Rifaximin and Misoprostol Combination Therapy for Healing of Small Bowel Ulcers in Aspirin Users

NCT ID: NCT03962283

Last Updated: 2020-07-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-02
• Study Completion Date: 2023-06-30

Brief 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. 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.

Conditions

Small Bowel Disease; Rifaximin

Study Design

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

Study Groups

Rifaximin

ASA daily + misoprostol + Rifaximin (Rifaximin group)

Group Type: ACTIVE_COMPARATOR

Rifaximin

Intervention Type: DRUG

Rifaximin 200mcg four times daily

Rifaximin Placebo

ASA daily + misoprostol + Placebo Rifaximin (Placebo group)

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Placebo Rifaximin four times daily

Interventions

Rifaximin

Rifaximin 200mcg four times daily

Intervention Type: DRUG

Placebo oral tablet

Placebo Rifaximin four times daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

Beijing Friendship Hospital

OTHER

Sponsor Role: collaborator

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Francis KL Chan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francis Chan, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

China; Hong Kong

Central Contacts

Jessica CHING, MPH

Role: CONTACT

jessicaching@cuhk.edu.hk

+852 3505 3524

Pui Kuan Cheong, MPH

Role: CONTACT

jcheong@cuhk.edu.hk

+852 3505 3476

Facility Contacts

Rui Cheng, MD

Role: primary

15901103303@163.com

86-15901103303

Pui Kuan Cheong, MPH

Role: primary

jcheong@cuhk.edu.hk

852-35053476

Other Identifiers

MISO RF

Identifier Type: -

Identifier Source: org_study_id