Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.
研究概览
简要总结
Timolol is a nonselective β-blocker commonly used in the treatment of glaucoma. Recently it has been used topically for the treatment of superficial hemangiomas. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT). Moreover a case was reported in 2012 showing an improvement of nosebleeds with the use of topical nasal timolol. The aim of the study is to evaluate timolol nasal spray efficacy in HHT.
The main objective of this trial is to evaluate, 3 months after the end of the treatment, the efficacy on the duration of nosebleeds of a 4 weeks timolol intranasal treatment in HHT patients with nosebleeds (>20 min/month). Secondary objectives are to evaluate the tolerance, the efficacy at 6 months after the end of the treatment, and the efficacy on anemia and on clinical parameters (nosebleeds, quality of life and blood transfusions).
This is a prospective double blind phase II study, randomized versus placebo using an allocation ratio of 1:1. A total of 58 patients will be included. The product (solution with timolol at 0.5% or placebo) is self-administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 28 consecutive days.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients who give voluntary, informed consent and sign a consent form.
- •Patients affiliated with the French universal health care system
- •Patients treated for HHT, that has been confirmed clinically (presence of at least 3 Curaçao criteria) and/or by molecular biology.
- •Patients who present epistaxis averaging over 20 minutes in the three months before inclusion, justified by completed epistaxis tally sheets.
排除标准
- •Pregnant women or women who could become pregnant during the study, or during lactation
- •Patients not affiliated with the French universal health care system
- •Patients who are protected adults according to the terms of the law (French public health laws).
- •Refusal to give consent.
- •Patients whose HHT diagnosis has not be confirmed clinically and/or by molecular biology.
- •Participation in another therapeutic trial which could interfere with the present trial (investigator jugement).
- •Bronchial asthma, presence or history of severe chronic obstructive pulmonary disease
- •Cardiac history : cardiac failure or cardiogenic shock. Atrioventricular block (second or third degrees) not controlled with pace-maker or sinus disease (included sinoatrial block) confirmed by ECG less than one year. Ongoing treatment by calcium antagonists (bépridil, diltiazem, verapamil) or antiarrhytmics (propafénone, quinidine, hydroquinidine, disopyramide) or clonidine or lidocaîne. Ongoing beta-blocker treatment.
- •Bradycardia (<50 pulse per minute)
- •Hypotension (PAS < 90 Hg mm)
- •Not controlled Pheochromocytoma
- •Severe peripheral circulatory disturbances (Raynaud disease)
- •Hypersensitivity to the active substance, any of the excipients or other beta-blocking agents
- •Ongoing treatment by floctafénine or sultopride or amiodarone
- •Patients who do not complete epistaxis grids for three months before treatment
- •Patients who present epistaxis averaging below 20 minutes in the three months before inclusion
研究组 & 干预措施
Timolol
Timolol 0.5% eye-drops solution packaged in a nasal spray device.
干预措施: Timolol nasal spray (Drug)
Placebo
NaCl solution packaged in a nasal spray device.
干预措施: Placebo nasal spray (Drug)
结局指标
主要结局
Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.
时间窗: Day 0 (inclusion) ; up to 4 months
comparison of mean monthly epistaxis duration 3 months before the treatment and 3 months after the end of the treatment.
次要结局
- Efficacy on clinical criteria : epistaxis frequency .(Day 0 (inclusion) ; up to 4 months)
- Efficacy of timolol nasal spray on duration of nosebleeds for 6 months after the end of the treatment.(Day 0 (inclusion) ; up to 7 months)
- Tolerance of timolol nasal spray in patients with HHT-related epistaxis(up to 7 months)
- Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).(Day 0 (inclusion) ; up to 4 months)
- Efficacy on clinical criteria : quality of life (SF36).(Day 0 (inclusion) ; up to 4 months)