Prevention of Recurrence of Diverticulitis (PREVENT1)

• ClinicalTrials.gov Identifier: NCT00545740
• Recruitment Status: Completed
• First Posted: October 17, 2007
• Results First Posted: January 25, 2013
• Last Update Posted: June 14, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Tracking Information

• First Submitted Date: October 16, 2007
• First Posted Date: October 17, 2007
• Results First Submitted Date: December 19, 2012
• Results First Posted Date: January 25, 2013
• Last Update Posted Date: June 14, 2021
• Actual Study Start Date: November 28, 2007
• Actual Primary Completion Date: March 5, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2013)

Percent of Subjects Without Recurrence of Diverticulitis [ Time Frame: Up to 104 weeks ]

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.

Original Primary Outcome Measures (submitted: October 16, 2007)

• Changes in predefined lab parameters [ Time Frame: 104 Weeks ]
• Time to presence of predefined symptoms of diverticulitis [ Time Frame: 104 Weeks ]

Current Secondary Outcome Measures (submitted: December 19, 2012)

• Percent of Subjects Who Were CT-Recurrence Free of Diverticulitis [ Time Frame: Up to 104 weeks ]
  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.
• Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Positive [ Time Frame: Up to 104 weeks ]
  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.
• Number of CT Scans Performed Within 7 Days of Suspected Recurrence of Diverticulitis That Were Negative [ Time Frame: Up to 104 weeks ]
  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.
• Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Positive [ Time Frame: Up to 104 weeks ]
  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.
• Number of CT Scans Performed More Than 7 Days From Suspected Recurrence of Diverticulitis That Were Negative [ Time Frame: Up to 104 weeks ]
  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.
• Percent of Subjects Requiring Surgery for Diverticulitis [ Time Frame: Up to 104 weeks ]

Original Secondary Outcome Measures (submitted: October 16, 2007)

• Proportion of subjects without recurrence of diverticulitis between 3 doses of SPD476 and placebo [ Time Frame: 26 and 52 Weeks ]
• Evaluate the subgroup classifications of diverticulitis between 3 doses of SPD476 and placebo [ Time Frame: 104 Weeks ]
• Proportion of subjects requiring surgical intervention for diverticular disease up to 104 weeks post baseline between 3 doses of SPD476 and placebo QD [ Time Frame: 104 Weeks ]
• Quality of Life (QoL)questionnaires between treatment groups [ Time Frame: Baseline, 16, 52 and 104 Weeks ]
• To assess the safety and tolerability of SPD476 at 3 different doses [ Time Frame: 104 Weeks ]
• Flexible sigmoidoscopy assessments between treatment groups [ Time Frame: 104 Weeks ]
• Histology of biopsy samples between treatment groups [ Time Frame: 104 Weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prevention of Recurrence of Diverticulitis
• Official Title: 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.
• Brief Summary: The purpose of this study is to determine whether SPD476 is effective in reducing recurrence of diverticulitis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Diverticulitis

Intervention

• Drug: SPD476 (1.2g)
  1.2g SPD476 once daily (QD) orally
  Other Name: Lialda, MMX™ mesalazine
• Drug: SPD476 (2.4 g)
  2.4g SPD476 QD orally
  Other Name: Lialda, MMX™ mesalazine
• Drug: SPD476 (4.8 g)
  4.8g SPD476 QD orally
  Other Name: Lialda, MMX™ mesalazine
• Drug: Placebo
  QD orally

Study Arms

• Experimental: SPD476 (1.2 g)
  Intervention: Drug: SPD476 (1.2g)
• Experimental: SPD476 (2.4 g)
  Intervention: Drug: SPD476 (2.4 g)
• Experimental: SPD476 (4.8 g)
  Intervention: Drug: SPD476 (4.8 g)
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Raskin JB, Kamm MA, Jamal MM, Márquez J, Melzer E, Schoen RE, Szalóki 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 8, 2012): 590
• Original Estimated Enrollment (submitted: October 16, 2007): 584
• Actual Study Completion Date: March 5, 2012
• Actual Primary Completion Date: March 5, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Colombia, France, India, Israel, New Zealand, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT00545740
• Other Study ID Numbers: SPD476-313; 2007-004895-37 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Takeda ( Shire )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Shire
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Takeda

• PRS Account: Takeda
• Verification Date: June 2021