RecruitingPhase 2NCT06570473

Feasibility Trial for a Right Ventricular Failure Platform Trial

Feasibility Trial for the Canadian Right Ventricular AdaptiVE (CRAVE) Platform for Therapies Targeting Right Ventricular Failure

Sponsor

University of Alberta

Enrollment

30 participants

Start Date

Jul 15, 2025

Study Type

INTERVENTIONAL

Conditions

Pulmonary Hypertension Right Ventricular Dysfunction Right Heart Failure

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria12

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.

Exclusion Criteria18

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