Small Bowel DiseasePhase 2/3NCT03962283
Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users
A Phase 2/3 study testing Rifaximin in people with Small Bowel Disease and Rifaximin, run by Chinese University of Hong Kong at 2 sites in 2 countries.
Trial summary
Background: Investigators have previously shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the rate of small-bowel mucosal healing was low with use of misoprostol alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Bowel Disease, Rifaximin
- What is being tested?
- Rifaximin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 2 Aug 2019to 30 Jun 2023
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Suspected small bowel overt bleeding - melena or hematochezia with or without a source of bleeding from gastroscopy and colonoscopy or suspected small bowel occult blood loss - defined as a significant decrease in hemoglobin (> 2g/dL), without a source of bleeding from gastroscopy and colonoscopy, confirmed iron deficiency anemia, and absence of other identifiable causes for hemoglobin decrease (e.g. fluid overload, progressive renal failure, malnutrition, or other hematological disorders such as hemolysis or malignancies)
- Continuous use of aspirin for the duration of the trial
- Age ≥ 18
- Written informed consent obtained
Who cannot join
- Increased risk of capsule retention (e.g. gastric outlet obstruction, bypass surgery, Crohn's disease or suspected small bowel stricture)
- Abnormal findings on gastroscopy that may account for bleeding episode: clean-based ulcer >2 cm or >5 erosions, esophageal varices, grade C or D erosive esophagitis, vascular malformations
- Unable to swallow the capsule endoscopy
- Terminal illness
- Concomitant use of NSAIDs, sucralfate, rebamepide, antibiotics, corticosteroids (prednisolone >7.5 mg daily or equivalent), and iron supplement
- Pregnancy (except LMP within 7 days) or women of child-bearing age without regular use of contraception
- Contraindications to colonoscopy or capsule endoscopy
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
China1 site, 1 recruiting
- Recruiting
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 000
Rui Cheng, MD, 86-15901103303, 15901103303@163.com
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong, 000
Pui Kuan Cheong, MPH, 852-35053476, jcheong@cuhk.edu.hk
About this study
Official title: Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding: A Double Blind Randomized Trial
Background: Investigators have previously shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the rate of small-bowel mucosal healing was low with use of misoprostol alone. There is evidence to suggest that bacteria contribute to the development aspirin-induced ulcers and antibiotics may be useful in its treatment. Rifaximin, a non-absorbed oral antibiotic that target the gastrointestinal tract have been shown to be safe and effective in a few other gastrointestinal conditions.
Small bowel capsule is the most sensitive and non-invasive way to investigate the small bowel. It plays an important role in obscure GIB investigations.
Read more
Aims: The aim of this randomized study is to test the hypothesis that misoprostol combined with rifaximin is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.
Study design: 8-week double-blind randomized trial
Read the detailed description
Aspirin is one of the most commonly prescribed drugs worldwide It is widely used as the first line agent for prevention and treatment of heart diseases and stroke. It is well recognized that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of upper gastrointestinal (the stomach) bleeding. It is increasingly recognized to have adverse effects in the small bowel, including ulcers resulting in bleeding.
Bleeding from the small bowel has been very difficult to diagnose as it is beyond the reach of the conventional endoscopy. But with advances in endoscopic technique, video capsule endoscopy is now available to visualize the whole of the digestive tract. Capsule endoscopy is the size and shape of a pill which contains a tiny camera. After ingesting the capsule, pictures are taken inside of the gastrointestinal tract. Capsule endoscopy is now recommended to be a noninvasive test to identify source of small bowel bleeding.
Investigators have recently shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the complete healing rate with misoprostol alone was only 40%. This suggests that we should continue to investigate for additional therapies in order to achieve higher success rate of healing of aspirin-induced small bowel ulcers.
Rifaximin is a non-absorbed oral antibiotic that targets the gastrointestinal tract. It was first described in 1982 and introduced into the Italian market 5 years later. Since then, rifaximin has had U.S. Food and Drug Administration (FDA) approval for treatment of travellers' diarrhea (year approved = 2004), hepatic encephalopathy (year approved=2010), irritable bowel syndrome (IBS) with diarrhea (year approved= 2015). Unlike the systematically available antibiotics, it allows localized enteric targeting of pathogens and is associated with minimal risk of systemic toxicity or side effects. In addition, the restricted use of non-absorbed oral antibiotics should also reduce the development of wide spread resistance.
The aim of this study is to test the hypothesis that the combination therapy of rifaximin and misoprostol is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.
Participants are invited to this study because some predefined lesions are detected by the small bowel capsule endoscopy. Participants will be randomly assigned to receive either a combination therapy of misoprostol and rifaximin or misoprostol and rifaximin placebo for 8 weeks. Participants will be contacted by telephone after 1 week for any adverse events. Participants will then return at Week 8 to undergo a follow-up capsule endoscopy. Lab tests, drug compliance, and adverse events will be assessed.
- Conditions
- Small Bowel Disease, Rifaximin
- Being tested
- Rifaximin, Placebo oral tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Rifaximin 200mcg four times daily
Placebo oral tabletDrug
Placebo Rifaximin four times daily
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin | Active comparator | ASA daily + misoprostol + Rifaximin (Rifaximin group) Receives: Drug: Rifaximin |
| Rifaximin Placebo | Placebo comparator | ASA daily + misoprostol + Placebo Rifaximin (Placebo group) Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Healing of small bowel ulcers
Capsule endoscopy will be performed to check if there is complete healing of small bowel ulcers, with or without red spots.
Measured: 8 weeks after randomization
Secondary outcomes (2)
Change in numbers of ulcer/erosions
Change in numbers of ulcer/erosions from baseline within and between groups
Measured: 8 weeks after randomization
Change in blood hemoglobin level
Change in blood hemoglobin level from baseline within and between groups
Measured: 8 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start2 Aug 2019
- Primary completion30 Jun 2022 (estimated)
- Study completion30 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Bowel DiseaseStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Friendship Hospital
- Responsible party
- Principal investigator, Francis KL Chan, Chinese University of Hong Kong
- Investigators
- Francis Chan, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962283
- Sponsor's protocol ID
- MISO RF
- Status last verified
- Jun 2020
- First submitted
- 19 May 2019
- Last updated
- 1 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding: A Double Blind Randomized Trial
- ClinicalTrials.gov ID
- NCT03962283
- Acronym / sponsor ID
- MISO RF
- Conditions
- Small Bowel Disease, Rifaximin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- Beijing Friendship Hospital
- Study start
- 2 Aug 2019 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 24 May 2019 (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.
Background: Investigators have previously shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the rate of small-bowel mucosal healing was low with use of misoprostol alone. There is evidence to suggest that bacteria contribute to the development aspirin-induced ulcers and antibiotics may be useful in its treatment. Rifaximin, a non-absorbed oral antibiotic that target the gastrointestinal tract have been shown to be safe and effective in a few other gastrointestinal conditions.
Small bowel capsule is the most sensitive and non-invasive way to investigate the small bowel. It plays an important role in obscure GIB investigations.
Aims: The aim of this randomized study is to test the hypothesis that misoprostol combined with rifaximin is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.
Study design: 8-week double-blind randomized trial
Detailed description
Aspirin is one of the most commonly prescribed drugs worldwide It is widely used as the first line agent for prevention and treatment of heart diseases and stroke. It is well recognized that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are associated with risk of upper gastrointestinal (the stomach) bleeding. It is increasingly recognized to have adverse effects in the small bowel, including ulcers resulting in bleeding.
Bleeding from the small bowel has been very difficult to diagnose as it is beyond the reach of the conventional endoscopy. But with advances in endoscopic technique, video capsule endoscopy is now available to visualize the whole of the digestive tract. Capsule endoscopy is the size and shape of a pill which contains a tiny camera. After ingesting the capsule, pictures are taken inside of the gastrointestinal tract. Capsule endoscopy is now recommended to be a noninvasive test to identify source of small bowel bleeding.
Investigators have recently shown that misoprostol can heal small bowel ulcers in aspirin users with small bowel bleeding. However, the complete healing rate with misoprostol alone was only 40%. This suggests that we should continue to investigate for additional therapies in order to achieve higher success rate of healing of aspirin-induced small bowel ulcers.
Rifaximin is a non-absorbed oral antibiotic that targets the gastrointestinal tract. It was first described in 1982 and introduced into the Italian market 5 years later. Since then, rifaximin has had U.S. Food and Drug Administration (FDA) approval for treatment of travellers' diarrhea (year approved = 2004), hepatic encephalopathy (year approved=2010), irritable bowel syndrome (IBS) with diarrhea (year approved= 2015). Unlike the systematically available antibiotics, it allows localized enteric targeting of pathogens and is associated with minimal risk of systemic toxicity or side effects. In addition, the restricted use of non-absorbed oral antibiotics should also reduce the development of wide spread resistance.
The aim of this study is to test the hypothesis that the combination therapy of rifaximin and misoprostol is superior to misoprostol alone for healing of small bowel ulcers in aspirin users complicated by small bowel bleeding.
Participants are invited to this study because some predefined lesions are detected by the small bowel capsule endoscopy. Participants will be randomly assigned to receive either a combination therapy of misoprostol and rifaximin or misoprostol and rifaximin placebo for 8 weeks. Participants will be contacted by telephone after 1 week for any adverse events. Participants will then return at Week 8 to undergo a follow-up capsule endoscopy. Lab tests, drug compliance, and adverse events will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin | Active comparator | Drug: RifaximinASA daily + misoprostol + Rifaximin (Rifaximin group) |
| Rifaximin Placebo | Placebo comparator | Drug: Placebo oral tabletASA daily + misoprostol + Placebo Rifaximin (Placebo group) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Suspected small bowel overt bleeding - melena or hematochezia with or without a source of bleeding from gastroscopy and colonoscopy or suspected small bowel occult blood loss - defined as a significant decrease in hemoglobin (> 2g/dL), without a source of bleeding from gastroscopy and colonoscopy, confirmed iron deficiency anemia, and absence of other identifiable causes for hemoglobin decrease (e.g. fluid overload, progressive renal failure, malnutrition, or other hematological disorders such as hemolysis or malignancies)
- Continuous use of aspirin for the duration of the trial
- Age ≥ 18
- Written informed consent obtained
Key exclusion criteria (7 listed)
- Increased risk of capsule retention (e.g. gastric outlet obstruction, bypass surgery, Crohn's disease or suspected small bowel stricture)
- Abnormal findings on gastroscopy that may account for bleeding episode: clean-based ulcer >2 cm or >5 erosions, esophageal varices, grade C or D erosive esophagitis, vascular malformations
- Unable to swallow the capsule endoscopy
- Terminal illness
- Concomitant use of NSAIDs, sucralfate, rebamepide, antibiotics, corticosteroids (prednisolone >7.5 mg daily or equivalent), and iron supplement
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 |
|---|---|---|
| RifaximinRifaximin 200mcg four times daily | Drug | Rifaximin |
| Placebo oral tabletPlacebo Rifaximin four times daily | Drug | Rifaximin Placebo |
Primary outcome
Healing of small bowel ulcers
Time frame: 8 weeks after randomization
Capsule endoscopy will be performed to check if there is complete healing of small bowel ulcers, with or without red spots.
2 secondary outcomes
Change in numbers of ulcer/erosions
Time frame: 8 weeks after randomization
Change in blood hemoglobin level
Time frame: 8 weeks after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
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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.
Francis Chan, MD principal investigator
Chinese University of Hong Kong
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rifaximin in people with Small Bowel Disease and Rifaximin, run by Chinese University of Hong Kong at 2 sites in 2 countries.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Hong Kong. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jessica CHING, MPH (+852 3505 3524, jessicaching@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Healing of small bowel ulcers (time frame: 8 weeks after randomization). 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 1 Jul 2020.