The recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis are spontaneous, very variable, may occur as often as several times every day, and are recurrent in 90% of patients and associated with chronic and severe anemia in 2-10%. They also significantly reduce quality of life. Blood transfusions are sometimes required in 10-30% of patients. Previous studies showed that antiangiogenic treatments such as anti-VEGF treatment (bevacizumab) administered intravenously was efficient on epistaxis and dramatically reduced nosebleeds. Tyrosine kinase inhibitors are anti-angiogenic molecules which are available orally and could therefore overcome the difficulties encountered with bevacizumab. The investigator hypothesized that nintedanib, acting by indirect inhibition of the VEGF receptor should allow a reduction of epistaxis in HHT patient. Nintedanib has been used in one HHT patient following the diagnosis of Insterstitial Pulmonary Fibrosis (published case report in 2017, Kovacs et al) with encouraging results. The aim is to evaluate efficacy of nintedanib for the treatment of epistaxis in HHT patients
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
61
Nintedanib 150 mg soft capsules twice daily approximately 12 hours apart (i.e. 300 mg/day) for 12 weeks. In case of adverse reaction a dose reduction at 200 mg/day (100 mg twice daily) can be prescribe.
Placebo soft capsules (identical to 150 mg and 100 mg soft capsules)
CHU d'Angers
Angers, France
Hôpital Femme-Mère-Enfant-Centre de Référence pour la maladie de Rendu-Osler
Bron, France
CHU Clermont Ferrand
Clermont-Ferrand, France
CHU de Marseille-Hôpital la conception
Marseille, France
CHU de Montpellier-Hôpital St Eloi
Montpellier, France
Hôpital Tenon
Paris, France
CHRU - Hôpital J.Bernard
Poitiers, France
CHU de Rennes-Hôpital Pontchaillou
Rennes, France
Epistaxis duration assessed on epistaxis grids completed by the patients.
Time frame: 12 weeks
number of adverse events
Time frame: 6 months
number of adverse events
Time frame: 12 weeks
number of adverse events
Time frame: 24 weeks
Efficacy or nintedanib assessed by ESS (Epistaxis Severity Score) questionnaire
This score assess the severity of epistaxis (minimum 0 corresponds to "none" and maximum 10 corresponds to"severe")
Time frame: 12 weeks
Efficacy or nintedanib assessed by ESS questionnaire
This score assess the severity of epistaxis (minimum 0 corresponds to "none" and maximum 10 corresponds to"severe")
Time frame: 24 weeks
duration of epistaxis all over the study. Assessment on epistaxis grids completed by the patients.
Time frame: 12 weeks
duration of epistaxis assessed on epistaxis grids completed by the patients.
Time frame: 24 weeks
duration of epistaxis assessed on epistaxis grids completed by the patients.
Time frame: 12 weeks
frequency of epistaxis assessed on epistaxis grids completed by the patients.
Time frame: 24 weeks
Quality of life assessed by SF36 (Short Form 36) questionnaire
Time frame: 12 weeks
Quality of life assessed by SF36 questionnaire
Time frame: 24 weeks
number of red blood cell transfusions
Time frame: 12 weeks
number of red blood cell transfusions
Time frame: 24 weeks
number of iron infusions
Time frame: 12 weeks
number of iron infusions
Time frame: 24 weeks
hemoglobin level
Time frame: 12 weeks
hemoglobin level
Time frame: 24 weeks
ferritin level
Time frame: 12 weeks
ferritin level
Time frame: 24 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.