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NCT Number: NCT07569640

HFrEF Polypill in Sri Lanka RCT

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.

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Key information

Conditions

Heart Failure With Reduced Ejection Fraction Cardiovascular Diseases Heart Diseases Heart Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

National Hospital Kandy, Kandy, Central Province, Sri Lanka

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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.

Treatment and study plan

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.

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.

Primary outcomes

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

    Time frame: 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.

    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.

Secondary outcomes

  1. Rate of cardiovascular disease mortality over study duration

    Time frame: 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.

    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.

    Adjudicated by the blinded Outcome Adjudication Committee.

  2. Rate of recurrent heart failure hospitalizations over the study duration

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

    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.

  3. Rate of all-cause mortality over the study duration

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

    All-cause mortality is defined as death due to any cause.

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

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

  5. Change in BNP levels at 12 months and end of study

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

  6. Change in overall and domain specific health-related quality of life at 12-months and end of study

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

    Health-related quality of life (HRQoL) will be assessed by a translated validated Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23)

  7. Change in physician-reported New York Heart Association class at 12-months and end of study

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

  8. Adherence to guideline-directed medical therapy, persistence and dose optimization

    Time frame: Baseline, 1, 6, 12 months, and at study completion, an average of 18 months

    Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire.

    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.

Other outcomes

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

    Time frame: 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 serious adverse events according to Good Clinical Practice (GCP) guidelines (ICH E6 [R3]) over the study duration.

  2. Proportion of participants with adverse events of special interest over study duration

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

    Adverse events of special interest:

    • symptomatic hypotension
    • diabetic ketoacidosis
    • severe hypoglycemia
    • lower limb amputation
    • hyperkalemia
    • worsening renal function
    • falls

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

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

  4. Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)

    Time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.

  5. Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL)

    Time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.

Study contacts

Contact information is provided by the study sponsor or research team.

Anubha Agarwal, MD MSc

CONTACT

[email protected]

+1 314-362-1291

Asita de Silva, MBBS DPhil FRCP

CONTACT

[email protected]

+94 11 2961241

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • Centre for Chronic Disease Control, India
  • National Heart, Lung, and Blood Institute (NHLBI)
  • RemediumOne
  • The George Institute
  • University of Kelaniya

Registry information

Official study title

Heart Failure With Reduced Ejection Fraction Polypill in Sri Lanka: A Multi-Center Type I Hybrid Randomized Controlled Trial

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
May 6, 2026
Registry last updated
Aug 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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