Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs

Atrial Fibrillation Clinical Trial

— 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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02202967
• Other study ID #: GN09CA403
• Secondary ID: 2013-003187-31
• Status: Completed
• Phase: Phase 3
• Start date: January 7, 2016
• Est. completion date: October 11, 2017

Study information

• Verified date: August 2018
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: October 11, 2017
• Est. primary completion date: October 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Atrial Fibrillation
• Bleeding
• Chronic Arthritis
• Coronary Artery Disease
• Heart Diseases
• Hemorrhage
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Drug:
• Misoprostol
Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog
• Placebo
Placebo contains lactose granules

Locations

Country	Name	City	State
United Kingdom	University Hospital Crosshouse	Kilmarnock	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. Lanc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in blood haemoglobin level	Any rise or drop in the haemoglobin level will be measured at the end of the study	8 weeks
Primary	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	8 weeks
Secondary	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	8 weeks

External Links

•   Taha AS et al. MASTERS Trial.Lancet Gastroenterol Hepatol 2018;3:469-76