Prospective Comparison of ARNI Versus plAcebo in Patients With Congenital sYStemic Right Ventricle Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change of NT-proBNP level
研究概览
简要总结
This study is a prospective monocentric, randomized, double-blind, placebo-controlled, crossover clinical trial to assess the efficacy of Sacubitril/Valsartan over placebo in improving exercise capacity and neurohormonal activation in adults with moderate to severe systemic RV dysfunction and NYHA class II or III symptoms.
详细描述
Subjects who qualify will be approached and those consenting will be enrolled to undergo a baseline evaluation. An active run-in-phase of 6 weeks will identify each patient's maximal tolerated dose of Sacubitril/Valsartan. Then, each treatment arm (Sacubitril/Valsartan and placebo) will be 24 weeks duration prior to crossover. At the end of each study arm (24 weeks), data regarding primary and secondary endpoints will be collected. The total duration of the study for the patient will be 15 months.
Subjects will undergo regular visits (in-clinic, and/or by phone, or video conferencing) half-way and at the end of each arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A randomization sequence list will be performed by the statistical department. Patients will be randomized according to a computer-generated randomization sequence with 1:1 distribution using randomly permuted blocks of 4 and 6.
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 > or egal18 years with clinical follow-up at the Montreal Heart Institute Adult Congenital Heart Center
- •Systemic right ventricle (transposition of great vessels and atrial switch or congenitally corrected transposition of great vessels)
- •Moderate to severe systemic right ventricle dysfunction by transthoracic echocardiography (TTE) or right ventricle ejection fraction (RVEF) <40% by MRI
- •NYHA Functional class II-III symptoms or peak exercise capacity <80% of predicted on a previous standard treadmill exercise stress test (usually done every two years in our congenital clinic).
- •Ability to provide informed consent to the study
- •Access or own a telephone and/or access to internet connection for teleconference call
- •Own a mailing address to receive the medication by post (FedEx or Dicom)
- •Able to perform self-measurement of the blood pressure using Upper Arm Digital Blood Pressure Monitor as recommended by Hypertension Canada.
排除标准
- •Participation in a clinical trial of an investigational drug, concurrently, or within the last 30 days prior enrolment
- •Planned cardiac surgery (e.g., severe tricuspid regurgitation with planned tricuspid valve replacement or repair)
- •Previous cardiac transplantation, or on heart transplant wait list
- •Myocardial infarction, stroke, or open-heart surgery in the previous 4 weeks
- •NYHA Functional class I or IV symptoms
- •Symptomatic hypotension (fainting, dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache) with a systolic blood pressure <100 mmHg at screening, or asymptomatic <90 mmHg at screening
- •eGFR <30 mL/min/1.73 m2
- •Reduction in eGFR >35% from screening to randomization
- •Potassium >5.2 mmol/L at screening or >5.4 mmol/L at randomization
- •Known history of angioedema related to previous ACEI or ARB therapy or patients with a history of hereditary or idiopathic angioedema.
- •Patients who require concomitant treatment with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) or a renin inhibitor for other indication than heart failure
- •Evidence of hepatic disease as determined by any one of the following: serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) values exceeding 3x upper limit of normal, bilirubin >1.5 mg/dl at screening.
- •Unacceptable side effects with ACE-inhibitors or ARBs
- •Patient known with bilateral renal artery stenosis
- •Cyanosis; substantial left-to-right shunting (Qp/Qs >1.5); severe mitral, aortic, or pulmonary regurgitation; systemic or pulmonary inflow obstruction with a peak velocity >1.5 m/s by transthoracic echocardiography; and severe outflow tract obstruction with a peak systolic gradient >80 mm Hg.
- •Inability to provide informed consent
- •Unable to exercice
- •Pregnant or planned pregnancy during the study
- •Breastfeeding
- •Severe pulmonary hypertension defined as pulmonary pressure egal or superior to systemic pressure
研究组 & 干预措施
Placebo
Treatment with Placebo
干预措施: Placebo (Drug)
Sacubitril/Valsartan
Treatment with Sacubitril/Valsartan
干预措施: Sacubitril / Valsartan Oral Tablet (Drug)
结局指标
主要结局
Change of NT-proBNP level
时间窗: End of each arm treatment at 32 weeks and 58 weeks.
Co-primary endpoint (each at an alpha of 0.025): Change in NT-proBNP level between baseline and end of each treatment arm.
Change of sub-maximal total exercise duration
时间窗: End of each arm treatment at 32 weeks and 58 weeks.
Co-primary endpoint (each at an alpha of 0.025): change in sub-maximal total exercise duration during a sub-maximal cardiopulmonary exercise testing between baseline and end of each treatment arm.
次要结局
- Change of quality of life measured by Kansas City Cardiomyopathy Questionnaire-12 Score(End of each arm treatment at 32 weeks and 58 weeks.)
- Change of number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Half-way of each arm at 20 and 46 weeks and end of each arm treatment at 32 weeks and 58 weeks.)
研究者
Marie-Alexandre Chaix
Principal Investigator, Clinical Professor
Montreal Heart Institute