Empagliflozin + Ranolazine for Right Ventricular Dysfunction

(CRAVE Trial)

Recruiting at 4 trial locations

Overseen By Courtney Gubbels, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must be taking: Loop diuretics, mineralocorticoid antagonists

Must not be taking: CYP 3A4 inhibitors, antiarrhythmics

Disqualifiers: Low eGFR, Pregnancy, Transplantation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, such as strong inhibitors or inducers of Cytochrome P450 3A4, certain antiarrhythmics, and others. If you are on these medications, you may need to stop them to participate.

How is the drug combination of Empagliflozin and Ranolazine unique for treating right ventricular dysfunction?

The combination of Empagliflozin and Ranolazine is unique because Empagliflozin has shown benefits in reducing heart failure hospitalizations and cardiovascular deaths in patients with heart failure, while Ranolazine is known for its anti-anginal effects. This combination may offer a novel approach by targeting both heart failure and angina symptoms, which is not typically addressed by standard treatments for right ventricular dysfunction. ^{1 2 3 4 5}

Research Team

Jason Weatherald, MD,MSc,FRCPC

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for adults over 18 with pulmonary hypertension and right ventricular dysfunction who can follow the study procedures. They must have certain types of pulmonary hypertension, symptoms matching NYHA Functional Class II-IV, specific heart function measurements on tests, and be on certain heart medications for at least 4 weeks.

Inclusion Criteria

Able to provide informed consent

Able to comply with all study procedures

Access to an iOS or android smart phone or tablet

Exclusion Criteria

LVEF < 50%

Pregnancy or lactation

Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either empagliflozin, ranolazine, or standard of care for right ventricular failure

16 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin
• Ranolazine

Trial Overview The CRAVE feasibility trial is testing whether it's possible to do a bigger study on two drugs: Empagliflozin or Ranolazine plus standard care versus just standard care in people with pulmonary hypertension and right ventricular dysfunction. It's a small test run with 30 participants.

Participant Groups

Group I: Ranolazine Experimental Treatment 1 Intervention

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.

Group II: Empagliflozin Experimental Treatment 1 Intervention

Participants in the empagliflozin arm will receive 10 mg by mouth once daily and standard of care.

Group III: Standard of Care Active Control 1 Intervention

Participants in this group will receive standard of care.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Team PHenomenal Hope

Collaborator

Trials

1

Recruited

30+

Canadian Heart Function Alliance

Collaborator

Trials

2

Recruited

1,400+

Accelerating Clinical Trial (ACT) Consortium

Collaborator

Trials

1

Recruited

30+

Ottawa Heart Institute Research Corporation

Collaborator

Trials

200

Recruited

95,800+

Findings from Research

Empagliflozin (EMPA) significantly reduced the induction of ventricular fibrillation (VF) in an ex-vivo model of ischemia-reperfusion, with only 16.7% of EMPA-treated hearts experiencing VF compared to 60% in control hearts.

EMPA improved cardiac contractility, as shown by a higher left ventricular developed pressure (LVDP) and enhanced calcium cycling, indicating its potential to protect heart function during ischemic events through mechanisms that do not involve sodium-glucose co-transporter-2 (SGLT2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. Azam, MA., Chakraborty, P., Si, D., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Heart failure outcomes according to heart rate and effects of empagliflozin in patients of the EMPEROR-Preserved trial. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-arrhythmic and inotropic effects of empagliflozin following myocardial ischemia. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Dapagliflozin and Empagliflozin in Heart Failure with Reduced Ejection Fraction: A Retrospective Study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Public Health Impact and Cost-Effectiveness of Empagliflozin (JARDIANCE&#174;) in the Treatment of Patients with Heart Failure with Preserved Ejection Fraction in France, Based on the EMPEROR-Preserved Clinical Trial. [2023]