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

• ClinicalTrials.gov Identifier: NCT02202967
• Recruitment Status: Completed
• First Posted: July 29, 2014
• Last Update Posted: August 14, 2018
• Sponsor: NHS Greater Glasgow and Clyde
• Information provided by (Responsible Party): NHS Greater Glasgow and Clyde

Tracking Information

• First Submitted Date: July 26, 2014
• First Posted Date: July 29, 2014
• Last Update Posted Date: August 14, 2018
• Actual Study Start Date: January 7, 2016
• Actual Primary Completion Date: October 11, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2018)

Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs. [ Time Frame: 8 weeks ]

Ulcers or smaller lesions (erosions) should totally disappear by the end of the study

• Original Primary Outcome Measures (submitted: July 28, 2014): Full healing of small bowel mucosal ulcers or erosions in response to misoprostol in users of aspirin or NSAIDs. [ Time Frame: 8 weeks ]
• Change History: Complete list of historical versions of study NCT02202967 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: August 12, 2018)

Change in the numbers of mucosal ulcers and erosions [ Time Frame: 8 weeks ]

Any increase or decrease in the numbers of ulcers and erosions will be measured at the end of the study

• Original Secondary Outcome Measures (submitted: July 28, 2014): Change in the numbers of mucosal erosions [ Time Frame: 8 weeks ]

Current Other Pre-specified Outcome Measures (submitted: August 12, 2018)

Change in blood haemoglobin level [ Time Frame: 8 weeks ]

Any rise or drop in the haemoglobin level will be measured at the end of the study

• Original Other Pre-specified Outcome Measures (submitted: July 28, 2014): Change in blood haemoglobin level [ Time Frame: 8 weeks ]

Descriptive Information

• Brief Title: Misoprostol for Small Bowel Ulcers and Obscure Bleeding Due to Aspirin or Nonsteroidal Antiinflammatory Drugs
• 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]
• 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)

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Misoprostol
  Misoprostol oral tablets/ capsules contain 200 mcg of Misoprostol, a synthetic prostaglandin E1 analog
  Other Name: Cytotec (R)
• Drug: Placebo
  Placebo contains lactose granules
  Other Name: Dummy drug

Study Arms

• Active Comparator: Misoprostol
  Misoprostol
  Intervention: Drug: Misoprostol
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 28, 2014): 104
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 11, 2017
• Actual Primary Completion Date: October 11, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02202967
• Other Study ID Numbers: GN09CA403; 2013-003187-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: NHS Greater Glasgow and Clyde
• Study Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: Not Provided

Investigators

• Study Director: Maureen Travers, PhD; NHS Greater Glasgow & Clyde, Scotland

• PRS Account: NHS Greater Glasgow and Clyde
• Verification Date: August 2018