Evaluation of Sirolimus and Prednisolone Metasulfobenzoate Sodium in the Treatment of Superficial Arteriovenous Malformations

The primary objective of this study is to evaluate the efficacy of **sirolimus** (Rapamune) in reducing the "tumour" volume of superficial arteriovenous malformations through the analysis of angioscanographic changes. This is clinically relevant as it aims to provide a therapeutic option for managing these malformations, potentially improving patient outcomes by decreasing the size of the malformations and associated symptoms.

Secondary objectives include:

• Understanding how Rapamycin® contributes to therapeutic efficacy in these malformations.
• Explaining the pathophysiology of these malformations.

The clinical trial involves participants diagnosed with **superficial arteriovenous malformations**, specifically those classified as stage II+, III, or IV according to the Schöbinger classification (1994). The study population includes both male and female subjects, encompassing adults, adolescents, and children over the age of 2. Participants are required to be in good general health, with no significant vulnerabilities identified. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Key lifestyle considerations include the use of effective contraception during the study and for up to 12 weeks post-treatment, as well as a negative pregnancy test for women of childbearing age. The selection process for the trial population is based on the presence of progressive or quiescent lesions, with or without hemorrhagic phenomena, and informed consent is mandatory for participation.

The clinical trial is designed to evaluate the efficacy of **sirolimus** in the treatment of superficial arteriovenous malformations. This is a Phase IV, randomized, double-blind, controlled trial. The trial is expected to last until September 2026, with recruitment having commenced in September 2014. Participants will be involved in the study for a maximum treatment period of four months, with the primary endpoint being a 30% reduction in tumor volume as assessed by angioscannographic criteria within the first year. Secondary endpoints include the assessment of treatment efficacy at three, six, and nine months.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening visit, will determine participant eligibility based on criteria such as age, stage of the condition, and informed consent. Follow-up visits will occur at regular intervals to assess treatment efficacy and monitor any adverse effects. The end-of-study visit will conclude the participant's involvement, with a final assessment of the treatment's impact on the malformation.

Participants are expected to adhere to the study protocol, including the use of effective contraception during the study and for 12 weeks post-treatment. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide valuable insights into the therapeutic potential of sirolimus for this condition, contributing to the optimization of treatment strategies.

The clinical trial involves the administration of **Rapamune 1 mg coated tablets**, which contain the active substance **sirolimus**. This pharmaceutical form is a coated tablet intended for **oral use**. The maximum daily dose is 2 mg, with a total maximum dose of 2 mg per day. The treatment period is set for a maximum of 4 weeks. Sirolimus is a chemical substance, and its administration will be monitored to ensure participant compliance with the dosing schedule.

Additionally, the trial includes the use of **SOLUPRED 20 mg, comprimé orodispersible**, which contains **prednisolone metasulfobenzoate sodium** as the active ingredient. This medication is provided in the form of an orodispersible tablet, also for **oral use**. The maximum daily dose is 0.5 mg/kg, with a total maximum dose of 0.5 mg/kg per day, and the treatment period is limited to 1 week. Prednisolone metasulfobenzoate sodium is a chemical substance, and adherence to the dosing regimen will be closely monitored.

The trial also utilizes **SOLUPRED 5 mg, comprimé orodispersible**, which similarly contains **prednisolone metasulfobenzoate sodium**. This formulation is identical in pharmaceutical form and administration route to the 20 mg version, being an orodispersible tablet for **oral use**. The dosing parameters are consistent, with a maximum daily dose of 0.5 mg/kg and a total maximum dose of 0.5 mg/kg per day, over a treatment period of 1 week. Monitoring of participant compliance with the dosing schedule is an integral part of the study protocol.

The efficacy of the clinical trial titled "MAV-RAPA: Prospective evaluation of the efficacy of sirolimus (Rapamune) in the treatment of superficial arteriovenous malformations" will be assessed primarily through the reduction in the "tumour" volume of the malformation. This will be evaluated by analyzing angioscanographic changes. The primary endpoint is defined as the proportion of patients achieving a 30% reduction in **arteriovenous malformation (AVM)** tumour volume according to angioscanographic criteria during the first year of the study.

Secondary endpoints include the assessment of treatment efficacy at three, six, and nine months. These evaluations will provide additional insights into the temporal dynamics of the treatment's effectiveness. The trial will utilize angioscanography as a tool for measuring changes in tumour volume, ensuring that the assessments are both objective and quantifiable. The schedule for these assessments is structured to capture both immediate and longer-term effects of the treatment, thereby offering a comprehensive view of its efficacy over time.