Crohn DiseasePhase 2STOP-PERNCT03537157
A Multicentre Study on Rifaximin in Post-operative Endoscopic Crohn's Disease Recurrence Prevention
A Phase 2 study testing Rifaximin delayed release tablets in people with Crohn Disease, run by Alfasigma S.p.A. at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Rifaximin delayed release tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteItaly
- Study dates
- 16 Nov 2017to 29 Jul 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Rifaximin delayed release tablets, Placebo
- Keywords
- Crohn Disease recurrence
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifaximin delayed release tabletsDrug
Active intervention
PlaceboOther
Comparator placebo
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin delayed release tablets | Experimental | Two 400 mg tablets twice a day (total daily dose 1600 mg) for 26 weeks Receives: Drug: Rifaximin delayed release tablets |
| Placebo | Placebo comparator | Two placebo tablets twice a day for 26 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rutgeerts score
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)
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start16 Nov 2017
- Primary completion15 Jul 2020
- Study completion29 Jul 2020
Why it stopped: 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alfasigma S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Responsible party
- Sponsor
- Investigators
- Maria Grimaldi, MD, Study director, Alfasigma S.p.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537157
- Sponsor's protocol ID
- RETIPC/01/17
- Acronym
- STOP-PER
- Status last verified
- Jul 2021
- First submitted
- 15 May 2018
- Last updated
- 27 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03537157
- Acronym / sponsor ID
- STOP-PER / RETIPC/01/17
- Conditions
- Crohn Disease
- Keywords
- Crohn Disease recurrence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 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.
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Alfasigma S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 15 Jul 2020 (actual)
- Study completion
- 29 Jul 2020 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Rifaximin delayed release tablets | Experimental | Drug: Rifaximin delayed release tabletsTwo 400 mg tablets twice a day (total daily dose 1600 mg) for 26 weeks |
| Placebo | Placebo comparator | Other: PlaceboTwo placebo tablets twice a day for 26 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rifaximin delayed release tabletsActive intervention | Drug | Rifaximin delayed release tablets |
| PlaceboComparator placebo | Other | Placebo |
Primary outcome
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)
Results and safety
The study was stopped early (reason given: 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.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Grimaldi, MD study director
Alfasigma S.p.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rifaximin delayed release tablets in people with Crohn Disease, run by Alfasigma S.p.A. at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rutgeerts score (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2021.