Feasibility assessment of treatments for right ventricular failure

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

This study is testing if adding two different medications to standard care can help people with right heart failure and pulmonary hypertension feel better and if it's possible to do a bigger study in the future.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Alberta (Academic / other)
• Locations: 5 sites (Calgary, Alberta and 4 other locations)
• Trial ID: NCT06570473 on ClinicalTrials.gov

What this trial studies

This trial aims to evaluate the feasibility of a larger platform trial focused on improving right ventricular function in patients with pulmonary hypertension and right heart failure. It involves a randomized control design with 30 participants who will receive either empagliflozin or ranolazine in addition to standard care, or standard care alone. The study will follow participants for 16 weeks to assess outcomes related to their condition. The goal is to determine if these treatments can be effectively tested in a larger study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with symptomatic right ventricular dysfunction or right heart failure due to specific types of pulmonary hypertension.

Not a fit: Patients with conditions unrelated to pulmonary hypertension or those who do not meet the eligibility criteria may not benefit from this trial.

Why it matters

Potential benefit: If successful, this trial could lead to improved treatment options for patients suffering from right ventricular dysfunction and pulmonary hypertension.

How similar studies have performed: While this approach is novel in its specific focus, similar studies have shown promise in exploring treatments for pulmonary hypertension and right heart failure.

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

Where this trial is running

Calgary, Alberta and 4 other locations

• University of Calgary — Calgary, Alberta, Canada (Not_yet_recruiting)
• University of Alberta — Edmonton, Alberta, Canada (Recruiting)
• The University of British Columbia — Vancouver, British Columbia, Canada (Not_yet_recruiting)
• London Health Sciences Centre - University Hospital — London, Ontario, Canada (Not_yet_recruiting)
• The Ottawa Hospital — Ottawa, Ontario, Canada (Not_yet_recruiting)

Study contacts

• Principal investigator: Jason Weatherald, MD,MSc,FRCPC — University of Alberta
• Study coordinator: Jason Weatherald, MD,MSc,FRCPC

Conditions Pulmonary Hypertension; Right Ventricular Dysfunction; Right Heart Failure; Empagliflozin; Ranolazine