Cardiotoxicity, Chemotherapy Effect, Heart Failure, Neoplasms
Conditions
Keywords
Cardiotoxicity, Anthracyclines, Spironolactone
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.
Interventions
DRUGSpironolactone
Spironolactone 25 mg capsule
DRUGPlacebo
Placebo capsule
Sponsors
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Ventricular function | 3, 6 and 12 months | Relative reduction in global longitudinal strain ≥ 15%, observed on transthoracic echocardiogram and cardiac magnetic resonance imaging |
| Incidence of myocardial injury | 6 and 12 months | Elevation of biomarkers (troponin T \> 99th percentile and/or NT-proBNP \> 125 pg/mL). |
| 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. |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Oncological Treatment Discontinuation Rate | 12 months | — |
| Tumor Recurrence | 12 months | — |
| Hospitalization Rate | 12 months | — |
| Mortality Rate | 12 months | — |
| Medication adherence | 3, 6 and 12 months | Medication adherence rate measured by the Morisky-Green index |
| Quality of life measured by EQ-5D-3L (EuroQol 5 Dimension 3 Level) questionnaire | 3, 6 and 12 months | The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 3 levels; 1 indicates better health state (no problems); 3 indicate worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. |
Countries
Brazil
Contacts
Primary ContactLucas T Kawahara
Backup ContactLudhmila A Hajjar, MD, PhD
Outcome results
None listed