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

Study Overview
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Brief Summary
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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.

Detailed Description
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Objective: To assess the potential of spironolactone in preventing anthracycline-induced cardiotoxicity among cancer patients. Background: There's ongoing debate and a dearth of evidence regarding the role of mineralocorticoid receptor antagonists, such as spironolactone, in averting anthracycline-induced cardiotoxicity. Study Design: A randomized, double-blind, placebo-controlled trial conducted at a single center. Sample Size: 264 patients. Intervention: Eligible participants will be randomized on a 1:1 basis to either receive spironolactone or a placebo over a 12-month period. Primary Outcome: Incidence of cardiotoxicity at the 12-month mark.

Official Title
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Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial (SPIROTOX Trial)

Conditions
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Cardiotoxicity, Neoplasms, Chemotherapy Effect, Heart Failure

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Participants will be administered 25 mg of spironolactone daily for 12 months, beginning 5 to 15 days prior to chemotherapy. | Drug: Spironolactone<br>* Spironolactone 25 mg capsule<br>|
| Placebo Comparator: Control<br>Participants will be given placebo daily for 12 months, beginning 5 to 15 days prior to chemotherapy. | Drug: Placebo<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiotoxicity | Incidence of cardiotoxicity, defined as: A decrease in ejection fraction (LVEF) by 10% or more to LVEF < 50%, as seen on transthoracic echocardiogram; OR Relative drop in global longitudinal strain greater than 15% compared to baseline, observed on transthoracic echocardiogram; OR New increase in cardiac biomarkers (troponin T > 99th percentile and/or NT-proBNP > 125 pg/mL). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular dysfunction | Decrease in ejection fraction (LVEF) ≥ 10% to LVEF < 50% seen on transthoracic echocardiogram and cardiac magnetic resonance imaging | 3, 6 and 12 months | 
| Ventricular function | Relative reduction in global longitudinal strain ≥ 15%, observed on transthoracic echocardiogram and cardiac magnetic resonance imaging | 3, 6 and 12 months | 
| Incidence of myocardial injury | Elevation of biomarkers (troponin T > 99th percentile and/or NT-proBNP > 125 pg/mL). | 6 and 12 months | 
| Oxygen consumption | Measurement of oxygen consumption (VO2), ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) by cardiopulmonary exercise test | 6 and 12 months | 
| Ventricular diameters | Ventricular diameters measured by transthoracic echocardiogram | 3, 6 and 12 months | 
| Myocardial work | Global work index (GWI) and global constructive work (GCW) measured by transthoracic echocardiogram | 3, 6 and 12 months | 
| Diastolic dysfunction | Assessment by echocardiography the incidence of diastolic dysfunction using the following parameters: peak E-wave velocity, peak A-wave velocity, mitral valve (MV) E/A ratio, MV deceleration time, pulsed-wave tissue doppler imaging e' velocity, Mitral E/e', left atrium maximum volume index, pulmonary vein(PV) systole(S) wave, PV diastole (D) wave, continuous wave (CW) doppler: tricuspid regurgitation, systolic jet velocity; Color M- mode. | 3, 6 and 12 months | 
| Composite endpoint of mortality or major cardiovascular outcomes | Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, symptomatic heart failure or complex arrhythmia). | 3, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiotoxicity, Anthracyclines, Spironolactone