Efficacy of Nintedanib Per os as a Treatment for Epistaxis in HHT Disease. A National, Randomized, Multicentre Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 8
- 主要终点
- Epistaxis duration assessed on epistaxis grids completed by the patients.
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •Presence of cerebral arteriovenous malformation.
- •Patients who require full-dose therapeutic anticoagulation (e.g. vitamin K antagonist or heparin, dabigatran) or high dose antiplatelet therapy, , patients under anticoagulation with rivaroxaban, apixaban and epixaban.
- •Patients with P-glycoprotein (P-gp) substrates/inducers/inhibitors (e.g.: ketoconazole, erythromycin, cyclosporine, rifampicin, carbamazepine, phenytoin, and St. John's Wort).
- •Patients with known coronary artery disease or recent history of myocardial infarction (within 1 year).
- •Known inherited predisposition to thrombosis or thrombotic events( including stroke and transient ischemic attack, excluded superficial venous thrombosis) within 12 months prior to inclusion.
- •Patients with QTc prolongation
- •Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients.
- •Patient who incompletely filled in epistaxis grids within 8 weeks prior to inclusion.
- •Patient who have received intravenous bevacizumab within 6 months prior to inclusion.
- •Patient who had surgery (including ENT (Ear, Nose and Throat Specialist) surgery) within 12 weeks prior to inclusion.
- •Unhealed wound.
- •Planned major surgery within the next 3 months, including liver transplantation, major abdominal or intestinal surgery.
研究组 & 干预措施
Nintedanib
Oral treatment of Nintedanib 150 mg soft capsule
干预措施: Nintedanib 150 mg and 100 mg soft capsules (Drug)
Placebo
Oral treatment of placebo soft capsule
干预措施: Oral treatment of placebo soft capsule (Drug)
结局指标
主要结局
Epistaxis duration assessed on epistaxis grids completed by the patients.
时间窗: 12 weeks
次要结局
- 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)