Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study

Inclusion criteria

• General criteria:

• Age ≥ 18 years and < 70 years
• Subjects must have given their free and enlightened consent and have signed the consent form.
• HHT related criteria

• Patients monitored for clinically confirmed HHT disease.
• Patients with severe liver involvement in relationship with the HHT disease
• Patients with a high cardiac output on ultrasound.
• Associated disease related criteria

• Blood: neutrophil ≥ 1.0x109 / L and platelets ≥ 100x109 / L.
• INR (International Normalized Ratio) ≤ 1.5 (except for patients on anticoagulants) and TCA ≤ 1.5 x upper limit of the standard laboratory
• Renal function: creatinine ≤ 1.25 x upper limit of the standard laboratory. Patients who proteinuria to strip ≥ 2 + will have control of the Proteinuria of 24 hours to be ≤ 1g / 24 hours

Exclusion criteria

• • General criteria
• Women who are pregnant or liable to become pregnant in the course of the trial.
• Patients who have reached their majority but who are protected by the terms of the law (French public health code).
• Refusal to give enlightened consent.
• Patients who are not affiliated to a health insurance regime

• Criteria for the medical history
• Patients in whom the diagnosis of HHT disease has not been confirmed.
• The presence of atrial fibrillation on the electrocardiogram at the inclusion.
• The presence of cerebral arteriovenous malformations on the angioMRI done in the year prior to inclusion.
• Existence of diverticulitis of the colon or sigmoid
• Thrombosis within 6 months before inclusion
• Infectious disease treated by antibiotics and unresolved at inclusion.
• Patients with blood pressure that is not being controlled at the time of inclusion (systolic blood pressure> 150 mmHg and / or diastolic> 100 mmHg) with or without treatment. Patients who have high blood pressure can be included when the blood pressure numbers have been standardized by appropriate medical treatment.

• Surgical criteria
• Major surgery (including open biopsy) or severe trauma within 28 days preceding the start of treatment.

• Medical treatments
• Current or recent use of non steroidal anti-inflammatory drugs or antiplatelet therapy 10 days before the first administration of Bevacizumab.
• Use of oral or parenteral anticoagulants or thrombolytic agents within 28 days preceding inclusion (anticoagulants given prophylactically are permitted).
• Participation in another clinical trial within 28 days preceding inclusion.
• Vaccination with live vaccines or against yellow fever during the treatment period.
• Administration of phenytoin (Di-hydan ® DILANTIN ®) during the treatment period.

• Allergy
• Hypersensitivity to the active substance or any of its excipients.
• Hypersensitivity to products made from Chinese hamster ovary (CHO) cells or to any other human or humanized recombinant antibodies.