame: 12-month treatment period

  13. Rate of elective surgery for diverticulitis

    Time frame: 12-month treatment period

  14. Rate of emergency surgery for diverticulitis

    Time frame: 12-month treatment period

  15. Change in Quality of Life

    Evaluated by SF36 Quality of Life Questionnaire

    Time frame: 12-month treatment period

06

Study locations

64 sites
  • Hôpital Avicenne Service Gastro-entérologie
    Bobigny, France
  • Cabinet Médical
    Lille, France
  • Centre Hospitalier Regional Universitaire Claude Huriez Service de Chirurgie Digestive et Générale
    Lille, France
  • Hôpital Saint-Joseph Service Hépato-Gastroentérologie
    Marseille, France
  • CHU Nantes, Hôtel Dieu Clinique de Chirurgie digestive et endocrinienne (CCDE) Institut des maladies de l'Appareil Digestif (IMAD)
    Nantes, France
  • Hôpital Charles Nicolle - CHU Rouen Service Hépato-Gastroentérologie
    Rouen, France
  • Centre Hospitalier Universitaire (CHU) de Strasbourg Service de Chirurgie Digestive et Endocrinienne
    Strasbourg, France
  • Gemeinschaftspraxis - Praxis Überruhr
    Essen, Germany
  • Medamed GmbH Studienambulanz Leipzig
    Leipzig, Germany
  • MVZ Dres. Eisenbach, Simon, Schwarz
    Leverkusen, Germany
  • Gemeinschaftspraxis Dres. Balck
    Meine, Germany
  • Praxis Dres. med. Naudts und Nowack
    Rodgau, Germany
  • Ospedale Cardinal Massaia SOC Gastroenterologia ed Endoscopia Digestiva
    Asti, Italy
  • Ospedale Civile S. Agostino Estense - Divisione di Endoscopia Digestiva
    Baggiovara, 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
    Bari, Italy
  • AOU di Bologna - Policlinico S.Orsola Malpighi - Dipartimento di Scienze Mediche e Chirurgiche
    Bologna, Italy
  • AOU Cagliari - Policlinico Monserrato Gastroenterologia
    Cagliari, Italy
  • Azienda Ospedaliera Garibaldi Unità Operativa Complessa di Gastroenterologia
    Catania, Italy
  • Ospedale Ciaccio - De Lellis Divisione di Gastroenterologia ed Endoscopia Digestiva
    Catanzaro, Italy
  • Policlinico Ss Annunziata - ASL 2 Lanciano Vasto Chieti UOSD Endoscopia Digestiva
    Chieti, Italy
  • Ospedale Valduce Unità Operativa Complessa di Gastroenterologia
    Como, Italy
  • Ospedale S. Salvatore di L'Aquila Unità Operativa di Gastroenterologia, Epatologia e Nutrizione
    Coppito, Italy
  • Ospedale Civile San Giovanni di Dio - Divisione di Gastroenterologia ed Endoscopia Digestiva
    Crotone, 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
    Genova, Italy
  • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
    Milano, Italy
  • UNIMI - San Paolo (ASST Santi Paolo e Carlo) Medicina Generale
    Milano, Italy
  • Ospedale San Gerardo Endoscopia Digestiva
    Monza, 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
    Napoli, Italy
  • AOU di Padova Unità Operativa Complessa di Gastroenterologia
    Padova, Italy
  • Ospedale Buccheri La Ferla Fetebenefratelli Unità Operativa di Gastroenterologia e Endoscopia Digestiva
    Palermo, Italy
  • Fondazione IRCCS Policlinico San Matteo Dipartimento di Medicina Interna
    Pavia, Italy
  • PO Cisanello - AOU Pisana Unità Operativa Complessa di Gastroenterologia - AOUP Gastroenterologia Universitaria
    Pisa, Italy
  • Ospedale Popoli Unità Operativa Semplice Dipartimentale Chirurgia Endoscopica
    Popoli, 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
    Roma, Italy
  • Istituto Clinico Humanitas-Unità Operativa Malattie Infiammatorie Croniche Intestinali
    Rozzano, Italy
  • AOU OO. RR. San Giovanni di Dio e Ruggi d'Aragona - Dipartimento di Medicina e Chirurgia - Gastroenterologia
    Salerno, Italy
  • IRCCS Policlinico San Donato Unità Operativa Medicina Generale III, Gastroenterologia
    San Donato Milanese, Italy
  • Ospedale Sant'Anna Unità Operativa di Medicina Interna
    San Fermo Della Battaglia, Italy
  • Azienda Ospedaliera San Giovanni Battista Molinette - S.C. Gastroenterologia e Epatologia
    Torino, Italy
  • Ospedale di Circolo e Fondazione Macchi Endoscopia
    Varese, Italy
  • Azienda Ospedaliera Universitaria Integrata - UOC Gastroenterologia A- Borgo Trento-Dipartimento Medicina Generale
    Verona, Italy
  • Meander Medisch Centrum Surgery
    Amersfoort, Netherlands
  • VU Medisch Centrum Gastroenterology
    Amsterdam, Netherlands
  • Ikazia ziekenhuis Gastroenterology
    Rotterdam, Netherlands
  • Hospital General Universitario de Alicante Servicio de Aparato Digestivo
    Alicante, 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
    Barcelona, Spain
  • Hospital Universitario de Belltvitge Servicio de Cirugía General y Digestiva
    Hospitalet de Llobregat, Spain
  • Hospital General San Jorge de Huesca Servicio de Aparato Digestivo
    Huesca, Spain
  • Hospital Costa del Sol Servicio Digestivo
    Marbella, Spain
  • Hospital de Ourense Servicio de Aparato Digestivo
    Orense, Spain
  • Hospital Universitario de Canarias Servicio de Gastroenterología
    Santa Cruz De Tenerife, Spain
  • Hospital Clínico Universitario Lozano Blesa Servicio de Aparato Digestivo
    Zaragoza, Spain
  • Yeovil District Hospital NHS Trust Department of Surgery
    Yeovil, United Kingdom
07

Registry details

Key details

Study ID
NCT03469050
Lead sponsor
Alfasigma S.p.A.
Responsible party
Sponsor
First posted
Mar 19, 2018
Start date
Jul 2, 2018
Primary completion
Dec 22, 2020
Completion
Dec 22, 2020
Last update
Oct 20, 2021

Study contacts

Alessandro Blè, MD
study director · Alfasigma S.p.A.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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