Finerenone and Cardiac Remodeling

Summary

The goal of this clinical trial is to learn if the drug finerenone (Karendia) can improve heart function in participants who are at risk for heart and kidney disease. The main question it aims to answer is whether adding finerenone to standard-of-care heart failure medical therapies will beneficially alter the heart structure and function of people who have risk factors for heart and kidney complications and whose left side of the heart is enlarged. The researchers will compare finerenone to a placebo (a look-alike substance that contains no drug) to see if finerenone improves heart structure and function. Participants will: * take a finerenone or a placebo tablet once a day for 12 months * have a cardiac magnetic resonance imaging (cMRI; a safe, non-invasive scan to measure heart mass, stiffness and function) test at the beginning of the study and 12 months later * visit the clinic after one, three, six and twelve months to assess overall health and/or perform blood or urine tests

Timeline

Start

2025-12

Primary completion

2030-12

Completion

2030-12

Publications

• Background Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D. Effects of the Angiotensin-Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta-Analysis. J Am Heart Assoc. 2019 Jul 2;8(13):e012272. doi: 10.1161/JAHA.119.012272. Epub 2019 Jun 26.
• Background Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, Garcia-Ropero A, Mancini D, Pinney S, Macaluso F, Sartori S, Roque M, Sabatel-Perez F, Rodriguez-Cordero A, Zafar MU, Fergus I, Atallah-Lajam F, Contreras JP, Varley C, Moreno PR, Abascal VM, Lala A, Tamler R, Sanz J, Fuster V, Badimon JJ; EMPA-TROPISM (ATRU-4) Investigators. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction. J Am Coll Cardiol. 2021 Jan 26;77(3):243-255. doi: 10.1016/j.jacc.2020.11.008. Epub 2020 Nov 13.
• Background Kasama S, Toyama T, Sumino H, Matsumoto N, Sato Y, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Additive effects of spironolactone and candesartan on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure. J Nucl Med. 2007 Dec;48(12):1993-2000. doi: 10.2967/jnumed.107.045427. Epub 2007 Nov 15.
• Background Dorr K, Kammerlander A, Lauriero F, Lorenz M, Marculescu R, Beitzke D. Effect of etelcalcetide versus alfacalcidol on left ventricular function and feature-tracking cardiac magnetic resonance imaging in hemodialysis-a post-hoc analysis of a randomized, controlled trial. J Cardiovasc Magn Reson. 2023 Nov 6;25(1):62. doi: 10.1186/s12968-023-00975-4.
• Background Everett RJ, Tastet L, Clavel MA, Chin CWL, Capoulade R, Vassiliou VS, Kwiecinski J, Gomez M, van Beek EJR, White AC, Prasad SK, Larose E, Tuck C, Semple S, Newby DE, Pibarot P, Dweck MR. Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis: A Multicenter Cardiac Magnetic Resonance Study. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007451. doi: 10.1161/CIRCIMAGING.117.007451.
• Background Biederman RW, Magovern JA, Grant SB, Williams RB, Yamrozik JA, Vido DA, Rathi VK, Rayarao G, Caruppannan K, Doyle M. LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association. J Cardiothorac Surg. 2011 Apr 14;6:53. doi: 10.1186/1749-8090-6-53.
• Background Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Brighetti G, Marino P, Zardini P. Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol. 2002 Jul 17;40(2):304-10. doi: 10.1016/s0735-1097(02)01965-4.
• Background Kosmala W, Przewlocka-Kosmala M, Szczepanik-Osadnik H, Mysiak A, Marwick TH. Fibrosis and cardiac function in obesity: a randomised controlled trial of aldosterone blockade. Heart. 2013 Mar;99(5):320-6. doi: 10.1136/heartjnl-2012-303329. Epub 2013 Jan 23.
• Background Chan AK, Sanderson JE, Wang T, Lam W, Yip G, Wang M, Lam YY, Zhang Y, Yeung L, Wu EB, Chan WW, Wong JT, So N, Yu CM. Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure. J Am Coll Cardiol. 2007 Aug 14;50(7):591-6. doi: 10.1016/j.jacc.2007.03.062. Epub 2007 Jul 30.
• Background Vizzardi E, D'Aloia A, Giubbini R, Bordonali T, Bugatti S, Pezzali N, Romeo A, Dei Cas A, Metra M, Dei Cas L. Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure. Am J Cardiol. 2010 Nov 1;106(9):1292-6. doi: 10.1016/j.amjcard.2010.06.052. Epub 2010 Sep 9.
• Background Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, Zuo F, Quan A, Farkouh ME, Fitchett DH, Goodman SG, Goldenberg RM, Al-Omran M, Gilbert RE, Bhatt DL, Leiter LA, Juni P, Zinman B, Connelly KA. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation. 2019 Nov 19;140(21):1693-1702. doi: 10.1161/CIRCULATIONAHA.119.042375. Epub 2019 Aug 22.
• Background Zhou D, Huang Y, Cai A, Yan M, Cheng Q, Feng X, Nie Z, Feng Y. Longitudinal Study of Left Ventricular Mass Index Trajectories and Risk of Mortality in Hypertension: A Cohort Study. J Am Heart Assoc. 2023 May 2;12(9):e028568. doi: 10.1161/JAHA.122.028568. Epub 2023 Apr 29.
• Background Verma A, Meris A, Skali H, Ghali JK, Arnold JM, Bourgoun M, Velazquez EJ, McMurray JJ, Kober L, Pfeffer MA, Califf RM, Solomon SD. Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study. JACC Cardiovasc Imaging. 2008 Sep;1(5):582-91. doi: 10.1016/j.jcmg.2008.05.012.
• Background Rosch S, Kresoja KP, Besler C, Fengler K, Schober AR, von Roeder M, Lucke C, Gutberlet M, Klingel K, Thiele H, Rommel KP, Lurz P. Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction. Circulation. 2022 Aug 16;146(7):506-518. doi: 10.1161/CIRCULATIONAHA.122.059280. Epub 2022 Jul 8.
• Background Playford D, Strange G, Joseph M, Perry R, Chan YK, Strom JB, Spetko N, Harris SA, Stewart S, Selvanayagam JB. Increasing Left Ventricular Mass and Death in Men and Women Investigated With Echocardiography. J Am Heart Assoc. 2025 Dec 16;14(24):e041927. doi: 10.1161/JAHA.125.041927. Epub 2025 Dec 11.
• Background Maki KC, Wilcox ML, Dicklin MR, Kakkar R, Davidson MH. Left ventricular mass regression, all-cause and cardiovascular mortality in chronic kidney disease: a meta-analysis. BMC Nephrol. 2022 Jan 16;23(1):34. doi: 10.1186/s12882-022-02666-1.
• Background Laukkanen JA, Khan H, Kurl S, Willeit P, Karppi J, Ronkainen K, Di Angelantonio E. Left ventricular mass and the risk of sudden cardiac death: a population-based study. J Am Heart Assoc. 2014 Nov 5;3(6):e001285. doi: 10.1161/JAHA.114.001285.
• Background Kawel-Boehm N, Kronmal R, Eng J, Folsom A, Burke G, Carr JJ, Shea S, Lima JAC, Bluemke DA. Left Ventricular Mass at MRI and Long-term Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA). Radiology. 2019 Oct;293(1):107-114. doi: 10.1148/radiol.2019182871. Epub 2019 Aug 27.
• Background Gehlken C, Screever EM, Suthahar N, van der Meer P, Westenbrink BD, Coster JE, Van Veldhuisen DJ, de Boer RA, Meijers WC. Left atrial volume and left ventricular mass indices in heart failure with preserved and reduced ejection fraction. ESC Heart Fail. 2021 Aug;8(4):2458-2466. doi: 10.1002/ehf2.13366. Epub 2021 Jun 4.
• Background Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, Rokkedal J, Harris K, Aurup P, Dahlof B. Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA. 2004 Nov 17;292(19):2350-6. doi: 10.1001/jama.292.19.2350.
• Background de Simone G, Gottdiener JS, Chinali M, Maurer MS. Left ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study. Eur Heart J. 2008 Mar;29(6):741-7. doi: 10.1093/eurheartj/ehm605. Epub 2008 Jan 19.
• Background Brown LAE, Wahab A, Ikongo E, Saunderson CED, Jex N, Thirunavukarasu S, Chowdhary A, Das A, Craven TP, Levelt E, Dall'Armellina E, Knott KD, Greenwood JP, Moon JC, Xue H, Kellman P, Plein S, Swoboda PP. Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction. Eur Heart J Cardiovasc Imaging. 2022 Dec 19;24(1):38-45. doi: 10.1093/ehjci/jeac204.
• Background Anstey DE, Tanner RM, Booth JN 3rd, Bress AP, Diaz KM, Sims M, Ogedegbe G, Muntner P, Abdalla M. Inappropriate Left Ventricular Mass and Cardiovascular Disease Events and Mortality in Blacks: The Jackson Heart Study. J Am Heart Assoc. 2019 Aug 20;8(16):e011897. doi: 10.1161/JAHA.118.011897. Epub 2019 Aug 13.
• Background Gaasch WH, Zile MR. Left ventricular structural remodeling in health and disease: with special emphasis on volume, mass, and geometry. J Am Coll Cardiol. 2011 Oct 18;58(17):1733-40. doi: 10.1016/j.jacc.2011.07.022.
• Background Zhang Y, Zhang X, Wang Y, Hu X, Wang B, Yang J, Zhao X, Zhang L. Relationship between diffuse fibrosis assessed by CMR and depressed myocardial strain in different stages of heart failure. Eur J Radiol. 2023 Jul;164:110848. doi: 10.1016/j.ejrad.2023.110848. Epub 2023 Apr 26.
• Background Schelbert EB, Fridman Y, Wong TC, Abu Daya H, Piehler KM, Kadakkal A, Miller CA, Ugander M, Maanja M, Kellman P, Shah DJ, Abebe KZ, Simon MA, Quarta G, Senni M, Butler J, Diez J, Redfield MM, Gheorghiade M. Temporal Relation Between Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction: Association With Baseline Disease Severity and Subsequent Outcome. JAMA Cardiol. 2017 Sep 1;2(9):995-1006. doi: 10.1001/jamacardio.2017.2511.
• Background Garg P, Assadi H, Jones R, Chan WB, Metherall P, Thomas R, van der Geest R, Swift AJ, Al-Mohammad A. Left ventricular fibrosis and hypertrophy are associated with mortality in heart failure with preserved ejection fraction. Sci Rep. 2021 Jan 12;11(1):617. doi: 10.1038/s41598-020-79729-6.
• Background von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Role of cardiovascular magnetic resonance in the guidelines of the European Society of Cardiology. J Cardiovasc Magn Reson. 2016 Jan 22;18:6. doi: 10.1186/s12968-016-0225-6.
• Background Karamitsos TD, Arvanitaki A, Karvounis H, Neubauer S, Ferreira VM. Myocardial Tissue Characterization and Fibrosis by Imaging. JACC Cardiovasc Imaging. 2020 May;13(5):1221-1234. doi: 10.1016/j.jcmg.2019.06.030. Epub 2019 Sep 18.
• Background Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S. Cardiac T1 Mapping and Extracellular Volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson. 2016 Nov 30;18(1):89. doi: 10.1186/s12968-016-0308-4.
• Background Gupta S, Ge Y, Singh A, Grani C, Kwong RY. Multimodality Imaging Assessment of Myocardial Fibrosis. JACC Cardiovasc Imaging. 2021 Dec;14(12):2457-2469. doi: 10.1016/j.jcmg.2021.01.027. Epub 2021 May 19.
• Background Ambale-Venkatesh B, Lima JA. Cardiac MRI: a central prognostic tool in myocardial fibrosis. Nat Rev Cardiol. 2015 Jan;12(1):18-29. doi: 10.1038/nrcardio.2014.159. Epub 2014 Oct 28.
• Background Ali ND, Behairy N, Kharabish A, Elmozy W, Hegab AY, Saraya S. Cardiac MRI T1 mapping and extracellular volume application in hypertrophic cardiomyopathy. Egypt J Radiol Nucl Med. 2021;52:58.
• Background Unlu S, Ozden O, Celik A. Imaging in Heart Failure with Preserved Ejection Fraction: A Multimodality Imaging Point of View. Card Fail Rev. 2023 Apr 4;9:e04. doi: 10.15420/cfr.2022.27. eCollection 2023.
• Background Rajiah PS, Francois CJ, Leiner T. Cardiac MRI: State of the Art. Radiology. 2023 May;307(3):e223008. doi: 10.1148/radiol.223008. Epub 2023 Apr 11.
• Background Liu C, Ferrari VA, Han Y. Cardiovascular Magnetic Resonance Imaging and Heart Failure. Curr Cardiol Rep. 2021 Mar 8;23(4):35. doi: 10.1007/s11886-021-01464-9.
• Background Han Y, Chen Y, Ferrari VA. Contemporary Application of Cardiovascular Magnetic Resonance Imaging. Annu Rev Med. 2020 Jan 27;71:221-234. doi: 10.1146/annurev-med-041818-015923.
• Background Assadi H, Jones R, Swift AJ, Al-Mohammad A, Garg P. Cardiac MRI for the prognostication of heart failure with preserved ejection fraction: A systematic review and meta-analysis. Magn Reson Imaging. 2021 Feb;76:116-122. doi: 10.1016/j.mri.2020.11.011. Epub 2020 Nov 19.
• Background Smiseth OA, Morris DA, Cardim N, Cikes M, Delgado V, Donal E, Flachskampf FA, Galderisi M, Gerber BL, Gimelli A, Klein AL, Knuuti J, Lancellotti P, Mascherbauer J, Milicic D, Seferovic P, Solomon S, Edvardsen T, Popescu BA; Reviewers: This document was reviewed by members of the 2018-2020 EACVI Scientific Documents Committee. Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2022 Jan 24;23(2):e34-e61. doi: 10.1093/ehjci/jeab154.
• Background Delcayre C, Silvestre JS, Garnier A, Oubenaissa A, Cailmail S, Tatara E, Swynghedauw B, Robert V. Cardiac aldosterone production and ventricular remodeling. Kidney Int. 2000 Apr;57(4):1346-51. doi: 10.1046/j.1523-1755.2000.00973.x.
• Background Okoshi MP, Yan X, Okoshi K, Nakayama M, Schuldt AJ, O'Connell TD, Simpson PC, Lorell BH. Aldosterone directly stimulates cardiac myocyte hypertrophy. J Card Fail. 2004 Dec;10(6):511-8. doi: 10.1016/j.cardfail.2004.03.002.
• Background Brilla CG, Weber KT. Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med. 1992 Dec;120(6):893-901.
• Background Tanabe A, Naruse M, Naruse K, Hase M, Yoshimoto T, Tanaka M, Seki T, Demura R, Demura H. Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension. Hypertens Res. 1997 Jun;20(2):85-90. doi: 10.1291/hypres.20.85.
• Background Rossi GP, Di Bello V, Ganzaroli C, Sacchetto A, Cesari M, Bertini A, Giorgi D, Scognamiglio R, Mariani M, Pessina AC. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension. 2002 Jul;40(1):23-7. doi: 10.1161/01.hyp.0000023182.68420.eb.
• Background Buffolo F, Tetti M, Mulatero P, Monticone S. Aldosterone as a Mediator of Cardiovascular Damage. Hypertension. 2022 Sep;79(9):1899-1911. doi: 10.1161/HYPERTENSIONAHA.122.17964. Epub 2022 Jun 29.

Drugs

Indications