Efficacy of spraying l-menthol solution during endoscopic treatment of early gastric cancer: A phase III, multicenter, randomized, double-blind, placebo-controlled study

Background: The topical antispasmodic agent l-menthol is useful for inhibiting gastric peristalsis during diagnostic upper gastrointestinal endoscopy. However, it remains unclear whether l-menthol is similarly effective during therapeutic endoscopy, thereby improving treatment outcomes in a clinical setting. Methods: A total of 83 patients scheduled to undergo endoscopic treatment at 8 Japanese referral centers were randomly assigned to receive l-menthol or placebo. The degree of gastric peristalsis (peristaltic score: grade 1-5) was assessed by an independent committee. The primary outcome was the proportion of subjects in whom no or mild peristalsis (grade 1 or 2) was maintained throughout endoscopic treatment. Secondary outcomes were the duration of sustained response and the incidence of adverse drug reactions. Results: The proportion of patients with no or mild peristalsis was significantly higher in the l-menthol group (85.4 %, 95 % confidence intervals 70.8-94.4: 35/41 subjects) than in the placebo group (39.0 %, 24.2-55: 16/41; P < 0.001). The sustained response rates in the l-menthol and the placebo were, respectively, 90.0 and 39.6 % 30 min post-dose, and 79.9 and 35.7 % at the completion of the resection. The sustained response rates were significantly higher in the l-menthol group than in the placebo group (P < 0.001, log-rank test). The incidence of adverse drug reactions did not differ significantly between the two groups (P = 1.000). Conclusions: During gastric endoscopic submucosal dissection, spraying l-menthol on the gastric mucosa significantly suppressed peristalsis, with minimal adverse drug reactions as compared with placebo. l-menthol solution might be useful for therapeutic endoscopy.