Evaluate Misoprostol for the Healing of Small Bowel Ulcers in Low-dose Aspirin Users Complicated by Small Bowel Bleeding

Phase 2

Completed

• Conditions: Ulcer Hemorrhage
• Interventions: Drug: Placebo; Drug: Misoprostol

• Registration Number: NCT01998776
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

ASA is the most commonly drug used worldwide for prevention of cardiovascular diseases. However, ASA is increasingly recognized as a culprit for small bowel bleeding. Small bowel bleeding is notoriously difficult to diagnose because it is beyond the reach of conventional endoscopy. The advent of wireless, video capsule endoscopy has revolutionized the visualization of small bowel. Capsule endoscopy is a pill that contains a tiny camera for capturing pictures of the small bowel after being swallowed. Currently, capsule endoscopy is a recommended noninvasive approach of identifying the source of small bowel bleeding.

Management of ASA-associated small bowel bleeding is a major clinical challenge since there is not a single effective treatment for small bowel ulcer, and continuation of ASA increases the risk of recurrent small bowel bleeding. However, discontinuation of ASA exposes patients to thrombotic complications. Suppression of prostaglandin synthesis is an important mechanism of ASA-induced small injury. Consistent with this theory, preliminary data from a case series showed that misoprostol, a prostaglandin analog, healed small bowel ulcers in ASA users. However, the efficacy of misoprostol in healing ASA-associated small bowel ulcers has not yet been confirmed by prospective randomized trials.

This double-blind clinical trial tests the hypothesis that misoprostol can heal small bowel ulcers in Aspirin users complicated by small bowel bleeding.

Detailed Description

ASA is the most commonly drug used worldwide for prevention of cardiovascular diseases. However, ASA is increasingly recognized as a culprit for small bowel bleeding. The latter condition manifests as overt bleeding (i.e., passing black or bright red stool) or occult blood loss (i.e., normal stool but progressive decrease in hemoglobin level), with normal findings in the stomach and colon. Small bowel bleeding is notoriously difficult to diagnose because it is beyond the reach of conventional endoscopy. The advent of wireless, video capsule endoscopy has revolutionized the visualization of small bowel. Capsule endoscopy is a pill that contains a tiny camera for capturing pictures of the small bowel after being swallowed. Currently, capsule endoscopy is a recommended noninvasive approach of identifying the source of small bowel bleeding.

The problem of small bowel bleeding is increasingly recognized, partly because the use of ASA is rising. In a regional hospital in Hong Kong, we diagnose about 100 cases of ASA-associated small bowel overt bleeding/occult blood loss each year. In a prospective cohort study we found that among ASA users with a history of small bowel bleeding, the risk of recurrent small bowel bleeding is 4 times higher in patients who continued to use ASA than in those who discontinued ASA.

Management of ASA-associated small bowel bleeding is a major clinical challenge for two reasons. First, there is not a single effective treatment for small bowel ulcer. Unlike peptic ulcers, injury to the small bowel is acid-independent. Thus, conventional stomach protective drugs cannot heal or prevent small bowel ulcers in ASA users. Neither can switching to other non-ASA anti-platelet drugs reduce the risk of bleeding. Second, we have shown that continuation of ASA increases the risk of recurrent small bowel bleeding. However, discontinuation of ASA exposes patients to thrombotic complications. Currently, there is no local or international guideline on the management of ASA-associated small bowel bleeding.

Suppression of prostaglandin synthesis is an important mechanism of ASA-induced small injury. Consistent with this theory, preliminary data from a case series showed that misoprostol, a prostaglandin analog, healed small bowel ulcers in ASA users. However, the efficacy of misoprostol in healing ASA-associated small bowel ulcers has not yet been confirmed by prospective randomized trials.

Study Timeline

• Study Start: 2013-04
• Study First Submitted: 2013-11-25
• Study First Submitted QC: 2013-11-29
• Study First Posted: 2013-12-02
• Primary Completion: 2018-01-22
• Study Completion: 2018-02
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-29
• Last Update Posted: 2019-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo misoprostol	Placebo	ASA 100 mg daily + placebo misoprostol four times daily (placebo group)
Misoprostol	Misoprostol	ASA 100 mg daily + misoprostol 200 four times daily (misoprostol group)

Primary Outcome Measures

Name	Time	Method
Complete healing of small bowel ulcers	8 weeks	The primary outcome is complete healing of small bowel ulcers in 8 weeks

Secondary Outcome Measures

Name	Time	Method
Change in numbers of ulcer/erosions, and hemoglobin level	8 weeks	Secondary outcomes include change in the numbers of ulcer/erosions and change in blood hemoglobin level from baseline

Trial Locations

Locations (2)

Department of Gastroenterology, Osaka City University Graduate School of Medicine; 🇯🇵 Osaka, Japan

Prince of Wales Hospital; 🇨🇳 Hong Kong, China