Prevention of Recurrence of Diverticulitis (PREVENT1)

A Phase III, Randomised, Double-Blind, Dose-Response, Stratified, Placebo-Controlled Study Evaluating the Safety and Efficacy of SPD476 Versus Placebo Over 104 Weeks in the Prevention of Recurrence of Diverticulitis.

The purpose of this study is to determine whether SPD476 is effective in reducing recurrence of diverticulitis.

Study Overview

• Status: Completed
• Conditions: Diverticulitis
• Intervention / Treatment: Drug: SPD476 (1.2g); Drug: SPD476 (2.4 g); Drug: SPD476 (4.8 g); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 590
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1180AAX
    • Sanatorio Güemes
  • Buenos Aires, Argentina, B1657BHD
    • Hospital Bocalandro
  • Buenos Aires, Argentina, B1722FJN
    • Hospital Héroes de Malvinas
  • Buenos Aires, Argentina, C1117AAA
    • GEDYT
  • Santa Fe, Argentina, S2000BCG
    • Cibic S.A.
  • Buenos Aires
    • Lanus, Buenos Aires, Argentina, B1824KAS
      • CIMeL
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DFD
      • Instituto Gamma
• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
  • Camperdown, Australia, 2050
    • Royal Prince Albert Hospital
  • Frankston, Australia, 3199
    • Frankston Private
  • Frankston, Australia, VIC 3199
    • Bayside Gastroenterology
  • Fremantle, Australia, 6160
    • Fremantle Hospital
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • The Canberra Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Base Hospital
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital (Melb) LTD
• Colombia
  • Barranquilla, Colombia
    • Ugasend S.A
  • Bogota, Colombia
    • Hospital Universitario San Ignacio
  • Bogota, Colombia
    • Clinica Colsinatas SA
  • Bogota, Colombia
    • FOQUS, Centro de Investigacion Clinica
  • Bogota, Colombia
    • Fundación Clinica Abood Shaio
  • Medellin, Colombia
    • Clínica Las Américas
• France
  • Lille, France, 59000
    • Cabinet du Dr Olivier Delette
  • Paris, France, 75017
    • Dr Michel Regensberg
  • Alsace
    • Strasbourg, Alsace, France, 67200
      • CHU de Strasbourg
  • Brittany
    • Nantes, Brittany, France, 44033
      • Hepato Gastro Enterology
  • Normandy
    • Rouen, Normandy, France, 76031
      • Hôpital Charles Nicolle
  • Paris
    • Clichy, Paris, France, 92118
      • Hôpital Beaujon
  • Picardie
    • Saint Quentin, Picardie, France, 02100
      • Cabinet de Gastro-enterologie du Dr Alain Thevenin
  • Provence-Alpes-Côte d'Azur
    • Nice, Provence-Alpes-Côte d'Azur, France, 06200
      • Hopital I'Archet
  • Provence-Alpes-Côte-d'Azur
    • Marseille, Provence-Alpes-Côte-d'Azur, France, 13000
      • Clinique Bouchard
  • Rhone-Alpes
    • Grenoble, Rhone-Alpes, France, 38043
      • CHU de Grenoble
• India
  • Ahmedabad, India, 380006
    • Brahmin Mitra Mandal Society
  • Pune, India, 411 001
    • Ruby Hall Clinic
  • Secunderabad, India, 500 003
    • Krishna Institute of Medical Sciences
  • Kerala
    • Calicut, Kerala, India, 673004
      • Baby Memorial Hospital
    • Cochin, Kerala, India, 682304
      • Lakeshore Hospital & Research Centre Ltd
    • Trivandrum, Kerala, India, 695607
      • Sree Gokulam Medical College and Research Foundation
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Dayanand Medical College and Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India
      • S R Kalla Memorial Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600020
      • Aceer
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • Institute of Postgraduate Medical Education and Research
• Israel
  • Afula, Israel, 18101
    • Emek Medical Center
  • Ashkelon, Israel, 78278
    • Barzilai Medical Centre
  • Beer Sheva, Israel, 84101
    • Soroka Medical Center
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 63106
    • Rambam Medical Center
  • Jerusalem, Israel
    • Hadassah Ein-Karem Medical Center
  • Kfar-Saba, Israel
    • Meir Medical Centre
  • Petah-Tikva, Israel, 49100
    • Rabin Medical Center
  • Rechovot, Israel
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • The Tel Aviv Sourasky Medical Center
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center
  • Zerifin, Israel, 70300
    • Assaf Harofeh Medical Center
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
  • Christchurch, New Zealand
    • CURT Medical Trials Trust Board
  • Dunedin, New Zealand
    • Dunedin Hospital
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
  • Tauranga, New Zealand
    • Tauranga Hospital
  • Auckland
    • Takapuna, Auckland, New Zealand
      • Shakespeare Specialist Group
• Spain
  • Barcelona, Spain, 08035
    • Hospital Valle de Hebron
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Palma de Mallorca, Spain, 07014
    • Hospital Son Dureta
  • San Sebastian, Spain, 20014
    • Hospital de Donostia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• Sweden
  • Goteborg, Sweden, 41685
    • University Hospital/Eastern Hospital
  • Linköping, Sweden, 58185
    • University Hospital Linköping
  • Stockholm, Sweden, 18288
    • Danderyd Hospital
  • Stockholm, Sweden, 17176
    • Karolinska university Hospital
  • Stockholm, Sweden, 11883
    • VO Internmedicin
  • Uppsala, Sweden
    • Kirurgkliniken
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, SW10 9NH
    • Chelsea & Westminster Hospital
  • London, United Kingdom, W12 0NN
    • Imperial College London
  • East Anglia
    • Norwich, East Anglia, United Kingdom, NR4 7UY
      • Norfolk/Norwich University Hospital
  • London
    • Harrow, London, United Kingdom, HA1 3UJ
      • St Mark's Hospital
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Dedicated Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Lynn Institute of the Ozarks
  • California
    • Anaheim, California, United States, 92108
      • Advanced Clinical Research Institute
    • Chula Vista, California, United States, 91910
      • GW Research
    • Monterey, California, United States, 93940
      • Monterey Bay GI Research Institute, Inc
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga C. Trials
    • Roseville, California, United States, 95661
      • Clinical Trials Research
    • San Diego, California, United States, 92123
      • Medical Associates Research
    • Torrance, California, United States, 90505
      • Torrance Clinical Research
  • Colorado
    • Thornton, Colorado, United States, 80229
      • Rocky Mountain Gastroenterology Associates
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Gastroenterology Associates of Fairfield County
    • New Haven, Connecticut, United States, 06520
      • Yale Center for Clinical Investigation
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Zasa Clinical Research
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Orlando, Florida, United States, 32806
      • Compass Research
    • Port Orange, Florida, United States, 32129
      • Accord Clinic Research, LLC
    • Tampa, Florida, United States, 33613
      • Florida Medical Clinic/Tampa Clinical Trials
  • Georgia
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates Of Central Georgia, LLC
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Research Institute
  • Iowa
    • Clive, Iowa, United States, 50325
      • Digestive & Liver Disease Consultants
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • New Orleans Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates
    • Towson, Maryland, United States, 21204
      • Endoscopic Microsurgery Associates, PA
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Research Institute
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Jefferson City Medical Group
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • South Jersey Gastroenterology, P.A.
    • Ocean City, New Jersey, United States, 07712
      • Howard Guss, DO
    • Passaic, New Jersey, United States, 07055
      • New Jersey Physicians, LLC
    • Voorhees, New Jersey, United States, 08043
      • Allied Gastrointestinal Associates, P.A.
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group
    • New York, New York, United States, 10075
      • Research Associates of New York
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Vital Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gastroenterology Specialists, Inc
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Research Center
    • Kingsport, Tennessee, United States, 37660
      • Gastroenterology Associates Clinical Research
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Harris Methodist Fort Worth Hospital
    • Houston, Texas, United States, 77005
      • Kelsey-Seybold Clinic
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78258
      • Stone Oak Research Foundation
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Advanced Healthcare, Inc. - Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females =>18yrs of age.
2. If female of childbearing potential (FOCP), has demonstrated a negative beta HCG (human chorionic gonadotropin) serum pregnancy test, and agrees to comply with any applicable contraceptive requirements of the protocol.
3. An episode of acute diverticulitis that resolved without colonic resection.
4. Confirmation of diverticulosis via endoscopic evaluation of the sigmoid colon with at least three diverticula noted.

Exclusion Criteria:

1. Previous colorectal surgery, including surgical intervention for diverticular disease (with the exception of haemorrhoidectomy, colonic removal of polyps, and appendectomy)
2. Active peptic ulcer disease
3. History of or current presence of inflammatory bowel disease (IBD)
4. Subjects with active irritable bowel syndrome (IBS) requiring ongoing medication
5. Allergy or hypersensitivity to aspirin or related compounds
6. Allergy to radiologic contrast agents
7. Use of another Investigational product within 30 days of Baseline
8. Use of antibiotic therapy within 4 weeks of Baseline
9. Within 14 days of Baseline, use of prebiotic, probiotic or 5-ASA medications, as well as drugs active at the 5HT-receptor or anti-spasmodic agents
10. Use of systemic or rectal steroids within 6 weeks of Baseline. Use of inhaled or nasal steroids is acceptable
11. Use of anti-inflammatory drugs, (NSIADs, COX-2 inhibitors) including aspirin (except for cardiac prophylaxis) and ibuprofen, on a regular and ongoing basis
12. History of alcohol or other substance abuse within the previous year
13. Active or recent history of endometriosis or dysmenorrhoea within 6 months prior to Baseline
14. Females who are lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; QD orally
EXPERIMENTAL: SPD476 (1.2 g)	Drug: SPD476 (1.2g); 1.2g SPD476 once daily (QD) orally; Other Names: Lialda, MMX™ mesalazine
EXPERIMENTAL: SPD476 (2.4 g)	Drug: SPD476 (2.4 g); 2.4g SPD476 QD orally; Other Names: Lialda, MMX™ mesalazine
EXPERIMENTAL: SPD476 (4.8 g)	Drug: SPD476 (4.8 g); 4.8g SPD476 QD orally; Other Names: Lialda, MMX™ mesalazine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Without Recurrence of Diverticulitis	Recurrence of diverticulitis is defined as the presence of each and all of the following 3 items: 1) abdominal pain, 2) a 15% increase in white blood cell count from baseline, 3) bowel wall thickening (>5 mm) and/or fat stranding as evidenced by spiral computerized axial tomography (CT) scan; OR surgical intervention for diverticular disease. Withdrawals are considered as recurrences.	Up to 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Who Were CT-Recurrence Free of Diverticulitis	CT-recurrence of diverticulitis is defined as: a positive spiral CT scan for diverticulitis showing, at a minimum, fat stranding with or without bowel wall thickening >5 mm or surgical intervention for diverticular disease. Withdrawals considered as CT-recurrences.	Up to 104 weeks
Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Positive	A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.	Up to 104 weeks
Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Negative	A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.	Up to 104 weeks
Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Positive	A positive CT scan was defined as a CT scan that showed bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.	Up to 104 weeks
Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Negative	A negative CT scan was defined as a CT scan that did not show bowel wall thickening (>5 mm) and/or fat stranding as read by the central reader.	Up to 104 weeks
Percent of Subjects Requiring Surgery for Diverticulitis		Up to 104 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Raskin JB, Kamm MA, Jamal MM, Marquez J, Melzer E, Schoen RE, Szaloki T, Barrett K, Streck P. Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials. Gastroenterology. 2014 Oct;147(4):793-802. doi: 10.1053/j.gastro.2014.07.004. Epub 2014 Jul 16.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 28, 2007
• Primary Completion (ACTUAL): March 5, 2012
• Study Completion (ACTUAL): March 5, 2012

Study Registration Dates

• First Submitted: October 16, 2007
• First Submitted That Met QC Criteria: October 16, 2007
• First Posted (ESTIMATE): October 17, 2007

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Diverticular Diseases; Recurrence; Diverticulitis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: SPD476-313; 2007-004895-37 (EUDRACT_NUMBER)