Polypill for Heart Failure

(POLY-HF Trial)

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Beta-blockers, MRAs, SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Pregnancy, Extreme obesity, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a once-daily "polypill" designed for people with heart failure who have a reduced ejection fraction, meaning the heart does not pump blood effectively. The polypill combines three medications that have improved outcomes in heart failure. The study will compare this pill to usual care to determine if it simplifies and enhances heart failure treatment, particularly for low-income, racially diverse groups. Suitable participants have heart failure symptoms and reduced heart function but are not yet on the optimal dose of current treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important heart failure research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, it mentions that participants should not be on optimal guideline-directed medical therapy, which might imply some changes to your current treatment. It's best to discuss this with the trial coordinators.

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

Research has shown that the polypill, which combines metoprolol succinate, empagliflozin, and spironolactone, has been studied for treating heart failure with reduced ejection fraction (HFrEF). Past studies have tested these medicines individually, demonstrating their effectiveness in managing heart failure.

Metoprolol succinate, a beta-blocker, reduces the heart's workload. Empagliflozin helps the body eliminate excess sugar and salt through urine. Spironolactone aids in removing extra fluid. Each drug has been used in heart failure treatment and is generally well-tolerated on its own.

The polypill combines these three medicines into one daily pill. Although the combination remains under study, each drug has received FDA approval for other uses, indicating relative safety. However, monitoring for any new side effects when these drugs are combined is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for heart failure, which often involves managing multiple separate medications, the polypill offers a convenient all-in-one solution. This polypill combines three powerful agents: metoprolol succinate (a beta-blocker), empagliflozin (an SGLT2 inhibitor), and spironolactone (a mineralocorticoid antagonist). Researchers are excited because this single pill simplifies treatment by reducing the number of medications patients need to take, potentially improving adherence and outcomes. Additionally, the polypill's ability to offer adjustable doses of metoprolol succinate allows for personalized treatment adjustments according to clinical guidelines, making it a versatile option for managing heart failure.

What evidence suggests that the polypill might be an effective treatment for heart failure?

Research has shown that a new pill, the polypill, which combines three medications, may help treat heart failure with reduced ejection fraction (HFrEF). This trial will test the polypill, which includes metoprolol succinate, empagliflozin, and spironolactone, as part of one treatment arm. These drugs are known to improve heart function and lower the risk of heart problems. Studies on each of these medications have demonstrated improvements in heart health and a reduced risk of death in heart failure patients. By combining them into one pill, the goal is to simplify treatment adherence and enhance outcomes. Early signs suggest this approach could help more people benefit from proven heart failure treatments. Participants in the other arm will receive usual care with individual components of guideline-directed medical therapy. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with heart failure and a reduced ejection fraction (HFrEF), specifically those not already on the best standard treatments. It's aimed at helping low-income, racially diverse populations. People can't join if they're pregnant, have severe blood pressure issues, recent revascularization, type 1 diabetes, allergies to certain heart medications, extremely high creatinine or potassium levels in their blood, need for constant heart support drugs, very low cardiac output or are severely obese.

Inclusion Criteria

I have moderate to severe heart condition symptoms.

My heart's pumping ability is reduced and I'm not on the best treatment plan yet.

Exclusion Criteria

Pregnancy

My blood pressure is below 110 mm Hg and I'm not on blood pressure medication.

My kidney function test shows creatinine above 2.5 (men) or 2.0 (women).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a polypill-based strategy for the treatment of HFrEF, with follow-up visits to assess medication adherence and health status

12 months

Monthly follow-up visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of LVEF and NT-proBNP levels

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Control Rx
• Polypill

Trial Overview

The study is testing a 'polypill'—a single pill containing three medications that improve outcomes in heart failure patients—against usual care without the polypill. The goal is to see if this approach works well in a practical setting among people of different races and lower socioeconomic status.

How Is the Trial Designed?

Group I: Polypill Arm Experimental Treatment 1 Intervention

Participants will be randomized to receiving a fixed-dose polypill in addition to other guideline-directed medical therapies prescribed by their physician. Polypill formulations will include metoprolol succinate (a beta-blocker), empagliflozin (an SGLT2-inhibitor), and spironolactone (a mineralocorticoid antagonist). Four dose formulations of the pill, varied in metoprolol succinate dose (25, 50, 100, 150 mg), will be available for up-titration of the beta-blocker dose per ACC/AHA/HFSA guidelines.

Group II: Usual Care Active Control 1 Intervention

Participants in the usual care arm received individual components of GDMT with initiation and up-titration performed in partnership with their primary outpatient physician teams

Polypill is already approved in India, United States for the following indications:

Approved in India as HFrEF Polypill for:

• Heart failure with reduced ejection fraction

Approved in United States as HFrEF Polypill for:

• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

A comprehensive analysis of 69 randomized controlled trials involving 91,741 subjects showed that combination therapies for chronic heart failure with reduced ejection fraction (HFrEF) significantly reduce the risk of all-cause mortality, with the most effective combinations including beta blockers, ACE inhibitors, and newer drugs like SGLT2 inhibitors and ARNI.

The combination of SGLT2 inhibitors with ARNI, beta blockers, and mineralocorticoid receptor antagonists resulted in the lowest risk of death (hazard ratio of 0.28), indicating that multi-drug regimens can greatly improve outcomes for patients with HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network meta-analysis of medical therapy efficacy in more than 90,000 patients with heart failure and reduced ejection fraction. De Marzo, V., Savarese, G., Tricarico, L., et al.[2022]

Sacubitril-valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations related to heart failure, highlighting its efficacy as a new treatment option.

Other emerging therapies like ivabradine and ferric carboxymaltose have also proven effective in reducing hospitalizations for heart failure, indicating a promising expansion of treatment options for managing chronic heart failure and acute decompensated heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving therapies for the management of chronic and acute decompensated heart failure. Cook, JC., Tran, RH., Patterson, JH., et al.[2021]

In a study of 259 patients with advanced heart failure, those hospitalized reported significantly higher symptom burden and psychosocial distress compared to outpatients, indicating a need for better management of these issues.

A high percentage of patients (82% hospitalized and 52% outpatients) met criteria for specialized palliative care support, highlighting the importance of addressing palliative needs even in patients with a relatively good prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study. Strangl, F., Ischanow, E., Ullrich, A., et al.[2023]

In a study of 3,518 outpatients with heart failure and reduced ejection fraction (HFrEF), significant gaps were found in the prescription and dosing of recommended medications, with 27% not receiving ACEI/ARB/ARNI, 33% not on beta-blockers, and 67% not on MRAs.

Only 1% of patients eligible for all medication classes were receiving target doses of ACEI/ARB/ARNI, beta-blockers, and MRAs simultaneously, highlighting the need for improved strategies to ensure guideline-directed medical therapy is utilized effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. Greene, SJ., Butler, J., Albert, NM., et al.[2022]

In 2020, 99.1% of Medicare prescription drug plans required high cost sharing for angiotensin receptor-neprilysin inhibitors (ARNI) and 98.5% for sodium-glucose cotransporter-2 inhibitors (SGLT2i), making quadruple therapy for heart failure potentially unaffordable for many patients.

The median out-of-pocket cost for a 30-day supply of quadruple therapy was $94, significantly higher than the $3 median cost for generic regimens, highlighting the financial burden on Medicare patients with heart failure with reduced ejection fraction (HFrEF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure. Faridi, KF., Dayoub, EJ., Ross, JS., et al.[2023]

Patients with heart failure (HF), particularly those with reduced ejection fraction (HFrEF), often face polypharmacy, meaning they take four or more medications, which complicates their treatment due to the presence of multiple comorbidities.

The paper provides strategies for effectively combining evidence-based therapies for HFrEF and managing common comorbidities, while also highlighting specific prescription and nonprescription medications that should be avoided or used cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polypharmacy in heart failure: drugs to use and avoid. Reed, BN., Rodgers, JE., Sueta, CA.[2014]

The 2021 European Society of Cardiology guidelines emphasize the importance of early treatment with all four key drug classes for heart failure with reduced ejection fraction (HFrEF), which include ACE inhibitors, ARNI, beta-blockers, MRAs, and SGLT2 inhibitors.

This article serves as a practical guide for physicians to ensure safe and effective management of HFrEF, highlighting the need for comprehensive treatment strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. Soltani, S., Böhm, M., Frey, N., et al.[2022]

In a study of 138 stable outpatients aged over 70 with heart failure, higher doses of ACE inhibitors/angiotensin receptor blockers (ACEIs/ARBs) were linked to improved long-term survival, with a significant hazard ratio of 0.67 for the total population.

Both low and high doses of ACEIs/ARBs significantly enhanced survival compared to no treatment, and high doses were particularly effective, showing a hazard ratio of 0.13, indicating a strong benefit for older patients with reduced ejection fraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure. Sargento, L., Simões, AV., Longo, S., et al.[2022]

In the DAPA-HF trial involving 4742 patients with heart failure and reduced ejection fraction (HFrEF), dapagliflozin significantly reduced the risk of cardiovascular death or worsening heart failure, regardless of baseline kidney function, indicating its efficacy across different eGFR levels.

Dapagliflozin also slowed the decline in kidney function over time, with a significantly less rate of eGFR decline compared to placebo, demonstrating its potential renal protective effects even in patients without diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. Jhund, PS., Solomon, SD., Docherty, KF., et al.[2021]

Adverse drug events (ADEs) are common in older adults (over 75 years) receiving heart failure therapy, with 57% of studies reporting such events, particularly with beta blockers and spironolactone.

Factors like advanced age, poor left ventricular function, and higher New York Heart Association Class are associated with increased ADEs, indicating a need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug events and associated factors in heart failure therapy among the very elderly. Sztramko, R., Chau, V., Wong, R.[2021]

Recent advancements in medical therapies for heart failure with reduced ejection fraction (HFrEF) have significantly decreased both morbidity and mortality, transforming it from a palliative condition to a manageable one.

The primary treatment strategy involves blocking the renin-angiotensin-aldosterone and β-adrenergic systems, with new therapies on the horizon, such as dual angiotensin receptor and neprilysin inhibition, promising further improvements in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical therapy of heart failure with reduced ejection fraction: current evidence and new developments. Naegele, M., Flammer, AJ., Enseleit, F., et al.[2018]

In a study of 110 patients with heart failure and reduced ejection fraction (HFrEF), the inclusion of clinical pharmacists in the healthcare team significantly increased the percentage of patients reaching target doses of key medications, such as ACE inhibitors and beta blockers, from 0% to 77.4% and from 8.6% to 66.1%, respectively.

The up-titration of these medications led to notable improvements in clinical outcomes, including better ejection fraction and enhanced scores on the New York Heart Association (NYHA) scale, demonstrating the effectiveness of pharmacist interventions in managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacist's Intervention to Improve Medication Titration for Heart Failure: First Experience from Sudan. Ahmed, KO., Taj Eldin, I., Yousif, M., et al.[2022]

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Study Overview. Brief Summary. Heart failure with a reduced ejection fraction (HFrEF) represents a significant public health burden in the United States ...