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

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patients diagnosed with cancer indicated for anthracycline chemotherapy treatment
* Age 18 and above
* Signed informed consent form

Exclusion Criteria:

* Previous use of anthracycline.
* Hypersensitivity to any mineralocorticoid receptor antagonists
* Symptoms of heart failure (exertional dyspnea, orthopnea, nocturnal paroxysmal dyspnea, and pulmonary or systemic congestion)
* Left ventricular ejection fraction (LVEF) \< 45%
* Previous diagnosis of cardiomyopathy, coronary artery disease, or moderate to severe mitral or aortic disease
* Renal insufficiency defined as an estimated glomerular filtration rate \< 30 ml/min/m2
* Hyperkalemia, defined as serum potassium ≥ 5.0 mmol/L
* Chronic liver disease, defined aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values more than 3 times the upper limit of normal
* Current participation in another study

• BACKGROUNDVenkatesh P, Kasi A. Anthracyclines. 2023 Jan 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK538187/ PMID 30844214
• BACKGROUNDBarbosa 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. PMID 30673046
• BACKGROUNDRawat 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. PMID 34243633
• BACKGROUNDCardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of Anthracyclines. Front Cardiovasc Med. 2020 Mar 18;7:26. doi: 10.3389/fcvm.2020.00026. eCollection 2020. PMID 32258060
• BACKGROUNDHerrmann 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. PMID 34904661
• BACKGROUNDKalay 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. PMID 17161256