Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations

Inclusion Criteria:

• Patients (adults, adolescents and children older than 2 years), with arteriovenousmalformation stage II + III or IV (according to Schöbinger's classification) :active or quiescent, marked or not by hemorrhagic phenomena.

• Patients (parents for minors) must sign a consent form established after clearinformation risks and expected benefits of the study.

• Patients (major and minor of childbearing age) must have effective contraceptionduring the study period and continuing until 12 weeks after the end of treatment

• Negative pregnancy blood test for women of childbearing age.

Exclusion Criteria:

• Chronic or acquired immunosuppression :

• patients with transplanted organ or who received a hematopoietic stem cell

• patient with congenital immunodeficiency

• Patients implanted with chronic active infection associated with hepatitis B ,hepatitis C or HIV

• Pregnant or nursing woman.

• Allergy to macrolides

• Allergy to peanut or soya

• Hypersensitivity to " Sirolimus " or any of the excipients of the investigationalproduct

• Contraindications to performing an MRI

• Leukopenia below 1 000 /mm3

• Thrombocytopenia lower to 80,000 /mm3

• Anemia with Hb < 9 g/dl

• Elevated transaminase > 2.5 N

• History of cancer less than two years before the inclusion

• Surgery older than 2 months before inclusion

• Active infection (viral and bacterial ) on the date of inclusion

• Hypercholesterolemia > 7 mmol / l despite appropriate medical treatment

• Hyperlipidemia > 2 mmol / l despite appropriate medical treatment

• Uncontrolled diabetes

• Patients unable to follow a clinical study

• Major under guardianship, persons deprived of their liberty