Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Multicentre Study on Rifaximin in Post-operative Endoscopic Crohn's Disease Recurrence Prevention (STOP-PER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03537157
Recruitment Status : Terminated (The decision to prematurely close the trial recruitment period was taken due to the difficulties in the recruitment of patients. This decision has not been triggered by any unexpected safety signals identified during the study conduction.)
First Posted : May 25, 2018
Last Update Posted : September 27, 2021
Sponsor:
Collaborator:
Cromsource
Information provided by (Responsible Party):
Alfasigma S.p.A.

Brief Summary:
Crohn's Disease (CD) is a chronic pathology characterized by exacerbations and remissions. Recurrent inflammation can cause bowel strictures, fistulae (often perianal) or abscesses. CD often requires intestinal resection. Surgery in CD is not curative, Therefore, endoscopic follow-up 6-12 months after surgery is recommended. Given the association between enteric bacteria and postoperative CD recurrence, antibacterial agents were shown to be effective in reducing the severity of endoscopic recurrence, but prolonged administration causes significant toxicity. The efficacy of "systemic antibiotics" and the experimental evidence of the central role of luminal flora as an essential factor in the development of post chirurgic CD recurrence provide the rationale for evaluating a locally acting antibiotic like Rifaximin.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Rifaximin delayed release tablets Other: Placebo Phase 2

Detailed Description:

Crohn's disease (CD) is a chronic, relapsing, remitting, systemic disease, which may result in transmural inflammation of the gastrointestinal tract. The precise aetiology is unknown: it is a lifelong disease arising from an interaction between genetic and environmental factors, but predominantly observed in developed countries of the world. CD can affect the entire digestive tract from the mouth to the anus, but the most commonly affected sites are the ileum and the ascending colon . The clinical course of CD is characterized by exacerbations and remissions. Therefore, recurrent inflammation can cause bowel strictures, fistulae (often perianal) or abscesses. Moreover, Crohn's disease (CD) often requires intestinal resection, despite treatment with immunosuppressive and biologic therapies.

Surgery in CD is not curative, and post-operative recurrence (POR) is a frequent event. Historically, up to 70% of patients who undergo CD-related resection develop postoperative endoscopic recurrence at or proximal to the surgical anastomosis within 1 year and approximately one-third of patients with CD, who have a first resection, require a second within 10 years.

Endoscopic lesions usually precede and correlate with future clinical recurrence (about 20-25% per year), and predict the development of Crohn's disease-related complications and the need for re-intervention.

Therefore, endoscopic follow-up 6-12 months after surgery is recommended. Given the association between enteric bacteria and postoperative CD recurrence, antibacterial agents directed against anaerobic bacteria (ornidazole and metronidazole) were shown to be effective in reducing the severity of endoscopic recurrence, but prolonged administration (more than 3 months) of these antibiotics causes significant toxicity, mainly neuropathy and gastrointestinal intolerance. The efficacy of "systemic antibiotics" and the experimental evidence of the central role of luminal flora as an essential factor in the development of post chirurgic CD recurrence provide the rationale for evaluating a locally acting antibiotic like Rifaximin in this condition.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study is a multicentre, randomised, double-blind, placebo controlled trial to assess the efficacy and safety of Rifaximin delayed release 400 mg tablet (800 mg BID daily) administered for 26 weeks in the prevention of endoscopic Crohn's disease recurrence following ileocolonic resection, in patients who had undergone curative ileocolonic resection, with ileocolonic anastomosis for Crohn's disease.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Active drug will be masked with a placebo identical to the active drug. Patients will be identified by a code and central readers will not have access to the administered treatments
Primary Purpose: Prevention
Official Title: A Phase II, Multicentre, Double-blind, Randomised, Placebo-controlled Study of Rifaximin Delayed Release 400 mg Tablet: Clinical Efficacy and Safety in the Prevention of Post-operative Endoscopic Crohn's Disease Recurrence
Actual Study Start Date : November 16, 2017
Actual Primary Completion Date : July 15, 2020
Actual Study Completion Date : July 29, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rifaximin

Arm Intervention/treatment
Experimental: Rifaximin delayed release tablets
Two 400 mg tablets twice a day (total daily dose 1600 mg) for 26 weeks
Drug: Rifaximin delayed release tablets
Active intervention

Placebo Comparator: Placebo
Two placebo tablets twice a day for 26 weeks
Other: Placebo
Comparator placebo




Primary Outcome Measures :
  1. Rutgeerts score [ Time Frame: 26 weeks ]
    Rate of patients presenting a rutgeerts score higher than or equal to i2 will be considered as endpoint. Endoscopic remission will be defined as a Rutgeerts score of i0 or i1 and recurrence defined as a Rutgeerts score of ≥i2 (i0, no lesions; i1, ≤5 aphthous lesions; i2, >5 aphthous lesions or anastomotic ulcer <1 cm; i3, diffuse aphthous ileitis with diffusely inflamed mucosa; i4, diffuse inflammation with large ulcers, nodules, and/or narrowing) at the anastomosis and neoterminal ileum. (Rutgeerts P, 1990)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Crohn Disease with curative ileocolonic resection
  • Randomization within 45 days from ileocolonic resection or end or loop ileostomy within last year and closure occurred within 45 days from randomization
  • Fecal stream restoration at least 14 days prior to randomization
  • Presence of at least one risk factor for recurrence
  • Pregnancy protection on board during the study for childbearing female subjects

Exclusion Criteria:

  • Presence of CD proximally or distally to the site of resection
  • Patients with strictureplasties at index surgery or ileorectal anastomosis
  • patients with active perianal CD
  • Patient treated with other treatments usually utilised for CD
  • Patients with active diseases with gastrointestinal involvement
  • intestinal obstruction or pseudo-obstruction
  • Patients presenting diarrhoea plus fever or bloody stools
  • Positivity to clostridium difficile toxin
  • Severe hepatic or renal impairment
  • Presence of severe cardiac insufficiency
  • Hypersensitivity to rifamycin antimicrobial agents
  • other conditions that would interfere or prevent the study completion
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03537157


Locations
Layout table for location information
Italy
Humanitas Clinical Research Center
Rozzano, Italy, 20089
Sponsors and Collaborators
Alfasigma S.p.A.
Cromsource
Investigators
Layout table for investigator information
Study Director: Maria Grimaldi, MD Alfasigma S.p.A.
Layout table for additonal information
Responsible Party: Alfasigma S.p.A.
ClinicalTrials.gov Identifier: NCT03537157    
Other Study ID Numbers: RETIPC/01/17
First Posted: May 25, 2018    Key Record Dates
Last Update Posted: September 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alfasigma S.p.A.:
Crohn Disease recurrence
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Recurrence
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes
Rifaximin
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents