Taha AS, et al. - In this randomised, double-blind, placebo-controlled, phase 3 trial, the researchers evaluated the efficacy and safety of misoprostol for the treatment of small bowel ulcers and erosions in patients taking low-dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) with obscure gastrointestinal bleeding. In patients using low-dose aspirin and NSAIDs, misoprostol was effective for the treatment of small bowel ulcers and erosions. Findings suggested that misoprostol could represent a pharmacological treatment option for lesions causing obscure gastrointestinal bleeding that was correlated with aspirin and NSAIDs, but its use should be balanced against the risk of side-effects.

Methods

• Study participants were patients (aged ≥18 years) with small bowel ulcers who were taking low-dose aspirin, NSAIDs, or both for a minimum of 4 weeks, at University Hospital Crosshouse (Kilmarnock, UK).  
• Evidence of obscure gastrointestinal bleeding (iron deficiency anaemia, a decrease in haemoglobin concentration of ≥20 × 10³ mg/L, or positive faecal occult blood test) and normal upper endoscopy and colonoscopy was found in eligible subjects.
• After that, subjects were randomly assigned (1:1) using an interactive voice response system to receive 200 μg oral misoprostol or placebo four times daily for 8 weeks.
• Patients, investigators, and assessors were masked to treatment allocation.
• The complete healing of small bowel ulcers and erosions, assessed by video capsule endoscopy after 8 weeks of treatment was the primary endpoint.
• Primary analysis was by modified intention to treat, which involved all randomised subjects who received at least one dose of study treatment.
• Safety was evaluated in the same population.

Results

• One hundred four eligible patients were randomly allocated: 52 to receive misoprostol and 52 to receive placebo between Jan 7, 2016, and Oct 11, 2017.
• Researchers reported that 2 subjects allocated to misoprostol were later found to meet one of the exclusion criteria, thus 50 randomly assigned subjects in the misoprostol group and 52 subjects in the placebo group received at least one dose of study treatment.
• They observed complete healing of small bowel ulcers and erosions at week 8 in 27 (54%) of 50 patients in the misoprostol group and nine (17%) of 52 patients in the placebo group (percentage difference 36·7%, 95% CI 19·5–53·9; p=0·0002).
• It was noted that adverse events occurred in 23 (46%) of 50 patients in the misoprostol group and 22 (42%) of 52 patients in the placebo group.
• Abdominal pain (ten [20%] in the misoprostol group vs 13 [25%] in the placebo group), nausea or vomiting (nine [18%] vs seven [13%]), and diarrhoea (11 [22%] vs six [12%]) were the most common adverse events.
• In the misoprostol group, 4 (8%) of 50 patients had severe adverse events, compared with none in the placebo group.
• According to the findings obtained, no serious adverse events were reported.