Ulcer HemorrhagePhase 2/3NCT01998776
Evaluate Misoprostol for the Healing of Small Bowel Ulcers in Low-dose Aspirin Users Complicated by Small Bowel Bleeding
A Phase 2/3 study testing Misoprostol in people with Ulcer Hemorrhage, run by Chinese University of Hong Kong at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcer Hemorrhage
- What is being tested?
- Misoprostol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Apr 2013to Feb 2018
- 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 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Japan1 site
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Osaka, 545-8585
About this study
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)
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.
Read the 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.
- Conditions
- Ulcer Hemorrhage
- Being tested
- Misoprostol, Placebo
- Keywords
- ulcer
- Medical subject headings
- Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MisoprostolDrug
Also called Cytotec
Misoprostol 200ug four times daily
PlaceboDrug
Also called Placebo Starch
Placebo Starch four times daily
| Study group | Role | What they receive |
|---|---|---|
| Misoprostol | Active comparator | ASA 100 mg daily + misoprostol 200 four times daily (misoprostol group) Receives: Drug: Misoprostol |
| Placebo misoprostol | Placebo comparator | ASA 100 mg daily + placebo misoprostol four times daily (placebo group) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete healing of small bowel ulcers
The primary outcome is complete healing of small bowel ulcers in 8 weeks
Measured: 8 weeks
Secondary outcomes (1)
Change in numbers of ulcer/erosions, and hemoglobin level
Secondary outcomes include change in the numbers of ulcer/erosions and change in blood hemoglobin level from baseline
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2013 (estimated)
- Study startApr 2013
- Primary completion22 Jan 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcer HemorrhageStudies 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francis KL Chan, Chinese University of Hong Kong
- Investigators
- Francis KL Chan, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01998776
- Sponsor's protocol ID
- MISO-SB
- Status last verified
- Jan 2019
- First submitted
- 25 Nov 2013
- Last updated
- 31 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29966612
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01998776
- Acronym / sponsor ID
- MISO-SB
- Conditions
- Ulcer Hemorrhage
- Keywords
- ulcer
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- 22 Jan 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 2 Dec 2013 (estimated)
- 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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Misoprostol | Active comparator | Drug: MisoprostolASA 100 mg daily + misoprostol 200 four times daily (misoprostol group) |
| Placebo misoprostol | Placebo comparator | Drug: PlaceboASA 100 mg daily + placebo misoprostol four times daily (placebo group) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| MisoprostolAlso: CytotecMisoprostol 200ug four times daily | Drug | Misoprostol |
| PlaceboAlso: Placebo StarchPlacebo Starch four times daily | Drug | Placebo misoprostol |
Primary outcome
Complete healing of small bowel ulcers
Time frame: 8 weeks
The primary outcome is complete healing of small bowel ulcers in 8 weeks
1 secondary outcome
Change in numbers of ulcer/erosions, and hemoglobin level
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2019.
- Derived from this study: PubMed 29966612Kyaw 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.
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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 KL 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 Misoprostol in people with Ulcer Hemorrhage, 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 5 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: finished, as of the sponsor's last update on 31 Jan 2019. 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, Japan. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete healing of small bowel ulcers (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01998776, which also lists 1 linked publication.
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 31 Jan 2019.