Efficacy of Nintedanib for Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) Patients

Inclusion criteria: 1. signed informed consent 2. definite HHT disease (defined as the presence of a pathogenic mutation in one of the HHT genes, or the presence of 3 out of 4 Curaçao clinical criteria) 3. age ≥18 years at the time of informed consent 4. moderate to serious epistaxis defined as Epistaxis Severity Score (ESS) ≥2.5 5. absence of cerebral arteriovenous malformation demonstrated by brain imaging Exclusion criteria: 1. Women who are pregnant or breastfeeding 2. For women of childbearing potential (WOCBP, see Annex VII for definition), non-agreement to follow instructions for method(s) of contraception for the heterosexual couple (see Annex VII for instructions) during the treatment period and follow-up, or at least 3 months after the last dose of IMP, or if there are concerns that they will not reliably comply with the contraception requirements. 3. Acute infection 4. aspartate aminotransferase (AST), or alanine aminotransferase (ALT), or total bilirubin \>1.5x (or \>2.5x in patients known for Gilbert's syndrome) the upper limit of normal 5. Renal clearance by Cockcroft-Gault formula \<30 ml/min 6. Untreated pulmonary arteriovenous malformation (if vaso-occlusion is technically feasible) 7. Hemoptysis or hematuria within the last 12 months 8. Ulcus or active gastric bleeding within the last 12 months 9. Anticoagulant or antiplatelets treatment 10. Coronary heart disease 11. Thrombotic event within the last 12 months 12. Long QT syndrome (on ECG performed at screening) 13. Known allergy to nintedanib, soya, peanuts 14. Bevacizumab, pazopanib or other anti-angiogenic treatments within the last 12 months 15. Concomitant treatment with ketoconazole, erythromycin, rifampicin, carbamazepine, phenytoin, St John's Wort 16. Surgery within the last 3 months or planned within the next 9 months 17. Recent unhealed wound 18. Any other serious underlying medical condition that could interfere with the study treatment and potential adverse events 19. Any mental or other impairment that may compromise compliance with the study requirements.