Cardiac impact of dapagliflozin in advanced chronic kidney disease: rationale and design of the Renal Lifecycle Trial cardiac imaging sub-studies
Year: 2025
Type: article
Study design: Study Protocol
Abstract: ABSTRACT Background Patients with chronic kidney disease (CKD) are frequently hospitalized for heart failure. Sodium-glucose co-transporter 2 (SGLT2)-inhibitors improve cardiorenal outcomes in CKD and heart failure, at least in estimated glomerular filtration rate (eGFR) ranges 20–60 ml/min/1.73 m2, possibly through direct cardiac effects. In the cardiac imaging sub-studies of the Renal Lifecycle Trial, we aim to establish the effects of SGLT2-inhibition on cardiac structure and function in patients with advanced CKD, kidney failure and in kidney transplant recipients. Methods In the Renal Lifecycle Trial, patients with advanced CKD (eGFR ≤25 ml/min/1.73 m2), those treated with hemodialysis or peritoneal dialysis (PD) or kidney transplant recipients (eGFR ≤45 ml/min/1.73 m2), are randomized to receive either dapagliflozin or placebo. The echocardiography sub-study (acronym: STOP-HF-in-PD) will enroll 100 PD-treated patients, who undergo echocardiography at baseline, and at 6 and 12 months post-randomization. In the cardiac magnetic resonance imaging (MRI) sub-study, 250 Renal Lifecycle Trial participants across all three groups (i.e. advanced CKD, dialysis, kidney transplant recipients), including a subset of STOP-HF-in-PD participants, will undergo cardiac MRI at baseline, and at 12 months post-randomization. The primary endpoint of STOP-HF-in-PD is the difference in left ventricular global longitudinal strain, a measure of cardiac function, after 6-months of dapagliflozin compared to placebo. For the cardiac MRI sub-study, the primary endpoint is the difference of indexed left ventricular mass after 12 months of dapagliflozin compared to placebo. Conclusions The Renal Lifecycle Trial cardiac imaging sub-studies will generate novel data on the effects of SGLT2-inhibition on cardiac structure and function in a population with advanced CKD, in whom SGLT2-inhibitor induced cardiovascular protection remains to be established. Clinical Trial Registration The Renal Lifecycle Trial and its sub-studies are registered at ClinicalTrials.gov under registration number NCT05374291.
Source: Clinical Kidney Journal
DOI: 10.1093/ckj/sfaf376
Authors: Micky Karsten, Sunil V Badve, Ron T Gansevoort, Stefan P Berger, Hiddo J L Heerspink, Alferso C Abrahams, Laurent Billot, Rianne H A C M Bon, Mariëlle A C J Gelens, Dean Guinness, Christian Hamilton-Craig, Loek van Heerebeek, Marc H Hemmelder, Lauren Houston, Rebecca Kozor, Dirk R J Kuypers, Helen Monaghan, Bruce Neal, Brendon L Neuen, James Otton, Vlado Perkovic, Adil Rajwani, Angela Y Wang, Marc G Vervloet, Clare Arnott, Lily Jakulj, the Renal Lifecycle Trial Cardiac Imaging Sub-studies Investigators, Ronald van Etten, Karlien Francois, Pedro Gois, Joost van der Heijden, Jane Holt, Shilpa Jesudason, Karen Keung, Yu Sok Kim, Rathika Krishnasamy, Hemant Kulkarni, Joep van der Leeuw, Angela Makris, Rosemary Masterson, Amanda Mather, Gurbey Ocak, Dharmenaan Palamuthusingam, Eugenia Pedagogos, Carl Siegert, Brendan Smyth, Vikas Srivastava, Girish Talaulikar, Rowena Vleut, Femke Waanders, Germaine Wong, Muh Geot Wong, Kate Wyburn
Institutions: Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, UNSW Sydney, The George Institute for Global Health, St George Hospital, University Medical Center Groningen, University of Groningen, University Medical Center Utrecht, Maastricht University Medical Centre, Maastricht University, The University of Queensland, OLVG, Erasmus MC, Erasmus University Rotterdam, The University of Sydney, Royal North Shore Hospital, Universitair Ziekenhuis Leuven, Royal Perth Hospital, Singapore General Hospital, Radboud University Medical Center, Dianet
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,335
Funders: Amgen, Eli Lilly and Company, AstraZeneca, Bayer, GlaxoSmithKline, Sanofi, Biogen, Alexion Pharmaceuticals, CSL Behring, Fresenius Medical Care North America, Duke-NUS Medical School, Incyte, Argenx, National University of Singapore, Nierstichting, Novo Nordisk, Astellas Pharma, Universitair Medisch Centrum Groningen, Idorsia Pharmaceuticals, George Institute for Global Health, Illawarra Shoalhaven Local Health District, Seqirus, Medical Research Council, National Health and Medical Research Council, National Medical Research Council
OpenAlex ID: W4416913706