Preparing and evaluating the effectiveness of topical cerosome of menthol on radial spasm and pain in patients with trans-radial angiography: a randomized, triple-blind, parallel placebo-controlled clinical trial.

One of the most prevalent complications associated with trans-radial angiography (TRA) is radial artery spasm (RAS). The purpose of this study is to prepare and assess the effectiveness of menthol cerosome, a topical nano-liposomal formulation, in preventing RAS, pain, and angiographic events, as well as clinical manifestations. Initially, cerosomes containing menthol and a placebo were prepared, and the drug formulation was characterized. Thereafter, a randomized, triple-blind, parallel, placebo-controlled clinical trial with 275 TRA-eligible patients was conducted. Thirty minutes prior to the angiographic procedure, patients were randomly assigned to receive either topical menthol cerosome (3.5%; 1 g applied to the wrist) or placebo cerosome (1 g). As the first outcome, RAS was identified clinically using a four-point composite scale and angiographically by operator-observed luminal narrowing impairing catheter movement, and radial pain was measured concomitantly using a visual analog scale (VAS). Heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were evaluated as indicators of sympathetic activity. During sheath insertion, the menthol cerosome group's physician-reported and self-reported VAS [median (interquartile range)] were significantly lower [3.0 (2.0) and 2.0 (2.0)] than the placebo group's (4.0 (2.0) and 3.0 (1.75)) (P < 0.001 for both cases). Additionally, menthol cerosome attenuated the increases in SBP (P < 0.001) and HR (P = 0.032) compared with the placebo group. Topical menthol cerosome decreased the angiographic RAS (6.7% vs. 21.4%, P < 0.001), clinical RAS (10.4% vs. 24.3%, P = 0.002), discomfort in the forearm while manipulating the catheter or sheath (7.4% vs. 18.6%, P = 0.006), catheter advancement difficulty (3.0% vs. 10.0%, P = 0.018), difficulty removing the sheath or catheter (3.0% vs. 13.6%, P = 0.001), and the requirement for further intra-arterial vasodilator administration to alleviate spasm (3.7% vs. 12.1%, P = 0.01) compared to the placebo group. In conclusion, the topical application of menthol cerosome was both safe and effective in reducing radial pain, angiographic failure, and RAS in patients undergoing TRA.