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

NCT ID: NCT03537157

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-16
• Study Completion Date: 2020-07-29

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.

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.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Rifaximin delayed release tablets

Two 400 mg tablets twice a day (total daily dose 1600 mg) for 26 weeks

Group Type: EXPERIMENTAL

Rifaximin delayed release tablets

Intervention Type: DRUG

Active intervention

Placebo

Two placebo tablets twice a day for 26 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Comparator placebo

Interventions

Rifaximin delayed release tablets

Active intervention

Intervention Type: DRUG

Placebo

Comparator placebo

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cromsource

INDUSTRY

Sponsor Role: collaborator

Alfasigma S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Grimaldi, MD

Role: STUDY_DIRECTOR

Alfasigma S.p.A.

Locations

Humanitas Clinical Research Center

Rozzano, , Italy

Countries

Italy

Other Identifiers

RETIPC/01/17

Identifier Type: -

Identifier Source: org_study_id