Feasibility Trial for a Right Ventricular Failure Platform Trial

Launched by UNIVERSITY OF ALBERTA · Aug 22, 2024

Keywords

ClinConnect Summary

The CRAVE trial is a study designed to explore whether a larger trial can be successfully conducted to test new medications for patients with pulmonary hypertension and right ventricular dysfunction, which is a condition affecting the heart’s ability to pump blood effectively. In this trial, 30 participants will be randomly assigned to receive either standard care plus one of two medications (empagliflozin or ranolazine) or standard care alone. The goal is to see if these medications can help improve their heart function and overall health.

To be eligible for this trial, participants must be at least 18 years old and have a history of right heart problems. They should also be experiencing symptoms like shortness of breath or fatigue. Participants will need to provide informed consent and be able to follow the study procedures. Those who are pregnant, have certain heart or kidney issues, or are currently involved in other clinical trials may not be able to participate. If you join the study, you can expect regular check-ups, monitoring of your heart function, and support from the research team throughout the process.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age ≥ 18 years.
• • 2. Able to provide informed consent.
• • 3. Able to comply with all study procedures.
• 4. 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.
• • 5. Symptomatic with current NYHA Functional Class II-IV
• 6. Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:
• • 1. 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
• 2. 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).
• • 7. Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4 weeks.
• • 8. Access to an iOS or android smart phone or tablet.
• Exclusion Criteria:
• • 1. Estimated glomerular filtration rate (eGFR) \<30 ml/min.
• • 2. LVEF \< 50%
• • 3. Normal RV size and function
• • 4. Severe aortic or mitral valvular disease
• • 5. Moderate or severe hepatic dysfunction (Child-Pugh Class B or C)
• • 6. Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability
• • 7. Pregnancy or lactation
• • 8. Unable to provide consent and comply with follow-up visits
• • 9. Listed for lung, heart or heart/lung transplantation
• • 10. Myocardial infarction or acute coronary syndrome within 90 days of screening
• • 11. Enrolled in another interventional trial
• • 12. Planned cardiac or thoracic surgical intervention in the next 6 months.
• • 13. Known hypersensitivity to empagliflozin or ranolazine.
• 14. 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)
• • 15. Congenital long QT syndrome or a QTc interval \>500 ms