Delivering guideline-directed medical therapy for heart failure with reduced ejection fraction as an over-encapsulated polypill: rationale and protocol for the COMBO-HF-X pilot crossover randomised clinical trial
Year: 2025
Type: article
Study design: Study Protocol
Abstract: INTRODUCTION: A four-drug regimen of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is underused, in part due to prescriber inertia and low patient adherence. Although fixed-dose combination pills ('polypills') have improved adherence and clinical outcomes for other conditions, there are no polypills available that combine multiple classes of GDMT for HFrEF. Pharmacy-level over-encapsulation, in which several tablets are combined into one capsule, offers an opportunity to create customised HFrEF polypills with the goal of improving delivery of HFrEF therapies. METHODS AND ANALYSIS: In the COMBO-HF-X pilot crossover randomised clinical trial, we will enrol 30-40 patients with HFrEF in a safety-net public healthcare system in San Francisco, California. Participants will be randomised 1:1 to receive GDMT as individual tablets or as a customised, over-encapsulated HFrEF polypill. After 1 month, participants will cross over to the other formulation (individual tablets or a HFrEF polypill). Participants will attend in-person visits at 0, 4 and 8 weeks. GDMT will be initiated and titrated by study physicians as clinically indicated in accordance with HFrEF treatment guidelines. The primary outcome will be adherence to GDMT by pill count. Key feasibility outcomes will include the successful recruitment of 30-40 participants and completion of study procedures for at least 20 participants. Implementation outcomes will include the cost and time required for HFrEF polypill preparation, which will be performed by a community pharmacy partner. Exploratory clinical outcomes will include change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and Kansas City Cardiomyopathy Questionnaire. Acceptability will be assessed through a patient exit survey and semistructured exit interviews with patients, their primary care and cardiology providers, and pharmacy staff. ETHICS AND DISSEMINATION: Study findings will be published in peer-reviewed journals. The protocol of this study was approved by the Institutional Review Board of the University of California, San Francisco. Written informed consent for COMBO-HF-X was obtained from all participants. TRIAL REGISTRATION NUMBER: NCT06029712.
Source: BMJ Open
Authors: Colette DeJong, Matthew S Durstenfeld, Jonathan D Davis, Christina S Wang, Elise D Riley, Mark D Huffman, Matthew D Hickey, Starley B Shade, Justin C Chen, Dhruv S Kazi, Janet Grochowski, Wayne T Steward, Lucas S Zier, Niloufar Moreau, Alexander T Sandhu, Paul A Heidenreich, Anubha Agarwal, Priscilla Y Hsue
Institutions: VA Palo Alto Health Care System, Stanford Medicine, Stanford University, San Francisco General Hospital, University of California, San Francisco, Washington University in St. Louis, The George Institute for Global Health, Beth Israel Deaconess Medical Center, Harvard University, University of California, Los Angeles
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,839
Funders: Doris Duke Charitable Foundation, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G2618753827, Role of Hematopoietic System and Proteomics in HIV-Associated CardiovascularDisease, G3449348415, G4674129376, G5372683015, G5833008556, G6245908341, G7120641930, G81379742, Vocal Communication and Behavior, G9000323077, Implementation Strategies to Improve Hypertension Treatment in Kenya, Center for AIDS Prevention Studies (CAPS), Mentoring patient-oriented research on the health consequences of polydrug use, Heart Failure Polypill in India: A Late-Stage Implementation Strategy, Clinical and Translational Science Institute
OpenAlex ID: W4408745475