The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. There is currently no standard and efficient management of this severe symptom. It is also well known that HHT-associated hemorrhages have the greatest negative impact on quality of life among HHT patients, and is responsible for anemia, blood transfusions, hospitalizations, depressive syndrome and a high psycho-social impact.

Since 2006, it has been suggested by animal models and then by clinical reports that anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages.

Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a reduction was observed in the duration of the nosebleeds after treatment and was encouraging to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model in order to assess the individual concentration-effect relationship of bevacizumab.

However, no randomized prospective study has been performed and published to evaluate the efficacy in this indication. A total of 24 patients will be randomized versus placebo in a multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days with a total of 6 cures with a 3 months following period.

Inclusion Criteria:

• Age ≥ 18 years.
• Patients who have given their free informed and signed consent.
• Patients affiliated to a social security scheme or similar.
• Patients monitored for clinically confirmed HHT (presence of at least three Curaçao criteria) and / or with molecular biology confirmation.
• Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding.

Exclusion Criteria:

• Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose.
• Patients who are protected adults under the terms of the law (French Public Health Code).
• Refusal to consent.
• Patients for whom the diagnosis of HHT has not been confirmed clinically and / or by molecular biology study.
• Active infection and/or fever>38°C
• Participation in another clinical trial within 28 days prior to inclusion.
• Hypersensitivity to the active substance or to any of the excipients.
• Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other recombinant human or humanized antibodies.
• Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion.
• Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT surgery for epistaxis will have to wait at least 3 months less after treatment to be included if bleeding persists.
• Patients who had a surgery in the month prior inclusion or planned surgery within 6 months
• Severe peripheral arterial disease with ulcerations
• Unhealed wound
• Thrombosis in the 6 months prior to inclusion
• Anticoagulant treatment
• Uncontrolled high blood pressure