NCT07569640

Brief Summary

Primary Outcome: Composite of cardiovascular death or recurrent heart failure hospitalization over study duration Secondary Outcomes: Cardiovascular death over study duration Recurrent heart failure hospitalizations over study duration All-cause mortality over study duration Change in left ventricular ejection fraction from baseline to 12 months by echocardiogram. Change in natriuretic peptide levels from baseline to 12 months. Change in health-related quality of life from baseline to 12 months using the Kansas City Cardiomyopathy Questionnaire. Change in New York Heart Association functional class from baseline to 12 months. Adherence to heart failure medications assessed by pill count and questionnaire, medication persistence assessed as continuation of assigned therapy after initiation, and dose optimization assessed as proportion achieving final/target doses over study duration Safety Outcomes: Proportion of participants with serious adverse events or sudden unexpected serious adverse reaction over study duration Proportion with adverse events of special interest (symptomatic hypotension, diabetic ketoacidosis, severe hypoglycemia, lower limb amputation, hyperkalemia, or worsening kidney function) over study duration Proportion of participants who stop study drug because of adverse events over study duration Change in serum potassium over study duration Change in serum creatinine over study duration Participants will be randomly assigned to one of two groups, intervention or usual care. The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options (at the discretion of their treating physician). Both groups will be observed over a minimum of 12-months of follow-up to assess their medication adherence, clinical symptoms, laboratory measures, health related quality of life, and need for medication adjustment amongst other measures.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,656

participants targeted

Target at P75+ for phase_3

Timeline
33mo left

Started Jun 2026

Typical duration for phase_3

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 11, 2026

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 6, 2026

Completed
26 days until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2028

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2029

Last Updated

May 6, 2026

Status Verified

May 1, 2026

Enrollment Period

2.5 years

First QC Date

February 11, 2026

Last Update Submit

May 1, 2026

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

HFrEFHeart FailureHeart Failure with Reduced Ejection FractionSouth AsiaSri LankaPolypill

Outcome Measures

Primary Outcomes (1)

  • Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations

    Cardiovascular disease mortality is defined as death due to acute myocardial infarction, worsening heart failure, stroke, sudden cardiac death, arrhythmia, pulmonary embolism, cardiovascular procedures, vascular causes, or any death of unknown cause unless a non-cardiovascular etiology is clearly established. Recurrent HF hospitalizations is defined as any hospitalization in which the primary cause is worsening heart failure, accompanied by objective evidence of decompensation and requiring initiation or intensification of HF-specific therapy, occurring after a documented period of clinical stability of at least 12 hours since the prior HF event. Adjudicated by the blinded Outcome Adjudication Committee.

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

Secondary Outcomes (11)

  • Rate of cardiovascular disease mortality

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • Rate of recurrent heart failure hospitalizations

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • Rate of all-cause mortality

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • Change in left ventricular ejection fraction

    Baseline, 12 months

  • Natriuretic peptide levels change

    Baseline, 12 months

  • +6 more secondary outcomes

Other Outcomes (5)

  • Serious adverse events or sudden unexpected serious adverse reaction

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • Adverse Events of Special Interest

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • Adverse events leading to study drug discontinuation

    1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

  • +2 more other outcomes

Study Arms (2)

Control arm

ACTIVE COMPARATOR

Participants in the comparator control arm will receive usual care, as per their physician's discretion.

Other: Comparator Arm

Study Intervention arm

EXPERIMENTAL

Participants in the intervention group will be provided the HFrEF polypill by the study.

Drug: HFrEF Polypill

Interventions

Comparator ArmOTHER

Participants in the comparator control group will receive usual care by their healthcare providers. Providers will be encouraged to treat all participants according to international and local clinical practice guidelines.

Control arm
HFrEF PolypillDRUG

The heart failure with reduced ejection fraction (HFrEF) polypill will include 4 guideline recommended medications used to treat HFrEF patients. The dose of initiation and titration will be at the investigator's discretion. HFrEF polypill strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg; HFrEF polypill strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg; HFrEF polypill strength 3: bisoprolol 10 mg + losartan 100 + eplerenone 50 mg + dapagliflozin 10 mg

Study Intervention arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adults (≥18 years old)
  • Diagnosis of heart failure with reduced ejection fraction (HFrEF) including clinical symptoms or clinical signs or natriuretic peptide elevation AND echocardiographic or other evidence of reduced ejection fraction (EF≤40%)
  • New York Heart Association Class II, III, or IV symptoms

You may not qualify if:

  • Known contraindication to any of the HFrEF polypill components (e.g., advanced renal disease, bradycardia, allergy, amongst others).
  • Significant renal impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m2)
  • Raised serum potassium \>5 mEq/L.
  • Symptomatic hypotension or systolic BP \<100 mmHg as per the average of last 2 of the 3 measurements at visit 1.
  • Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
  • History of type 1 diabetes mellitus.
  • Women who are pregnant, breastfeeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).
  • Concomitant illness, physical impairment or mental condition which in the opinion of the study team/ primary physician could interfere with the conduct of the study including outcome assessment.
  • Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
  • Participant's responsible physician believes it is not appropriate for participant to participate in the study.
  • Inability or unwillingness to provide written informed consent.
  • Involvement in the planning and/or conduct of the study.
  • Unable to complete study procedures and/or plan to move out of the study site area in the next 2 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Central Study Contacts

Anubha Agarwal, MD MSc

CONTACT

314-362-1291anubha@wustl.edu

Adam Hively, MPH

CONTACT

adamh@wustl.edu

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 11, 2026

First Posted

May 6, 2026

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

March 1, 2029

Last Updated

May 6, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will not share

When the study is over, research findings will be available at www.ClinicalTrials.gov and Sri Lanka Clinical Trials Registry. Laboratory results will be shared with participants and their health care providers. The research findings will also be published in the form of research articles or presented at scientific meetings.