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

NCT01998776 | Completed Phase 2

• 1 other identifier: MISO-SB
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 2

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.

Conditions

Ulcer Hemorrhage

Keywords

ulcer

Outcome Measures

Primary Outcomes (1)

• Complete healing of small bowel ulcers

  The primary outcome is complete healing of small bowel ulcers in 8 weeks

  8 weeks

Secondary Outcomes (1)

• Change in numbers of ulcer/erosions, and hemoglobin level

  8 weeks

Study Arms (2)

Misoprostol

ACTIVE COMPARATOR

ASA 100 mg daily + misoprostol 200 four times daily (misoprostol group)

Drug: Misoprostol

Placebo misoprostol

PLACEBO COMPARATOR

ASA 100 mg daily + placebo misoprostol four times daily (placebo group)

Drug: Placebo

Interventions

Misoprostol DRUG

Misoprostol 200ug four times daily

Also known as: Cytotec

Misoprostol

Placebo DRUG

Placebo Starch four times daily

Also known as: Placebo Starch

Placebo misoprostol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Suspected small bowel overt bleeding - melena or hematochezia with normal upper endoscopy and colonoscopy
• Suspected small bowel occult blood loss - defined as a significant decrease in hemoglobin (≥ 2g/dL), with normal upper endoscopy 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 ASA for the duration of the trial
• Age ≥ 18
• Written informed consent obtained

You may not qualify if:

• Patients are excluded if they have one or more of the following conditions
• Increased risk of capsule retention (e.g. Gastric outlet obstruction, bypass surgery, Crohn's disease or suspected small bowel stricture)
• Abnormal findings on upper endoscopy (e.g. Esophageal varices, grade C or D erosive esophagitis, vascular malformations, ulcer, ≥5 erosions, neoplasms) or colonoscopy (e.g. cancer, polyps \> 1cm, inflammatory bowel disease, vascular malformations, bleeding hemorrhoids or diverticular disease)
• Unable to swallow the video capsule
• Terminal illness
• Concomitant use of NSAIDs, sucralfate, rebamepide, anticoagulants, corticosteroids (prednisolone \> 7.5mg daily or equivalent), and iron supplement
• Pregnancy or women of child-bearing age without regular use of contraception

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

Prince of Wales Hospital

Hong Kong, China

Location

Department of Gastroenterology, Osaka City University Graduate School of Medicine

Osaka, 545-8585, Japan

Location

Related Publications (1)

• Kyaw MH, Otani K, Ching JYL, Higashimori A, Kee KM, Watanabe T, Tse YK, Lee V, Tanigawa T, Cheong PK, Suen BY, Fujiwara Y, Lam K, Arakawa T, Chan FKL. Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding. Gastroenterology. 2018 Oct;155(4):1090-1097.e1. doi: 10.1053/j.gastro.2018.06.056. Epub 2018 Sep 5.

  PMID: 29966612 DERIVED

MeSH Terms

Conditions

Ulcer

Interventions

Misoprostol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Francis KL Chan, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 2, 2013
• Study Start: April 1, 2013
• Primary Completion: January 22, 2018
• Study Completion: February 1, 2018
• Last Updated: January 31, 2019

Record last verified: 2019-01

Locations

JP (1); CN (1)