Objective of the trial.
bleeding, vascular malformation, slow-flow vascular malformations, pain, vascular malformation-related, oozing
ADVERSE EVENT, BLEEDING, RECURRENCE, MOS, INFECTIONS
The primary objectives were to assess the efficacy of sirolimus for the treatment of slow-flow vascular malformations and to evaluate the associated safety profile in children and adults. The efficacy assessment of sirolimus at each visit was based on the following.Patient self-assessment of the vascular malformation-related general evolution with sirolimus compared with last visit: improvement, stability or worsening.Evaluation of symptoms focused on pain (intensity of continuous pain and frequency/intensity of pain exacerbation), functional limitation, bleeding, oozing, and repetitive infections. The evaluation of pain (continuous and exacerbation) including the intensity based on visual analog scale (VAS), ranging from 0 (no pain) to 10 (excessive pain), and the frequency of pain exacerbations (number of crises per month). The evaluation of functional limitation (difficulties in performing any action of everyday life) based on a scale ranging from 0 (no limitation) to 10 (excessive limitation).Size of the lesion on the basis of clinical evaluation and measurement with calipers at each consultation, and radiological comparison between baseline and 1- and 2-year MRI).Other exploratory endpoints included the time interval between the end of treatment (after 2 years of treatment per protocol) and symptom recurrence, the efficacy of sirolimus based on vascular malformation type and/or genomic alteration, and the rate of subsequent surgery and/or sclerotherapy that became possible by sirolimus.Health-related QoL (HRQoL) was evaluated at baseline and at each consultation based on a questionnaire modified from the RAND MOS SF-36 Survey (Lack of benefit was defined as (a) patients who discontinued sirolimus prematurely for absence of efficacy and (b) patients who stopped sirolimus for AEs/noncompliance and without clinical benefit.AEs were assessed according to the Common Terminology Criteria for Adverse Events v5.0 (