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

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ClinicalTrials.gov Identifier: NCT01998776
Recruitment Status : Completed
First Posted : December 2, 2013
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, 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.


Condition or disease Intervention/treatment Phase
Ulcer Hemorrhage Drug: Misoprostol Drug: Placebo Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: A Double-blind, Randomized, Placebo Controlled Trial of Misoprostol for Healing of Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding (MISO-SB Study)
Study Start Date : April 2013
Actual Primary Completion Date : January 22, 2018
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Active Comparator: Misoprostol
ASA 100 mg daily + misoprostol 200 four times daily (misoprostol group)
Drug: Misoprostol
Misoprostol 200ug four times daily
Other Name: Cytotec

Placebo Comparator: Placebo misoprostol
ASA 100 mg daily + placebo misoprostol four times daily (placebo group)
Drug: Placebo
Placebo Starch four times daily
Other Name: Placebo Starch




Primary Outcome Measures :
  1. Complete healing of small bowel ulcers [ Time Frame: 8 weeks ]
    The primary outcome is complete healing of small bowel ulcers in 8 weeks


Secondary Outcome Measures :
  1. Change in numbers of ulcer/erosions, and hemoglobin level [ Time Frame: 8 weeks ]
    Secondary outcomes include change in the numbers of ulcer/erosions and change in blood hemoglobin level from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Suspected small bowel overt bleeding - melena or hematochezia with normal upper endoscopy and colonoscopy
  2. 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)
  3. Continuous use of ASA for the duration of the trial
  4. Age ≥ 18
  5. Written informed consent obtained

Exclusion criteria:

Patients are excluded if they have one or more of the following conditions

  1. Increased risk of capsule retention (e.g. Gastric outlet obstruction, bypass surgery, Crohn's disease or suspected small bowel stricture)
  2. 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)
  3. Unable to swallow the video capsule
  4. Terminal illness
  5. Concomitant use of NSAIDs, sucralfate, rebamepide, anticoagulants, corticosteroids (prednisolone > 7.5mg daily or equivalent), and iron supplement
  6. Pregnancy or women of child-bearing age without regular use of contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01998776


Locations
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China
Prince of Wales Hospital
Hong Kong, China
Japan
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Osaka, Japan, 545-8585
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
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Principal Investigator: Francis KL Chan, MD Chinese University of Hong Kong

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Francis KL Chan, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01998776     History of Changes
Other Study ID Numbers: MISO-SB
First Posted: December 2, 2013    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Keywords provided by Francis KL Chan, Chinese University of Hong Kong:
ulcer
Additional relevant MeSH terms:
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Aspirin
Ulcer
Hemorrhage
Pathologic Processes
Misoprostol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Oxytocics