Efficacy of a Timolol Gel in the Care for Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia: A Double-Blinded, Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up
研究概览
简要总结
This study is a double-blinded, randomized controlled trial to evaluate the efficacy of an intranasal topical timolol gel in the care for epistaxis in adults with hereditary hemorrhagic telangiectasia.
详细描述
This study is a double-blinded, placebo-controlled, 8-week randomized clinical trial investigating the efficacy of timolol gel in the management of epistaxis in adults with HHT.
The Specific Aims are to determine in adults with HHT-associated epistaxis:
- If topical timolol gel is more effective than placebo in reducing the frequency and severity of epistaxis.
- If topical timolol gel is more effective than placebo in improving hemoglobin levels.
- The frequency of adverse events, side effects, and safety profile of topical timolol gel delivered to the nasal mucosa.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ages 20 and older
- •Confirmed clinical (meeting at least 3 of the 4 Curaçao Criteria) or genetic diagnosis of HHT
- •Epistaxis Severity Score (ESS) ≥ 4 and 2 or more nosebleeds per week with a cumulative nosebleed duration of at least 5 minutes per week
- •Stable nasal hygiene and medical regimen for preceding 1 month
- •Stable epistaxis pattern over the preceding 3 months
排除标准
- •Contraindications for systemic β adrenergic blocker administration
- •Hypersensitivity to β adrenergic blockers
- •Asthma or bronchospasm
- •Congestive heart failure with LVEF <40%
- •Hereditary pulmonary arterial hypertension
- •Baseline bradycardia (HR <55 beats per minute)
- •Sick Sinus Syndrome
- •2nd or 3rd degree heart block, left or right bundle branch block, or bifasicular block
- •Uncontrolled diabetes mellitus (most recent HbA1c >9%) or diabetic ketoacidosis within last 6 months
- •Hypotension (systolic blood pressure < 90)
- •Known hypersensitivity to timolol
- •Severe peripheral circulatory disturbances (Raynaud phenomenon)
- •Known intermediate or poor metabolizer variant of the liver enzyme CYP2D6
- •Current use of any of the following known strong CYP2D6 inhibitors: fluoxetine (Prozac), paroxetine (Paxil), bupropion (Welbutrin), quinidine, quinine, ritonavir (Norvir), and terbinafine (Lamisil)
- •Current use of the following other drugs known to pharmacodynamically interact with timolol: diltiazem, verapamil, digoxin, digitalis, propafenone, disopyramide, clonidine, flecainide, or lidocaine
- •Patients currently treated or who plan to initiate treatment with β-blockers
- •Use of any anti-angiogenic medication in the last month prior to recruitment, including bevacizumab, pazopanib, thalidomide, or lenalidomide
- •Illicit drug use, except marijuana
- •Known pheochromocytoma
- •Use of anticoagulants, antiplatelet, or fibrinolytic therapies within the last month prior to recruitment, except for low-dose (81 mg or less) of aspirin
- •Pregnancy or planned pregnancy in the next 6 months or currently breastfeeding
- •Inability to read or understand English
- •Inability to complete 8 weeks of therapy for any reason
研究组 & 干预措施
Timolol Gel Arm
Participants in the timolol gel arm (active medication arm) will receive timolol nasal gel 0.1% with 0.5 mL applied to each nostril twice daily via a syringe that will amount to a 2 mg total daily dose.
干预措施: Timolol Gel (Drug)
Placebo Gel Arm
Participants in the placebo gel arm will receive the gel itself with no active medication.
干预措施: Placebo Gel (Drug)
结局指标
主要结局
Change in Assisted Epistaxis Severity Scale (aESS) Score From Baseline at 8 Week Follow-up
时间窗: Baseline to 8-week follow-up
Assessment of epistaxis severity will be obtained by the validated instrument, the Epistaxis Severity Score (ESS). To complete the ESS, patients are asked to consider typical symptoms over the previous 3 months. The ESS contains 6 items - frequency, duration, and intensity of nosebleeds, whether patient has sought medication attention, whether patient is anemic, and whether patient has received a blood transfusion. The overall score ranges from 0 to 10, with severity of nosebleed based on score graded as None composite score of 0-1, Mild 1-4, Moderate 4-7, and Severe as 7-10.The minimal important difference noticeable by both patients and clinicians in the ESS scoring system is estimated as a change of 0.71. The scoring and MCID of the aESS is the same as the ESS. The aESS references a participant's epistaxis over the past 1 month, and the change in aESS was calculated as the aESS score at 8 weeks minus the aESS score at baseline.
次要结局
- Number of Participants With Improved Response on Clinical Global Impression - Improvement (CGI-I) Scale(Scores at 8-week follow-up only)
研究者
Jay F. Piccirillo, MD
Professor and Vice Chair for Research, Department of Otolaryngology - Head and Neck Surgery
Washington University School of Medicine