Polypill Strategy for Heart Failure With Reduced Ejection Fraction

NCT04633005 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: UTexasSouthwestern
• Study Type: interventional
• Target: 212
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure with a reduced ejection fraction (HFrEF) represents a significant public health burden in the United States, with a growing prevalence particularly among African Americans and Hispanic Americans and individuals of low socioeconomic status (SES). Although effective therapies exist, gaps in their uptake contribute substantially to the excess burden of heart failure. The "polypill" is an inexpensive once daily pill containing three agents proven to improve morbidity and mortality in heart failure and represents potential strategy for increasing the utilization of proven HF therapies. The proposed study is a pragmatic, single-center, randomized trial to test the feasibility and effectiveness of a polypill-based strategy for the treatment of HFrEF in a low-income, racially diverse population.

Conditions

Heart Failure

Keywords

heart failure; adherence; LVEF; GDMT

Outcome Measures

Primary Outcomes (1)

• Left ventricular ejection fraction

  Measured by cardiac MR

  6 months

Secondary Outcomes (9)

• Hierarchical Composite Endpoint

  baseline through 6 months

• Kansas City Cardiomyopathy Questionnaire Quality of Life

  Baseline, 1 month, 3 months, 6 months

• Medication adherence

  6-months

• Six-minute walk distance

  baseline, 1 month, 3 months, 6 months

• LVEF through echocardiography

  6 months

Study Arms (2)

Polypill Arm

EXPERIMENTAL

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.

Drug: Polypill

Usual Care

ACTIVE COMPARATOR

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

Drug: Control Rx

Interventions

Polypill DRUG

Polypill formulation consisting of metoprolol succinate, empagliflozin, and spironolactone.

Polypill Arm

Control Rx DRUG

Typical prescriptions of guideline-directed therapies for heart failure with reduced ejection fraction.

Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults age \> = 18 years
• HF with left ventricular ejection fraction \<= 40% within 3 months of screening who are not on target dose guideline directed medical therapy
• New York Heart Association class II, III, or IV symptoms

You may not qualify if:

• Age \< 18
• Systolic blood pressure \< 110 mm Hg at enrollment if not on HTN therapy.
• Systolic blood pressure \<100 mm Hg at enrollment if on HTN therapy
• Serum creatinine \>2.5 for men and 2.0 for women
• Serum potassium \> 5.0 mEq/L
• Current need for inotropes
• Cardiac index \< 2.2 L/min/m2
• History of revascularization within 30 days or plan for revascularization
• History of type 1 diabetes mellitus
• History of allergic reaction or contraindication to a beta-blocker (BB), mineralocorticoid receptor antagonist (MRA), or sodium glucose cotransporter 2 inhibitor (SGLT2i)
• Contraindication to receive any of the components of the polypill
• Pregnancy
• \< 6 month expected survival
• Inability to provide written informed consent
• Persistent or permanent atrial fibrillation who may not have optimal MRI imaging

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75209, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Tin Fluorides

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Fluorides; Hydrofluoric Acid; Fluorine Compounds; Inorganic Chemicals; Tin Compounds; Cariostatic Agents; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 17, 2020
• Study Start: November 15, 2021
• Primary Completion: October 15, 2025
• Study Completion: October 31, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

US (1)