Efficacy of Nintedanib Per os as a Treatment for Epistaxis in HHT Disease.

Inclusion criteria

• Age > 18 years old
• 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 and/or with molecular biology confirmation
• Patient with an Epistaxis Severity Score (ESS) > 4

Exclusion criteria

• Pregnant woman or woman of child bearing potential
• Woman who are breast feeding.
• Patient who is protected adults under the terms of the law (French Public Health Code).
• Participation in another interventional clinical trial which may interfere with the proposed trial
• Active infection.
• (AST, ALT > 1,5 fold upper limit of normal (ULN) and/or Bilirubin > 1,5 fold upper limit of normal (ULN).
• Severe renal impairment
• Presence of non-treated pulmonary arteriovenous malformations accessible to a treatment on CT scan within 5 years.
• Patients with hemoptysis or hematuria within 12 weeks prior to inclusion.
• Patients with active gastro-intestinal (GI) bleeding or GI ulcers within 12 months prior to inclusion.
• Presence of cerebral arteriovenous malformation.
• Patients who require full-dose therapeutic anticoagulation (e.g. vitamin K antagonist or heparin, dabigatran) or high dose antiplatelet therapy, , patients under anticoagulation with rivaroxaban, apixaban and epixaban.
• Patients with P-glycoprotein (P-gp) substrates/inducers/inhibitors (e.g.: ketoconazole, erythromycin, cyclosporine, rifampicin, carbamazepine, phenytoin, and St. John's Wort).
• Patients with known coronary artery disease or recent history of myocardial infarction (within 1 year).
• Known inherited predisposition to thrombosis or thrombotic events( including stroke and transient ischemic attack, excluded superficial venous thrombosis) within 12 months prior to inclusion.
• Patients with QTc prolongation
• Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients.
• Patient who incompletely filled in epistaxis grids within 8 weeks prior to inclusion.
• Patient who have received intravenous bevacizumab within 6 months prior to inclusion.
• Patient who had surgery (including ENT (Ear, Nose and Throat Specialist) surgery) within 12 weeks prior to inclusion.
• Unhealed wound.
• Planned major surgery within the next 3 months, including liver transplantation, major abdominal or intestinal surgery.