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

Phase 4

Not yet recruiting

• Conditions: Cardiotoxicity; Chemotherapy Effect; Neoplasms; Heart Failure
• Interventions: Drug: Spironolactone; Drug: Placebo

• Registration Number: NCT06005259
• Lead Sponsor: University of Sao Paulo

Brief 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.

Detailed Description

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.

Study Timeline

• Status Verified: 2023-08
• Study First Submitted: 2023-08-07
• Study First Submitted QC: 2023-08-16
• Last Update Submitted: 2023-08-16
• Study First Posted: 2023-08-22
• Last Update Posted: 2023-08-22
• Study Start: 2023-10-01
• Primary Completion: 2025-10-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 264

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Spironolactone	Participants will be administered 25 mg of spironolactone daily for 12 months, beginning 5 to 15 days prior to chemotherapy.
Control	Placebo	Participants will be given placebo daily for 12 months, beginning 5 to 15 days prior to chemotherapy.

Primary Outcome Measures

Name	Time	Method
Cardiotoxicity	12 months	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).

Secondary Outcome Measures

Name	Time	Method
Incidence of myocardial injury	6 and 12 months	Elevation of biomarkers (troponin T \> 99th percentile and/or NT-proBNP \> 125 pg/mL).
Composite endpoint of mortality or major cardiovascular outcomes	3, 6 and 12 months	Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, symptomatic heart failure or complex arrhythmia).
Left ventricular dysfunction	3, 6 and 12 months	Decrease in ejection fraction (LVEF) ≥ 10% to LVEF \< 50% seen on transthoracic echocardiogram and cardiac magnetic resonance imaging
Ventricular function	3, 6 and 12 months	Relative reduction in global longitudinal strain ≥ 15%, observed on transthoracic echocardiogram and cardiac magnetic resonance imaging
Oxygen consumption	6 and 12 months	Measurement of oxygen consumption (VO2), ventilatory equivalents for oxygen (VE/VO2) and for carbon dioxide (VE/VCO2) by cardiopulmonary exercise test
Ventricular diameters	3, 6 and 12 months	Ventricular diameters measured by transthoracic echocardiogram
Myocardial work	3, 6 and 12 months	Global work index (GWI) and global constructive work (GCW) measured by transthoracic echocardiogram
Diastolic dysfunction	3, 6 and 12 months	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.

Trial Locations

Locations (1)

Instituto do Coração; 🇧🇷 São Paulo, Brazil