Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity (SPIROTOX)

Summary

The goal of this clinical trial is to evaluate the effect of spironolactone in the primary prevention of cardiotoxicity in cancer patients who are undergoing chemotherapy with anthracycline within 12 months. The main question it aims to answer is: • Does spironolactone reduce the incidence of cardiotoxicity in patients undergoing anthracycline chemotherapy? Participants will: * Be cancer patients over 18 years starting treatment with anthracycline; * Be randomized to receive either spironolactone or a placebo for 1 year; * Undergo assessments of their left ventricular ejection fraction (LVEF), global longitudinal strain, and cardiac biomarkers over the 12-month period. Researchers will compare the spironolactone group to the placebo group to see if cardiotoxicity incidence differs between the two.

Timeline

Start

2023-10-01

Primary completion

2025-10-01

Completion

2025-12-01

Publications

• Background Venkatesh P, Kasi A. Anthracyclines(Archived). 2023 Jan 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK538187/
• Background Barbosa RR, Bourguignon TB, Torres LD, Arruda LS, Jacques TM, Serpa RG, Calil OA, Barbosa LFM. Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers. Rev Assoc Med Bras (1992). 2018 Aug;64(8):745-754. doi: 10.1590/1806-9282.64.08.745.
• Background Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother. 2021 Jul;139:111708. doi: 10.1016/j.biopha.2021.111708. Epub 2021 May 13.
• Background Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of Anthracyclines. Front Cardiovasc Med. 2020 Mar 18;7:26. doi: 10.3389/fcvm.2020.00026. eCollection 2020.
• Background Herrmann J, Lenihan D, Armenian S, Barac A, Blaes A, Cardinale D, Carver J, Dent S, Ky B, Lyon AR, Lopez-Fernandez T, Fradley MG, Ganatra S, Curigliano G, Mitchell JD, Minotti G, Lang NN, Liu JE, Neilan TG, Nohria A, O'Quinn R, Pusic I, Porter C, Reynolds KL, Ruddy KJ, Thavendiranathan P, Valent P. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J. 2022 Jan 31;43(4):280-299. doi: 10.1093/eurheartj/ehab674.
• Background Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, Inanc T, Oguzhan A, Eryol NK, Topsakal R, Ergin A. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006 Dec 5;48(11):2258-62. doi: 10.1016/j.jacc.2006.07.052. Epub 2006 Nov 9.
• Background Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, Kalay N, Dikilitas M, Yarlioglues M, Karaca H, Berk V, Ardic I, Ergin A, Lam YY. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013 Sep 1;167(5):2306-10. doi: 10.1016/j.ijcard.2012.06.023. Epub 2012 Jun 22.
• Background Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR Jr, das Dores Cruz F, Goncalves Brandao SM, Rigaud VOC, Higuchi-Dos-Santos MH, Hajjar LA, Kalil Filho R, Hoff PM, Sahade M, Ferrari MSM, de Paula Costa RL, Mano MS, Bittencourt Viana Cruz CB, Abduch MC, Lofrano Alves MS, Guimaraes GV, Issa VS, Bittencourt MS, Bocchi EA. Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial. J Am Coll Cardiol. 2018 May 22;71(20):2281-2290. doi: 10.1016/j.jacc.2018.02.049. Epub 2018 Mar 11.
• Background Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, Martinelli G, Veglia F, Fiorentini C, Cipolla CM. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006 Dec 5;114(23):2474-81. doi: 10.1161/CIRCULATIONAHA.106.635144. Epub 2006 Nov 13.
• Background Livi L, Barletta G, Martella F, Saieva C, Desideri I, Bacci C, Del Bene MR, Airoldi M, Amoroso D, Coltelli L, Scotti V, Becherini C, Visani L, Salvestrini V, Mariotti M, Pedani F, Bernini M, Sanchez L, Orzalesi L, Nori J, Bianchi S, Olivotto I, Meattini I. Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1544-1549. doi: 10.1001/jamaoncol.2021.3395.
• Background Omland T, Heck SL, Gulati G. The Role of Cardioprotection in Cancer Therapy Cardiotoxicity: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2022 Mar 15;4(1):19-37. doi: 10.1016/j.jaccao.2022.01.101. eCollection 2022 Mar.
• Background Wang Y, Lu X, Wang X, Qiu Q, Zhu P, Ma L, Ma X, Herrmann J, Lin X, Wang W, Xu X. atg7-Based Autophagy Activation Reverses Doxorubicin-Induced Cardiotoxicity. Circ Res. 2021 Oct;129(8):e166-e182. doi: 10.1161/CIRCRESAHA.121.319104. Epub 2021 Aug 13.
• Background Akpek M, Ozdogru I, Sahin O, Inanc M, Dogan A, Yazici C, Berk V, Karaca H, Kalay N, Oguzhan A, Ergin A. Protective effects of spironolactone against anthracycline-induced cardiomyopathy. Eur J Heart Fail. 2015 Jan;17(1):81-9. doi: 10.1002/ejhf.196. Epub 2014 Nov 20.
• Background Davis MK, Villa D, Tsang TSM, Starovoytov A, Gelmon K, Virani SA. Effect of Eplerenone on Diastolic Function in Women Receiving Anthracycline-Based Chemotherapy for Breast Cancer. JACC CardioOncol. 2019 Dec 17;1(2):295-298. doi: 10.1016/j.jaccao.2019.10.001. eCollection 2019 Dec. No abstract available.
• Background Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, Civelli M, Lamantia G, Colombo N, Curigliano G, Fiorentini C, Cipolla CM. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015 Jun 2;131(22):1981-8. doi: 10.1161/CIRCULATIONAHA.114.013777. Epub 2015 May 6.
• Background Lyon AR, Lopez-Fernandez T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, Boriani G, Cardinale D, Cordoba R, Cosyns B, Cutter DJ, de Azambuja E, de Boer RA, Dent SF, Farmakis D, Gevaert SA, Gorog DA, Herrmann J, Lenihan D, Moslehi J, Moura B, Salinger SS, Stephens R, Suter TM, Szmit S, Tamargo J, Thavendiranathan P, Tocchetti CG, van der Meer P, van der Pal HJH; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022 Nov 1;43(41):4229-4361. doi: 10.1093/eurheartj/ehac244. No abstract available.
• Background Laufer-Perl M, Perelman-Gvili M, Sirota Dorfman S, Baruch G, Rothschild E, Beer G, Arbel Y, Arnold JH, Rozenbaum Z, Banai S, Topilsky Y, Kapusta L. Prevalence of Right Ventricle Strain Changes following Anthracycline Therapy. Life (Basel). 2022 Feb 15;12(2):291. doi: 10.3390/life12020291.

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