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

NCT02202967 | Completed Phase 3 DMC

• 2 other identifiers: GN09CA4032013-003187-31
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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

Conditions

Chronic Arthritis; Ischemic Heart Disease; Atrial Fibrillation; Anemia; Bleeding

Keywords

Aspirin; Intestinal bleeding; Misoprostol; NSAIDs; Small intestine; Video capsule endoscopy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in the numbers of mucosal ulcers and erosions

  8 weeks

Other Outcomes (1)

• Change in blood haemoglobin level

  8 weeks

Study Arms (2)

Misoprostol

ACTIVE COMPARATOR

Misoprostol

Drug: Misoprostol

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Misoprostol DRUG

Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog

Also known as: Cytotec (R)

Misoprostol

Placebo DRUG

Placebo contains lactose granules

Also known as: Dummy drug

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead

Study Sites (1)

University Hospital Crosshouse

Kilmarnock, Scotland, KA2 0BE, United Kingdom

Location

Related 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. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):469-476. doi: 10.1016/S2468-1253(18)30119-5. Epub 2018 May 10.

  PMID: 29754836 RESULT

Related Links

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

MeSH Terms

Conditions

Myocardial Ischemia; Atrial Fibrillation; Anemia; Hemorrhage

Interventions

Misoprostol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Maureen Travers, PhD

  NHS Greater Glasgow & Clyde, Scotland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2014
• First Posted: July 29, 2014
• Study Start: January 7, 2016
• Primary Completion: October 11, 2017
• Study Completion: October 11, 2017
• Last Updated: August 14, 2018

Record last verified: 2018-08

Locations

GB (1)