HFrEF Polypill in Sri Lanka RCT

NCT07569640 | Recruiting Phase 3 DMC

• 1 other identifier: 202605087
• Study Type: interventional
• Target: 1,672
• Locations: 1 country
• Sites: 11

Brief Summary

The aim of this study is to evaluate, in adults with HFrEF in Sri Lanka, the effects of an HFrEF polypill implementation strategy on the composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations, compared with usual care over a minimum of 12-months of follow-up. Primary outcome of the study: 1\) Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration Secondary outcomes of the study:

1. 1.Rate of cardiovascular disease mortality over study duration
2. 2.Rate of recurrent heart failure hospitalizations over the study duration
3. 3.Rate of all-cause mortality over the study duration
4. 4.Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
5. 5.Change in BNP levels at 12 months and end of study
6. 6.Change in overall and domain specific health-related quality of life at 12-months and end of study assessed by a translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23)
7. 7.Change in physician-reported New York Heart Association class at 12-months and end of study
8. 8.Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire at baseline, 1-, 6-, 12-months, and end of study. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study.
9. 9.Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
10. 10.Proportion of participants with adverse events of special interest over study duration
11. 11.Proportion of participants with adverse events leading to HF drug discontinuation over study duration
12. 12.Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)
13. 13.Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL)

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

HFrEF; Heart Failure; Heart Failure with Reduced Ejection Fraction; South Asia; Sri Lanka; Polypill; type I hybrid-effectiveness

Outcome Measures

Primary Outcomes (1)

• Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration

  Cardiovascular disease mortality is defined as death due to acute myocardial infarction, worsening heart failure, stroke, sudden cardiac death, arrhythmia, pulmonary embolism, cardiovascular procedures or their complications, other vascular causes, or any death of unknown cause unless a non-cardiovascular etiology is clearly established. HF hospitalization is defined as any unplanned hospitalization for at least 24 hours, for which the primary cause is 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 month, 6 month, 9 month, 12 month study visits, and every 3 months thereafter through study completion, an average of 18 months.

Secondary Outcomes (8)

• Rate of cardiovascular disease mortality over study duration

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

• Rate of recurrent heart failure hospitalizations over the study duration

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

• Rate of all-cause mortality over the study duration

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

• Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram

  Baseline, 12 months, and at study completion, an average of 18 months.

• Change in BNP levels at 12 months and end of study

  Baseline, 12 months, and at study completion, an average of 18 months.

Other Outcomes (5)

• Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration

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

• Proportion of participants with adverse events of special interest over study duration

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

• Proportion of participants with adverse events leading to HF drug discontinuation over study duration

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

Study Arms (2)

Usual Care

ACTIVE COMPARATOR

Participants in the comparator control group will receive usual care from their healthcare providers. Providers will be encouraged to treat all participants according to international and local clinical practice guidelines. Participants will receive their HFrEF medications through the pharmacy at the sites, where guideline-directed medical therapy are dispensed without charge to participants when available on the public hospital formulary.

Other: Usual Care

HFrEF Polypill

EXPERIMENTAL

The study intervention is a HFrEF polypill consisting of bisoprolol (beta-blocker), losartan (ARB), eplerenone (MRA), and dapagliflozin (SGLT2i) manufactured using the over-encapsulation method. There will be 3 strengths of the HFrEF polypill available: Strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 3: bisoprolol 10 mg + losartan 100 mg + eplerenone 50 mg + dapagliflozin 10 mg Every intervention participant will be established on the highest tolerated strength of the HFrEF polypill, with Strength 3 as the target dose. Following initiation at the strength matched to the participant's background guideline-directed medical therapy, the polypill strength will be advanced by one level at each scheduled study visit aligned with the initiation and titration protocol.

Drug: HFrEF Polypill

Interventions

HFrEF Polypill DRUG

The study intervention is a HFrEF polypill consisting of bisoprolol (beta-blocker), losartan (ARB), eplerenone (MRA), and dapagliflozin (SGLT2i) manufactured using the over-encapsulation method. There will be 3 strengths of the HFrEF polypill available: Strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 3: bisoprolol 10 mg + losartan 100 mg + eplerenone 50 mg + dapagliflozin 10 mg.

HFrEF Polypill

Usual Care OTHER

Participants in the comparator control group will receive usual care from their healthcare providers. Providers will be encouraged to treat all participants according to international and local clinical practice guidelines. Participants will receive their HFrEF medications through the pharmacy at the sites, where guideline-directed medical therapy are dispensed without charge to participants when available on the public hospital formulary.

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 (≥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 left ventricular 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 a highly 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 12 months.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Centre for Chronic Disease Control, India: collaborator
• RemediumOne: collaborator
• The George Institute: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Kelaniya: collaborator

Study Sites (11)

National Hospital Kandy

Kandy, Central Province, 20000, Sri Lanka

RECRUITING

Teaching Hospital Kurunegala

Kurunegala, North Western Province, 60000, Sri Lanka

NOT YET RECRUITING

Teaching Hospital Jaffna

Jaffna, Northern Province, 40000, Sri Lanka

RECRUITING

Rathnapura Teaching Hospital

Colombo, Ratnapura, 70000, Sri Lanka

NOT YET RECRUITING

National Hospital Galle

Galle, Southern Province, 80000, Sri Lanka

RECRUITING

National Hospital of Sri Lanka

Colombo, Western Province, 00100, Sri Lanka

NOT YET RECRUITING

University Hospital - General Sir John Kotelawala Defence University

Colombo, Western Province, 10290, Sri Lanka

NOT YET RECRUITING

Colombo South Teaching Hospital

Dehiwala, Western Province, 10350, Sri Lanka

RECRUITING

Gampaha District General Hospital

Gampaha, Western Province, 11000, Sri Lanka

NOT YET RECRUITING

District General Hospital Negombo

Negombo, Western Province, 11500, Sri Lanka

NOT YET RECRUITING

Colombo North Teaching Hospital

Ragama, Western Province, 11010, Sri Lanka

RECRUITING

Related Links

• Improving Care for Heart Failure With Reduced Ejection Fraction-A Potential Polypill-Based Strategy

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Anubha Agarwal, MD MSc

CONTACT

+1 314-362-1291; anubha@wustl.edu

Asita de Silva, MBBS DPhil FRCP

CONTACT

+94 11 2961241; asita@kln.ac.lk

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: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: May 6, 2026
• Study Start: August 17, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: De-identified individual participant data will become available after publication of the primary results manuscript and remain available thereafter, subject to Steering Committee approval of each request.
• Access Criteria: Qualified investigators may request access by submitting a methodologically sound proposal to the study Steering Committee. Approved requests require a signed data use agreement ensuring participant confidentiality, consistent with NIH data-sharing policies.

Locations

SR (11)