Efficacy of Nintedanib for Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) Patients
Phase II Multicentric Randomized Study on Efficacy of Nintedanib for Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) Patients
Dr. Romain Lazor
48 participants
May 5, 2022
INTERVENTIONAL
Conditions
Summary
Patients affected by hereditary hemorrhagic telangiectasia (HHT) very often suffer from recurrent nosebleeds called epistaxis. There is no treatment currently available to reduce the frequency or severity of epistaxis. This research project will examine the effect of nintedanib, a capsule to be taken twice a day, on the frequency and severity of epistaxis in HHT. The study will take place at the Respiratory medicine department of the Lausanne University Hospital (Centre hospitalier universitaire vaudois, CHUV). The investigators will recruit about 48 participants with HHT, who will be divided in 2 groups. Each group will perform the same examinations and follow-up visits. The study will begin with 2 months of observation during which subjects will be asked to fill a diary to record the number and duration of epistaxis episodes. The diary will be filled daily for the entire duration of the study, i.e. 8 months. After 2 months of observation, the treatment phase will begin. Participants will take a capsule (nintedanib 150 mg or placebo) once a day for 2 weeks, then twice a day for 14 weeks. In case of intolerance at the dose of 2 capsules per day, the treatment may be reduced to 1 capsule per day. Subjects will also have to mention on the diary any blood transfusion, iron perfusion, and any symptoms they may be experiencing. Following the 16 weeks of treatment, an 8-week follow-up period will allow to observe the effects of nintedanib after the end of the treatment period, and to monitor any unexpected adverse events.
Eligibility
Inclusion Criteria5
- signed informed consent
- 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)
- age ≥18 years at the time of informed consent
- moderate to serious epistaxis defined as Epistaxis Severity Score (ESS) ≥2.5
- absence of cerebral arteriovenous malformation demonstrated by brain imaging
Exclusion Criteria19
- Women who are pregnant or breastfeeding
- 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.
- Acute infection
- 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
- Renal clearance by Cockcroft-Gault formula \<30 ml/min
- Untreated pulmonary arteriovenous malformation (if vaso-occlusion is technically feasible)
- Hemoptysis or hematuria within the last 12 months
- Ulcus or active gastric bleeding within the last 12 months
- Anticoagulant or antiplatelets treatment
- Coronary heart disease
- Thrombotic event within the last 12 months
- Long QT syndrome (on ECG performed at screening)
- Known allergy to nintedanib, soya, peanuts
- Bevacizumab, pazopanib or other anti-angiogenic treatments within the last 12 months
- Concomitant treatment with ketoconazole, erythromycin, rifampicin, carbamazepine, phenytoin, St John's Wort
- Surgery within the last 3 months or planned within the next 9 months
- Recent unhealed wound
- Any other serious underlying medical condition that could interfere with the study treatment and potential adverse events
- Any mental or other impairment that may compromise compliance with the study requirements.
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Interventions
150 mg oral nintedanib soft caps, once a day for 2 weeks and twice a day for 10 weeks (12 hours interval)
150 mg oral placebo soft caps, once a day for 2 weeks and twice a day for 10 weeks (12 hours interval)
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04976036