HFrEF Polypill in Sri Lanka RCT

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. Rate of cardiovascular disease mortality over study duration
2. Rate of recurrent heart failure hospitalizations over the study duration
3. Rate of all-cause mortality over the study duration
4. Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
5. Change in BNP levels at 12 months and end of study
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. Change in physician-reported New York Heart Association class at 12-months and end of study
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.

Safety outcomes:

1. Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
2. Proportion of participants with adverse events of special interest over study duration
3. Proportion of participants with adverse events leading to HF drug discontinuation over study duration
4. Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)
5. Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL)

Participants will be randomly assigned 1:1 stratified by sex and site to one of two groups, intervention (experimental arm) or usual care (control arm). 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. Both groups will be observed over a minimum of 12-months of follow-up to assess key outcomes.

Conditions

• Heart Failure With Reduced Ejection Fraction

Interventions

OTHER

Usual Care

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.

DRUG

HFrEF Polypill

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.

Sponsors & Collaborators

• Centre for Chronic Disease Control, India

  collaborator OTHER

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• RemediumOne

  collaborator UNKNOWN

• University of Kelaniya

  collaborator OTHER

• The George Institute

  collaborator OTHER

• Washington University School of Medicine

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-17

Primary Completion

2029-04-30

Completion

2029-04-30

Countries

• Sri Lanka

Study Locations