Polypill for Heart Failure

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

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

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a single pill for low-income, racially diverse patients with heart failure. The pill combines several effective medications, making it easier for patients to take their treatment regularly. The goal is to improve heart function and reduce symptoms by simplifying the treatment process.

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.

What data supports the effectiveness of the Polypill drug for heart failure?

The research suggests that using multiple medications together, as in a Polypill, is recommended for heart failure with reduced ejection fraction (HFrEF) to improve outcomes. This approach aligns with guidelines that advocate for combining different drug classes to lower mortality in heart failure patients. ^{1 2 3 4 5}

Is the Polypill for Heart Failure safe for humans?

The safety of heart failure treatments, including those similar to the Polypill, has been studied, showing that while they can be effective, they may also cause adverse drug events (unwanted side effects) especially in older adults. It's important to monitor for these effects and consult with healthcare providers to ensure safe use. ^{3 6 7 8 9}

How is the Polypill drug different from other heart failure drugs?

The Polypill for heart failure is unique because it combines multiple medications into a single pill, potentially simplifying treatment by reducing the number of pills a patient needs to take daily. This approach may help ensure patients receive all recommended medications for heart failure with reduced ejection fraction (HFrEF) in one dose, addressing issues with medication adherence. ^{2 3 10 11 12}

Research Team

Eligibility Criteria

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.

I am 18 years old or older.

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).

Trial Timeline

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

Treatment Details

Interventions

• Control Rx (Drug)
• Polypill (Cardiovascular Agent)

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.

Participant Groups

Group I: Polypill Arm Experimental Treatment 1 Intervention

Patients 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). Three dose formulations of the pill, varied in metoprolol succinate dose, will be available for up-titration of the beta-blocker dose per ACC/AHA/HFSA guidelines.

Group II: Control Arm Active Control 1 Intervention

Patients will receive GDMT as usually prescribed by their provider. All of the individual components will be available at low- or no-cost to participants as individual pill formulations.

Polypill is already approved in India for the following indications:

Approved in India 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+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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 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]

References

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

Clinical Pharmacist's Intervention to Improve Medication Titration for Heart Failure: First Experience from Sudan. [2022]

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

Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study. [2023]

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

Polypharmacy in heart failure: drugs to use and avoid. [2014]

6. United States 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. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Adverse drug events and associated factors in heart failure therapy among the very elderly. [2021]

8. England 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Evolving therapies for the management of chronic and acute decompensated heart failure. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Medical therapy of heart failure with reduced ejection fraction: current evidence and new developments. [2018]

11. New Zealand 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. [2022]

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

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure. [2023]