Empagliflozin + Carvedilol for Cardiotoxicity

Recruiting at 1 trial location

Overseen By Sang Gune Yoo, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Beta blockers, SGLT2 inhibitors

Must not be taking: Non-dihydropyridine calcium blockers

Disqualifiers: Untreated brain metastases, Prior anthracyclines, 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: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if carvedilol (a beta blocker) and/or empagliflozin (a diabetes medication) can prevent heart issues in individuals with HER2-positive breast cancer who are starting or have recently started HER2-targeted therapy. The study will evaluate these medications alone and in combination to assess their safety and effectiveness in protecting the heart during cancer treatment. Individuals diagnosed with HER2-positive breast cancer who are about to begin or have recently begun HER2-targeted treatment may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking any SGLT2 inhibitors or beta blockers if you are currently on them and cannot stop during the study. If you are on a non-dihydropyridine calcium channel blocker, it must be transitioned to or used with carvedilol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that carvedilol lowers the risk of heart problems by 58% in patients receiving cancer treatment. It was generally safe and tolerable for breast cancer patients. Carvedilol, a beta blocker, helps manage heart issues.

Research on empagliflozin, another drug under testing, indicates it can reduce the risk of heart-related deaths and hospital visits. It has been linked to a 14-38% decrease in major heart events. This drug, an SGLT2 inhibitor, helps control heart problems, especially in people with certain types of diabetes.

When used together, carvedilol and empagliflozin appear as safe as when used separately. Studies suggest no major safety differences compared to usual care. Both drugs are generally well-tolerated, meaning most people can take them without serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore a new combination approach for managing cardiotoxicity. Unlike the standard of care, typically involving beta-blockers like carvedilol alone, this trial investigates the added benefits of empagliflozin, a medication primarily used for diabetes, which also shows promise in protecting the heart. Empagliflozin works by excreting glucose through the urine, potentially reducing cardiac strain, while carvedilol helps by reducing blood pressure and heart rate. This combo could offer a dual-action benefit, addressing heart issues from two angles, which is why there's significant interest in its potential to improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for preventing cardiotoxicity in HER2+ breast cancer patients?

Research has shown that carvedilol, which participants in this trial may receive, greatly lowers the chances of heart problems during cancer treatment. A study that combined results from multiple trials found it reduced the risk of noticeable heart issues by 58%. Empagliflozin, another treatment option in this trial, also shows promise for reducing heart-related problems, with evidence suggesting it can lower major heart incidents by 14-38%. Both treatments have successfully reduced the risk of heart failure. This trial will explore the potential benefits of using them together to protect the heart during breast cancer therapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Joshua Mitchell, M.D., MSCI, FAC, FICOS

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for breast cancer patients who are HER2 positive and starting HER2-directed therapy. It aims to prevent heart damage from these treatments. Participants should be willing to take either a beta blocker, an SGLT2 inhibitor, or both.

Inclusion Criteria

Systolic blood pressure ≥ 100 mmHg and resting heart rate ≥ 60 bpm

Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

My kidney function is above the minimum level required.

Exclusion Criteria

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry

I have had radiation therapy for mantle cell lymphoma.

I am allergic to medications similar to carvedilol or empagliflozin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carvedilol and/or empagliflozin for 12 weeks to assess feasibility and preliminary efficacy and safety

12 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carvedilol
• Empagliflozin

Trial Overview The study tests the safety and potential benefits of carvedilol (a beta blocker) and empagliflozin (an SGLT2 inhibitor), alone or together, in preventing heart issues during HER2-targeted breast cancer treatment.

How Is the Trial Designed?

Group I: Arm 3: Carvedilol BID + Empagliflozin QD Experimental Treatment 2 Interventions

Carvedilol by mouth twice per day (BID) for 12 weeks and empagliflozin by mouth daily (QD) for 12 weeks.

Group II: Arm 2: Empagliflozin QD Experimental Treatment 1 Intervention

Empagliflozin by mouth daily (QD) for 12 weeks.

Group III: Arm 1: Carvedilol BID Experimental Treatment 1 Intervention

Carvedilol by mouth twice per day (BID) for 12 weeks.

Group IV: Arm 4: Usual Care Active Control 1 Intervention

No medications.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

The EmDia trial is investigating the short-term effects of empagliflozin on left ventricular diastolic function in patients with type 2 diabetes, focusing on the E/E' ratio as a key measure over a 12-week period.

This study aims to provide insights into how empagliflozin may improve cardiovascular outcomes by assessing not only diastolic function but also other cardiovascular measures and molecular biomarkers, enhancing our understanding of its mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study. Jünger, C., Prochaska, JH., Gori, T., et al.[2023]

In a multicenter trial with 345 participants, carvedilol significantly improved left ventricular (LV) function and reduced mortality rates in patients with mild to moderate chronic heart failure, with a 73% lower risk of all-cause mortality compared to placebo.

Carvedilol also decreased hospitalization rates by 58% to 64% and was generally well tolerated, indicating its efficacy and safety as a treatment for chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Bristow, MR., Gilbert, EM., Abraham, WT., et al.[2022]

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]

In a study of 3730 patients with heart failure and reduced ejection fraction, empagliflozin significantly reduced the combined risk of death, hospitalization for heart failure, and urgent heart failure visits, showing benefits as early as 12 days after starting treatment.

Empagliflozin also led to fewer hospitalizations requiring intensive care and reduced the need for diuretic intensification, while improving patients' functional class, demonstrating its efficacy in managing worsening heart failure events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. Packer, M., Anker, SD., Butler, J., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0002870325000456

Effects of carvedilol on the prevention of cardiotoxicity ... In a prior meta-analysis of randomized trials, use of carvedilol was associated with 58% reduction in the odds of clinically overt cardiotoxicity.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006281/

Risk-guided cardioprotection with carvedilol in patients ... Carvedilol is part of guideline-directed medical therapy in heart failure with reduced ejection fraction and has been shown to reduce heart ...

3. jacc.org jacc.org/doi/10.1016/j.jacc.2018.02.049

Carvedilol for Prevention of Chemotherapy-Related ... This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04939883

NCT04939883 | Effects of Carvedilol on Cardiotoxicity in ... This is a multi-center, double-blind, randomized, placebo-controlled study that aims to establish the efficacy of carvedilol for the primary prevention of left ...

5. archivesofmedicalscience.com archivesofmedicalscience.com/Efficacy-and-harms-associated-with-beta-blockers-for-cardiotoxicity-in-cancer-patients,189501,0,2.html

Efficacy and harms associated with β-blockers for ... Our meta-analysis showed that β-blocker therapy did not improve most cardiac function outcomes related to anthracycline-related cardiotoxicity ...