Rationale and design of Dapagliflozin vErsus SacubiTrIl-valsartaN therapY in Heart Failure with reduced ejection fraction (DESTINY-HF): a pragmatic randomised controlled trial protocol

BACKGROUND: Heart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) are in the first line for HFrEF, but no head-to-head trials are available. Moreover, growth differentiation factor-15 (GDF-15) has been demonstrated as a promising prognostic marker, specifically for HFrEF, but has not been explored much. METHODS: This pragmatic randomised controlled trial recruits 100 patients with HFrEF (ejection fraction <40%) of New York Heart Association (NYHA) II-III and allocates them in a 1:1 ratio to the dapagliflozin and sacubitril/valsartan groups. The primary objective is to assess the difference in N-terminal pro-brain natriuretic peptide serum levels at the end of 16 weeks. The secondary efficacy objectives are to assess GDF-15, Kansas City Cardiomyopathy Questionnaire-overall summary score and estimated glomerular filtration rate. Patients will be assessed at baseline, fourth week and 16th week after randomisation. As health technology assessment practices widely differ in countries, cost assessment is a vital factor to consider. The cost needed to treat one cardiovascular event is also compared between both groups. The occurrence of safety events will also be evaluated at each follow-up point. CONCLUSION: This pragmatic study aims to compare the efficacy, safety and cost-effectiveness of dapagliflozin versus sacubitril/valsartan in patients with HFrEF in real-world settings. The study aims to provide clinicians with data to make informed decisions regarding the preferred drug class. Additionally, examining the impact of ARNI and SGLT2i on GDF-15 levels could offer better insights into prognosis among patients with HFrEF. ETHICS AND DISSEMINATION: This study involves human participants and was approved by Institutional Ethics Committee at AlIMS Jodhpur with reference number AIIMS/IEC/2023/5842 approved this study. Participants gave informed consent to participate in the study before taking part. The research findings will be disseminated via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts, and social media. TRIAL REGISTRATION NUMBER: CTRI/2023/12/060772.