Efficacy of Nintedanib Per os as a Treatment for Epistaxis in HHT Disease. A National, Randomized, Multicentre Phase II Study
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 61
- Locations
- 8
- Primary Endpoint
- Epistaxis duration assessed on epistaxis grids completed by the patients.
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Nintedanib
Oral treatment of Nintedanib 150 mg soft capsule
Intervention: Nintedanib 150 mg and 100 mg soft capsules (Drug)
Placebo
Oral treatment of placebo soft capsule
Intervention: Oral treatment of placebo soft capsule (Drug)
Outcomes
Primary Outcomes
Epistaxis duration assessed on epistaxis grids completed by the patients.
Time Frame: 12 weeks
Secondary Outcomes
- hemoglobin level(24 weeks)
- number of adverse events(24 weeks)
- Efficacy or nintedanib assessed by ESS (Epistaxis Severity Score) questionnaire(12 weeks)
- Efficacy or nintedanib assessed by ESS questionnaire(24 weeks)
- Quality of life assessed by SF36 (Short Form 36) questionnaire(12 weeks)
- number of iron infusions(24 weeks)
- ferritin level(24 weeks)
- duration of epistaxis all over the study. Assessment on epistaxis grids completed by the patients.(12 weeks)
- Quality of life assessed by SF36 questionnaire(24 weeks)
- duration of epistaxis assessed on epistaxis grids completed by the patients.(12 weeks)
- frequency of epistaxis assessed on epistaxis grids completed by the patients.(24 weeks)
- number of red blood cell transfusions(24 weeks)