Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs (MASTERS)
Primary Purpose
Chronic Arthritis, Ischemic Heart Disease, Atrial Fibrillation
Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Misoprostol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Arthritis focused on measuring Aspirin, Intestinal bleeding, Misoprostol, NSAIDs, Small intestine, Video capsule endoscopy
Eligibility Criteria
INCLUSION CRITERIA:
Obscure occult gastrointestinal bleeding: presence of one or more of the following:
- Positive fecal occult blood test within last 3 months
- Iron deficiency anemia (ferritin <100 ug/l, hemoglobin [Hb] 7-12 g/dl [female] or 7-13 g/dl [male])
- Drop in haemoglobin, > 2gm/dl from baseline, in the absence of potential or actively bleeding lesion detectable on upper endoscopy or colonoscopy.
Normal/ absence of potentially bleeding lesions on full upper endoscopy and colonoscopy.
Taking low-dose aspirin (75-325m/ day) and/ or NSAIDs
MAIN EXCLUSION CRITERIA:
- Incomplete upper endoscopy or colonoscopy
- Systemic disease that is unstable at the time of randomisation (unstable vital signs; ongoing non-gastrointestinal investigations; frequent modifications to treatment)
- Intake of certain drugs: high-dose steroids (>7.5-mg prednisolone/ day), cytotoxic drugs, or warfarin.
- Upper gastrointestinal lesions: oesophageal varices; oesophageal stricture; oesophageal or gastric neoplasms; pyloric stenosis; peptic ulcers; vascular malformations.
- Colonic disorders: neoplasms or adenomatous polyps; inflammatory bowel disease; vascular malformations; actively bleeding diverticular disease
- Women planning pregnancy, pregnant or women of child-bearing potential not using two contraceptive methods, one of which must be highly effective [implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner]
- Hypotension: systolic blood pressure <100-mm Hg.
Sites / Locations
- University Hospital Crosshouse
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Misoprostol
Placebo
Arm Description
Misoprostol
Placebo
Outcomes
Primary Outcome Measures
Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs.
Ulcers or smaller lesions (erosions) should totally disappear by the end of the study
Secondary Outcome Measures
Change in the numbers of mucosal ulcers and erosions
Any increase or decrease in the numbers of ulcers and erosions will be measured at the end of the study
Full Information
NCT ID
NCT02202967
First Posted
July 26, 2014
Last Updated
August 12, 2018
Sponsor
NHS Greater Glasgow and Clyde
1. Study Identification
Unique Protocol Identification Number
NCT02202967
Brief Title
Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs
Acronym
MASTERS
Official Title
Misoprostol for the Healing of Small Bowel Ulceration in Patients With Obscure Blood Loss While Taking Low-dose Aspirin or Nonsteroidal Antiinflammatory Drugs [MASTERS Trial]
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
January 7, 2016 (Actual)
Primary Completion Date
October 11, 2017 (Actual)
Study Completion Date
October 11, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NHS Greater Glasgow and Clyde
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Anti-inflammatory tablets (non-steroidal anti-inflammatory drugs) continue to be used commonly worldwide to relieve pain caused by arthritis. Likewise, aspirin is used by many patients in order to prevent blood clots. Despite their desired benefits, these medicines can cause internal bleeding from the digestive system. The source of this bleeding can be obvious (overt), or obscure and thought to come from the small intestine. Obscure bleeding can show as anemia due to lack of iron in the blood. Small intestine ulcers are now easily diagnosed using an endoscope the size of a big pill (video capsule endoscopy). Small bowel ulcers are not related to stomach acid and therefore do not heal using remedies usually taken to stop acid formation. A different drug, misoprostol, consists of a chemical (prostaglandin) that is usually lacking in patients using aspirin or anti-inflammatory drugs. Misoprostol is licenced to heal stomach and duodenal ulcers in patients using these drugs. Our hypothesis is that misoprostol might be effective in healing small bowel ulcers as suggested by pilot studies; however, such works only included small numbers of patients, did not include control groups and both patients and investigators knew the nature of the tablets used. To test this hypothesis, we propose to compare misoprostol to a dummy tablet. The numbers of subjects to be studied have been calculated using established statistical methods
Detailed Description
METHODOLOGY:
Upper gastrointestinal endoscopy and colonoscopy on patients with obscure bleeding and/ or iron deficiency anemia.
Video capsule endoscopy on those fulfilling the inclusion criteria
Randomization to Misoprostol 200 micrograms or placebo, 4 times each day given for 8 weeks to aspirin/ NSAID users with erosive small bowel lesions.
Video capsule endoscopy at 8 weeks to check healing of small bowel lesions.
Full blood count at baseline and monthly intervals (0, 4, and 8 weeks)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Arthritis, Ischemic Heart Disease, Atrial Fibrillation, Anemia, Bleeding
Keywords
Aspirin, Intestinal bleeding, Misoprostol, NSAIDs, Small intestine, Video capsule endoscopy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
104 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Misoprostol
Arm Type
Active Comparator
Arm Description
Misoprostol
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Misoprostol
Other Intervention Name(s)
Cytotec (R)
Intervention Description
Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Dummy drug
Intervention Description
Placebo contains lactose granules
Primary Outcome Measure Information:
Title
Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs.
Description
Ulcers or smaller lesions (erosions) should totally disappear by the end of the study
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Change in the numbers of mucosal ulcers and erosions
Description
Any increase or decrease in the numbers of ulcers and erosions will be measured at the end of the study
Time Frame
8 weeks
Other Pre-specified Outcome Measures:
Title
Change in blood haemoglobin level
Description
Any rise or drop in the haemoglobin level will be measured at the end of the study
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
Obscure occult gastrointestinal bleeding: presence of one or more of the following:
Positive fecal occult blood test within last 3 months
Iron deficiency anemia (ferritin <100 ug/l, hemoglobin [Hb] 7-12 g/dl [female] or 7-13 g/dl [male])
Drop in haemoglobin, > 2gm/dl from baseline, in the absence of potential or actively bleeding lesion detectable on upper endoscopy or colonoscopy.
Normal/ absence of potentially bleeding lesions on full upper endoscopy and colonoscopy.
Taking low-dose aspirin (75-325m/ day) and/ or NSAIDs
MAIN EXCLUSION CRITERIA:
Incomplete upper endoscopy or colonoscopy
Systemic disease that is unstable at the time of randomisation (unstable vital signs; ongoing non-gastrointestinal investigations; frequent modifications to treatment)
Intake of certain drugs: high-dose steroids (>7.5-mg prednisolone/ day), cytotoxic drugs, or warfarin.
Upper gastrointestinal lesions: oesophageal varices; oesophageal stricture; oesophageal or gastric neoplasms; pyloric stenosis; peptic ulcers; vascular malformations.
Colonic disorders: neoplasms or adenomatous polyps; inflammatory bowel disease; vascular malformations; actively bleeding diverticular disease
Women planning pregnancy, pregnant or women of child-bearing potential not using two contraceptive methods, one of which must be highly effective [implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner]
Hypotension: systolic blood pressure <100-mm Hg.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maureen Travers, PhD
Organizational Affiliation
NHS Greater Glasgow & Clyde, Scotland
Official's Role
Study Director
Facility Information:
Facility Name
University Hospital Crosshouse
City
Kilmarnock
State/Province
Scotland
ZIP/Postal Code
KA2 0BE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29754836
Citation
Taha AS, McCloskey C, McSkimming P, McConnachie A. Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):469-476. doi: 10.1016/S2468-1253(18)30119-5. Epub 2018 May 10.
Results Reference
result
Links:
URL
http://dx.doi.org/10.1016/S2468-1253(18)30119-5
Description
Taha AS et al. MASTERS Trial.Lancet Gastroenterol Hepatol 2018;3:469-76
Learn more about this trial
Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs
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