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

Launched by DR. ROMAIN LAZOR · Jul 14, 2021

Keywords

ClinConnect Summary

This clinical trial is studying the effect of a medication called nintedanib on reducing frequent nosebleeds, known as epistaxis, in patients with a condition called hereditary hemorrhagic telangiectasia (HHT). Currently, there are no available treatments to help manage these nosebleeds, which can be quite severe and bothersome. About 48 adult participants with HHT will take part in this study at the Lausanne University Hospital. They will keep a daily diary to track their nosebleeds for two months before starting the treatment. Then, for 16 weeks, they will take either nintedanib or a placebo (a pill with no active medication) and continue to record their experiences.

To be eligible for the trial, participants must be at least 18 years old and have a confirmed diagnosis of HHT along with moderate to severe nosebleeds. They should not have certain health conditions that could interfere with the study. Throughout the trial, participants will have regular check-ups and will be monitored for any side effects. This study is important as it may help find a new treatment for those suffering from frequent nosebleeds due to HHT, improving their quality of life.

Gender

ALL

Eligibility criteria

• 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.