Heart Failure With Reduced Ejection FractionPhase 3NCT07569640
HFrEF Polypill in Sri Lanka RCT
A Phase 3 study testing HFrEF Polypill in people with Heart Failure With Reduced Ejection Fraction, run by Washington University School of Medicine at 12 sites in Sri Lanka.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- HFrEF Polypill
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,672 participants
- Where
- 12 sitesSri Lanka
- Study dates
- 17 Aug 2026to Apr 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Sri Lanka12 sites, 12 recruiting
- Not yet recruiting
Teaching Hospital Anuradhapura
Anuradhapura, North Central Province, 50000
Sumudu Wickramasinghe, MD MBBS, +94 77 298 7256, sumudusajeewaa84@gmail.com
- Recruiting
Rathnapura Teaching Hospital
Colombo, Ratnapura, 70000
Chinthaka Hathlahawatta, +94 718036938, chinthaka.hat@gmail.com
- Recruiting
National Hospital of Sri Lanka
Colombo, Western Province, 00100
Gamini Galappatthy, +94 112 691 111, gamini_galappatthy@hotmail.com
Thisal Semina
- Not yet recruiting
University Hospital - General Sir John Kotelawala Defence University
Colombo, Western Province, 10290
Namal Wijesinghe, +94 112044555, namal@remediumone.com
Subash Karunarathna
- Recruiting
Colombo South Teaching Hospital
Dehiwala, Western Province, 10350
M. B. F. Rahuman, +94 112 832 950, faslurcard@yahoo.com
Geethani Gunasekara
- Recruiting
National Hospital Galle
Galle, Southern Province, 80000
Sandamali Premaratne, +94 912 232 267, sandamali.premaratne@gmail.com
Piumi Rajawardhana
- Recruiting
Gampaha District General Hospital
Gampaha, Western Province, 11000
Suneth Karunarathne, 94 332 222 261, suneth87@gmail.com
- Recruiting
Teaching Hospital Jaffna
Jaffna, Northern Province, 40000
Poopalan Lakshman, +94 212 223 348, drplcc7@gmail.com
Thepana Sasiharan
- Recruiting
National Hospital Kandy
Kandy, Central Province, 20000
Gnanamoorthy Mayurathan, +94 812 222 261, gkmayurathan@yahoo.com
Zanoona Siddeek
- Recruiting
Teaching Hospital Kurunegala
Kurunegala, North Western Province, 60000
Thusitha Wijethunga, +94 372 222 261, tjwijethunga@gmail.com
Aruna Jayawarna
- Recruiting
District General Hospital Negombo
Negombo, Western Province, 11500
Ajith Wanniarachchi, +94 312 222 261, ajithwap@gmail.com
Anusha de Silva
- Recruiting
Colombo North Teaching Hospital
Ragama, Western Province, 11010
Sanjeewa Rajapakse, +94 11 2959261-4, sanjeewargs@yahoo.com
Thushari Gunawardana
About this study
Official title: Heart Failure With Reduced Ejection Fraction Polypill in Sri Lanka: A Multi-Center Type I Hybrid Randomized Controlled Trial
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:
Read more
- Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration
Secondary outcomes of the study:
- Rate of cardiovascular disease mortality over study duration
- Rate of recurrent heart failure hospitalizations over the study duration
- Rate of all-cause mortality over the study duration
- Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
- Change in BNP levels at 12 months and end of study
- 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)
- Change in physician-reported New York Heart Association class at 12-months and end of study
- 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:
- Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
- Proportion of participants with adverse events of special interest over study duration
- Proportion of participants with adverse events leading to HF drug discontinuation over study duration
- Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)
- 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.
- Being tested
- Usual Care, HFrEF Polypill
- Keywords
- HFrEF, Heart Failure, Heart Failure with Reduced Ejection Fraction, South Asia, Sri Lanka, Polypill, type I hybrid-effectiveness
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Usual CareOther
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 PolypillDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: HFrEF Polypill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
All-cause mortality is defined as death due to any cause.
Measured: 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
Measured: Baseline, 12 months, and at study completion, an average of 18 months.
Change in BNP levels at 12 months and end of study
Measured: Baseline, 12 months, and at study completion, an average of 18 months.
Change in overall and domain specific health-related quality of life at 12-months and end of study
Health-related quality of life (HRQoL) will be assessed by a translated validated Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23)
Measured: Baseline, 12 months, and at study completion, an average of 18 months.
Change in physician-reported New York Heart Association class at 12-months and end of study
Measured: Baseline, 12 months, and at study completion, an average of 18 months.
Adherence to guideline-directed medical therapy, persistence and dose optimization
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.
Measured: Baseline, 1, 6, 12 months, and at study completion, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2026
- Study start17 Aug 2026
- Primary completionApr 2029 (estimated)
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,672 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Chronic Disease Control, India, National Heart, Lung, and Blood Institute (NHLBI), RemediumOne (Pvt) Ltd., University of Kelaniya, The George Institute
- Responsible party
- Principal investigator, Anubha Agarwal, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07569640
- Sponsor's protocol ID
- 202605087
- Status last verified
- Aug 2026
- First submitted
- 11 Feb 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant-level data and accompanying data dictionaries will be made available to qualified investigators upon reasonable request and following approval by the Steering Committee, consistent with NIH data-sharing policies. Requests must include a methodologically sound proposal and a data use agreement ensuring participant confidentiality.