Topical sirolimus therapy for cutaneous vascular anomalies: A randomized phase II clinical trial.

The efficacy, safety, and optimal concentration of topical sirolimus gel for treatment of cutaneous lesions of vascular anomalies requires evaluation. This study was a multicenter, double-blind, placebo-controlled, parallel-group, phase II randomized clinical trial. We enrolled patients with venous malformation (n = 27), lymphatic malformation (n = 14), tufted angioma (n = 8), or kaposiform hemangioendothelioma (n = 1). Patients applied either placebo or 0.2% or 0.4% topical sirolimus gel to the target lesion twice per day for 12 weeks. The primary endpoint was the overall improvement score in the target lesion assessed from photographs by the independent review committee at Week 12. There was no statistically significant difference in the mean improvement score in the 0.2% group (p = 0.410) or the 0.4% group (p = 0.549) compared with in the placebo group. Thus, we could not prove the efficacy of topical sirolimus for cutaneous vascular anomalies in this protocol. Conversely, the improvement in target lesion size at Week 12 assessed by the committee as one of the 16 secondary endpoints was significantly higher in the 0.4% sirolimus gel group than in the placebo group (p = 0.031). In the post-hoc analysis outside the protocol tracing the contour of the lesion, the percentages of patients with ≥20% reduction in the lesion area increased dose-dependently (0%, 37.5%, and 65.0% in the placebo, 0.2%, and 0.4% group, respectively). Regarding safety, irritation and dermatitis at the application site occurred in the 0.4% gel group. Sirolimus gel reduced lesion size in our cohort. The safety data demonstrated topical sirolimus to have an acceptable safety profile.