Polypill for Cardiomyopathy Prevention in Type 2 Diabetes

(PolyPreventHF Trial)

Overseen By Ambarish Pandey, MD, MSCS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Congestive heart failure, Hyperkalemia, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new polypill (a combination pill) for individuals with type 2 diabetes at high risk of heart failure. The polypill combines three medications designed to improve heart health and simplify adherence to treatment. Participants will either take the polypill or the same medications separately to determine which method is more effective. This trial suits those with type 2 diabetes and chronic kidney issues who have not yet experienced heart failure. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, since the study involves a polypill therapy, it's possible that adjustments to your current medications might be needed. Please consult with the trial coordinators for specific guidance.

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

Research shows that the ingredients in the polypill, such as empagliflozin, losartan, and finerenone, have undergone previous study. Empagliflozin and losartan treat heart and kidney health issues, and people generally tolerate them well.

Studies on finerenone, such as the FIGARO-DKD trial, found it can lower the risk of heart failure in people with chronic kidney disease and type 2 diabetes. Some participants in these studies experienced side effects, but they were usually mild.

While the polypill combines these drugs, early research and the history of its ingredients suggest it is generally safe. However, since this trial is in the early stages, unknowns may still exist. It's always important to consult a doctor about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the polypill for cardiomyopathy prevention in type 2 diabetes because it combines three medications—finerenone, empagliflozin, and losartan—into one daily pill. This is unique because it simplifies treatment by bundling a diuretic, a heart protective agent, and a kidney protective agent into a single dose, potentially improving adherence compared to taking multiple separate medications. Unlike standard treatments that typically involve taking each of these drugs individually, this polypill approach could streamline medication regimens and enhance the protective effects against heart and kidney complications in diabetics. Moreover, by targeting multiple pathways at once, this polypill might offer broader protection and better outcomes for patients.

What evidence suggests that this polypill is effective for preventing heart failure in type 2 diabetes?

Research shows that each component of the polypill—empagliflozin, losartan, and finerenone—benefits heart health, particularly for individuals with type 2 diabetes. Studies have found that empagliflozin, which aids the kidneys in removing sugar from the body, can lower the risk of heart failure. Losartan, a drug that relaxes blood vessels, effectively controls high blood pressure, a risk factor for heart failure. Finerenone has reduced the risk of heart failure in those with chronic kidney disease and type 2 diabetes.

In this trial, participants will receive either the polypill, which combines these medications, or a combined prescription of the individual medications (SGLT2i, ARB, or finerenone). A review of multiple studies suggests that using a polypill can improve heart health compared to standard treatments. These findings indicate that the polypill could help prevent heart problems in people with type 2 diabetes. ^{1 3 6 7 8}

Who Is on the Research Team?

Ambarish Pandey, MD

Principal Investigator

UT Southwestern

Are You a Good Fit for This Trial?

This trial is for people with type 2 diabetes who are at high risk of heart failure. They should have a certain level of kidney function and protein in their urine, but not be on dialysis or have severe kidney disease. Pregnant individuals, those unable to exercise for tests, or with very high potassium levels can't join.

Inclusion Criteria

I have Type 2 diabetes, moderate kidney issues, and a high risk of heart failure.

Exclusion Criteria

I have been diagnosed with congestive heart failure.

I am allergic or react badly to one of the ingredients in the polypill.

Your blood has too much potassium, above the level of 5.0.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either polypill therapy or usual care for 6 months

6 months

Visits at baseline, 1 month, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Polypill

Trial Overview

The study is testing a polypill combining three medications (empagliflozin, losartan, finerenone) against usual care over three months. It aims to see if the pill helps patients stick to their treatment better and improves oxygen use during peak exercise.

How Is the Trial Designed?

Group I: Polypill Experimental Treatment 1 Intervention

Participants will take a polypill containing finerenone 10 mg, empagliflozin 12.5 mg, and losartan (25, 50 mg, or 100 mg) daily.

Group II: Combined prescription of the individual medications Active Control 1 Intervention

Participants will be initiated on an SGLT2i, ARB, or finerenone if they are not already on the medication class.

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

People with type 2 diabetes have a higher risk of heart failure (HF) and worse outcomes compared to non-diabetics, primarily due to factors like ischemic heart disease and diabetic cardiomyopathy.

While treatments like angiotensin-converting enzyme inhibitors and β-blockers can improve heart function in heart failure with reduced ejection fraction (HFrEF), managing underlying risk factors is crucial for heart failure with preserved ejection fraction (HFpEF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Bell, DSH., Goncalves, E.[2020]

In the DAPA-HF trial, dapagliflozin significantly reduced the risk of worsening heart failure episodes and cardiovascular death, with a 36% lower incidence in patients taking dapagliflozin compared to placebo over a median follow-up of 18.2 months.

Outpatient worsening of heart failure was common and associated with a higher risk of death, but dapagliflozin effectively lowered these events, demonstrating its efficacy in managing heart failure alongside standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. Docherty, KF., Jhund, PS., Anand, I., et al.[2021]

In the DAPA-HF trial involving 4744 patients with heart failure and reduced ejection fraction, dapagliflozin significantly reduced the risk of worsening heart failure and cardiovascular death in both ischaemic and non-ischaemic patients, demonstrating its efficacy across different aetiologies.

Dapagliflozin was found to be safe and well-tolerated, with similar rates of serious adverse events and treatment discontinuation compared to placebo, indicating it can be a reliable treatment option for heart failure patients regardless of the underlying cause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial. Butt, JH., Nicolau, JC., Verma, S., et al.[2021]

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]

Diabetes and heart failure (HF) often co-occur, complicating treatment and leading to worse outcomes, highlighting the need for integrated management strategies.

Emerging evidence suggests that diabetes medications can not only help manage diabetes but also reduce heart failure events, even in patients without diabetes, indicating their potential dual benefit in treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Management in Patients with Heart Failure. Shen, J., Greenberg, BH.[2021]

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]

Beta-blockers, antialdosterone agents, and combined ARB/neprilysin inhibitors are effective in preventing sudden cardiac death (SCD) and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), based on a review of 41 systematic reviews.

Angiotensin-converting enzyme inhibitors (ACE-i) significantly reduce all-cause mortality but do not prevent SCD, indicating that alternative strategies may be needed for patients at high risk of SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of drug interventions to prevent sudden cardiac death in patients with heart failure and reduced ejection fraction: an overview of systematic reviews. Al-Gobari, M., Al-Aqeel, S., Gueyffier, F., et al.[2021]

Heart failure is common in patients with type 2 diabetes and significantly worsens their prognosis, leading to higher rates of hospitalization and mortality.

The article reviews how different antidiabetic medications can impact the incidence and outcomes of heart failure in these patients, highlighting the importance of medication choice in managing both diabetes and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart failure: an underestimated therapeutic target in diabetes. Marx, N.[2020]

The patient with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF) showed significant improvement in diastolic function and exercise capacity after three weeks of low-carbohydrate nutrition and moderate exercise, highlighting the potential efficacy of metabolic interventions in managing HFpEF.

This case suggests that HFpEF related to insulin resistance is often overlooked in obese patients, and that traditional low-fat dietary recommendations may worsen their condition; instead, a low-carbohydrate diet can effectively reverse insulin resistance and improve cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diastolic heart failure treated by diet]. Heilmeyer, P., von Bibra, H.[2016]

Sodium glucose transporter-2 inhibitors (SGLT-2i) significantly reduce heart failure events and hospitalizations in patients with type 2 diabetes, as shown in large-scale randomized controlled trials like EMPA-REG OUTCOME and CANVAS.

In contrast to other diabetes medications such as DPP-IV inhibitors and thiazolidinediones, which have shown neutral or negative effects on heart failure, SGLT-2i therapy is effective in preventing heart failure in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications. Bassi, N., Fonarow, GC.[2019]

Heart failure (HF) is a significant concern for individuals with diabetes, often linked to conditions like ischaemia and hypertension, but diabetic cardiomyopathy is increasingly recognized as a direct cause of HF.

New glucose-lowering medications are now routinely evaluated for their cardiovascular effects, providing valuable insights into their safety and risks for patients with existing heart failure, which is crucial for developing effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical aspects of heart failure in individuals with diabetes. Bowes, CD., Lien, LF., Butler, J.[2020]

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