Feasibility Trial for the Canadian Right Ventricular AdaptiVE (CRAVE) Platform for Therapies Targeting Right Ventricular Failure
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Average enrolment rate of participants per centre per month
研究概览
简要总结
The primary objective of the CRAVE feasibility trial is to assess the feasibility of conducting a larger CRAVE platform trial by performing a randomized trial of 30 participants with pulmonary hypertension and right ventricular dysfunction, comparing empagliflozin or ranolazine plus standard of care to standard of care alone.
详细描述
This study is an investigator-initiated, open label, prospective, multi-centre, phase 2, randomized control trial. This CRAVE feasibility trial will seek to establish the feasibility of a larger platform trial for testing multiple interventions in various domains to improve right ventricular function. In this feasibility trial, 30 participants with pulmonary hypertension and right heart failure with be randomized 1:1:1 to empagliflozin 10 mg daily + standard of care, ranolazine twice daily + standard of care, or standard of care alone. Participant outcomes (medical records review) will be followed for 16 weeks after randomization.
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
- None
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.
- •Able to provide informed consent.
- •Able to comply with all study procedures.
- •History of RV dysfunction or RHF secondary to any of:
- •a. Group 1 PH, pulmonary arterial hypertension b. Group 2 PH, left heart disease with normal left ventricular ejection fraction (LVEF) > 50% and a previous RHC demonstrating combined pre and post-capillary PH, defined as: i. mPAP >20 mmHg ii. PAWP > 15 mmHg iii. PVR> 2 WU c. Group 3 PH d. Group 4 PH, chronic thromboembolic PH that is either persistent after pulmonary endarterectomy or inoperable due to distal disease.
- •Symptomatic with current NYHA Functional Class II-IV
- •Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:
- •NT-proBNP >300 ng/L and qualitative evidence of at least 'mild' RV dysfunction on echocardiography OR NT-proBNP<300 ng/L and qualitative evidence of at least moderate RV dysfunction and/or dilatation on 2D echocardiogram AND
- •A quantitative 2D echocardiogram with evidence of RV dysfunction defined as having both of the following:
- •i. TAPSE ≤18 mm ii. RV dilatation (RV diameter > 42 mm at the base).
- •Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4 weeks.
- •Access to an iOS or android smart phone or tablet.
排除标准
- •Estimated glomerular filtration rate (eGFR) <30 ml/min.
- •LVEF < 50%
- •Normal RV size and function
- •Severe aortic or mitral valvular disease
- •Moderate or severe hepatic dysfunction (Child-Pugh Class B or C)
- •Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability
- •Pregnancy or lactation
- •Unable to provide consent and comply with follow-up visits
- •Listed for lung, heart or heart/lung transplantation
- •Myocardial infarction or acute coronary syndrome within 90 days of screening
- •Enrolled in another interventional trial
- •Planned cardiac or thoracic surgical intervention in the next 6 months.
- •Known hypersensitivity to empagliflozin or ranolazine.
- •Concurrent treatment with:
- •strong inhibitors of Cytochrome P450 3A4 (CYP 3A4), (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, nelfinavir, ritonavir, indinavir, saquinavir and grapefruit juice)
- •class IA antiarrhythmics (e.g., quinidine, procainamide, disopyramide) or class III antiarrhythmics (e.g., sotalol, ibutilide, amiodarone, dronedarone)
- •inducers of CYP 3A4 (e.g., rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort)
- •Congenital long QT syndrome or a QTc interval >500 ms
研究组 & 干预措施
Empagliflozin
Participants in the empagliflozin arm will receive 10 mg by mouth once daily and standard of care.
干预措施: Empagliflozin (Drug)
Ranolazine
Participants in the ranolazine arm will receive ranolazine 500 mg by mouth twice daily, which will be increased to 1000 mg twice daily after 2 weeks (unless concurrently using moderate CYP 3A4 inhibitors, then dose is limited to 500 mg twice daily) and will receive standard of care.
干预措施: Ranolazine (Drug)
结局指标
主要结局
Average enrolment rate of participants per centre per month
时间窗: 16 weeks
(target ≥1 participant per centre/month)
The proportion of eligible participants approached that consent
时间窗: 16 weeks
(target ≥30%)
The proportion of participants who consent that are randomized
时间窗: 16 weeks
(target ≥90%)
Loss of follow up or death
时间窗: 16 weeks
Loss of follow up (target at 16 weeks ≤5%)
Ability to capture data for secondary outcomes
时间窗: 16 weeks
(target ≥90% completion)
次要结局
- Natriuretic peptides(16 weeks)
- Clinical event outcomes(16 weeks)
- Exercise capacity measured virtually(16 weeks)
- Exercise capacity measured in-person(16 weeks)
- NYHA functional class(16 weeks)
- EmPHasis-10(16 weeks)
- RV function(16 weeks)
- Hemodynamics(16 weeks)
- KCCQ-12(16 weeks)
- EQ-5D-5L(16 weeks)