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

NHS Trust

Status and phase

Completed

Phase 3

Conditions

Anemia

Ischemic Heart Disease

Atrial Fibrillation

Chronic Arthritis

Bleeding

Treatments

Drug: Misoprostol

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02202967

2013-003187-31 (EudraCT Number)

GN09CA403

Details and patient eligibility

About

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

Full 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)

Enrollment

104 patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.