{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:30:29Z","timestamp":1790825429988,"version":"4.1.0"},"reference-count":17,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"unspecified","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["2020144"],"award-info":[{"award-number":["2020144"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R00HL157687"],"award-info":[{"award-number":["R00HL157687"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,30]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF) reduces morbidity and mortality and remains widely underused. An HFrEF polypill containing all four pillars of GDMT has been proposed as an implementation strategy to improve GDMT treatment rates and subsequent patient outcomes. We present the design and protocol for a proof-of-concept, pilot type I hybrid randomised clinical trial evaluating an HFrEF polypill compared with usual care among patients with HFrEF in Sri Lanka to evaluate short-term feasibility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This multi-centre, open-label, pilot type I hybrid randomised clinical trial will recruit 40 adults with HFrEF from two public hospital sites in Colombo, Sri Lanka. Participants will be randomised to an HFrEF polypill (containing bisoprolol, losartan, eplerenone, and dapagliflozin in three available strengths) or usual care and followed for 4 weeks. The primary outcome is feasibility of recruitment measured by recruitment rate and adherence to study protocols measured by completion rate of study-related procedures. Other key outcomes include adherence to GDMT and assessment of serious adverse events among other exploratory outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The study has been approved by the ethics review committee at the Faculty of Medicine, University of Kelaniya (Sri Lanka), the institutional review board at Washington University in St. Louis (United States), and the National Medicines Regulatory Authority (Sri Lanka). The findings of this pilot trial will inform the design and implementation of a future large-scale type I hybrid trial to assess the efficacy and safety of an HFrEF polypill in improving clinical outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration numbers<\/jats:title>\n                  <jats:p>Sri Lanka Clinical Trials Registry (SLCTR\/2024\/003); ClinicalTrials Registry (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06831864\">NCT06831864<\/jats:ext-link>).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-100952","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T04:17:25Z","timestamp":1754885845000},"page":"e100952","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Heart failure with reduced ejection fraction polypill implementation strategy in Sri Lanka: design and protocol of a pilot type I hybrid randomised clinical trial"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06831864","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-5601","authenticated-orcid":false,"given":"Anubha","family":"Agarwal","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asita","family":"de Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University of Kelaniya, Ragama, Western Province, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Institute for Informatics, Data Science, and Biostatistics, Washington University in St Louis School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumiyah","family":"Ajanthan","sequence":"additional","affiliation":[{"name":"RemediumOne, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Dahanayaka","sequence":"additional","affiliation":[{"name":"RemediumOne, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-3972","authenticated-orcid":false,"given":"Rupasvi","family":"Dhurjati","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health India, Hyderabad, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanaka","family":"Fernando","sequence":"additional","affiliation":[{"name":"RemediumOne, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamini","family":"Galappatthy","sequence":"additional","affiliation":[{"name":"National Hospital of Sri Lanka, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2682-7316","authenticated-orcid":false,"given":"Charles W","family":"Goss","sequence":"additional","affiliation":[{"name":"Institute for Informatics, Data Science, and Biostatistics, Washington University in St Louis School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Hively","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7071-2447","authenticated-orcid":false,"given":"Pathiyil B","family":"Jayagopal","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Lakshmi Hospital, Palakkad, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padinhare P","family":"Mohanan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Westfort Hi-Tech Hospital, Thrissur, Kerala, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka","family":"Patel","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3172-834X","authenticated-orcid":false,"given":"Dorairaj","family":"Prabhakaran","sequence":"additional","affiliation":[{"name":"Centre for Chronic Disease Control, New Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Rahuman","sequence":"additional","affiliation":[{"name":"Colombo South Teaching Hospital, Dehiwala, Western Province, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rodgers","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Roberts","sequence":"additional","affiliation":[{"name":"George Medicines, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyndavi","family":"Salwa","sequence":"additional","affiliation":[{"name":"Centre for Chronic Disease Control, New Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D","family":"Huffman","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA"},{"name":"The George Institute for Global Health, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5870-7936","authenticated-orcid":false,"given":"Abdul","family":"Salam","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health India, Hyderabad, Telangana, India"},{"name":"Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"2025071501552441000_15.7.e100952.1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac013"},{"key":"2025071501552441000_15.7.e100952.2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jacasi.2024.01.013","article-title":"Epidemiology and Burden of Heart Failure in 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Use of guideline-recommended heart failure drugs in high-, middle- and low-income countries: a systematic review and meta-analysis. 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