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

Sponsor
University of Sao Paulo (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06005259
Collaborator
(none)
264
Enrollment
1
Location
2
Arms
26
Anticipated Duration (Months)
10.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
264 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Prevention
Official Title:
Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial (SPIROTOX Trial)
Anticipated Study Start Date :
Oct 1, 2023
Anticipated Primary Completion Date :
Oct 1, 2025
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention

Participants will be administered 25 mg of spironolactone daily for 12 months, beginning 5 to 15 days prior to chemotherapy.

Drug: Spironolactone
Spironolactone 25 mg capsule
Placebo Comparator: Control

Participants will be given placebo daily for 12 months, beginning 5 to 15 days prior to chemotherapy.

Drug: Placebo
Placebo capsule

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. Ventricular function [3, 6 and 12 months]

    Relative reduction in global longitudinal strain ≥ 15%, observed on transthoracic echocardiogram and cardiac magnetic resonance imaging

  3. Incidence of myocardial injury [6 and 12 months]

    Elevation of biomarkers (troponin T > 99th percentile and/or NT-proBNP > 125 pg/mL).

  4. 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

  5. Ventricular diameters [3, 6 and 12 months]

    Ventricular diameters measured by transthoracic echocardiogram

  6. Myocardial work [3, 6 and 12 months]

    Global work index (GWI) and global constructive work (GCW) measured by transthoracic echocardiogram

  7. 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.

  8. 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).

Other Outcome Measures

  1. 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.

  2. Medication adherence [3, 6 and 12 months]

    Medication adherence rate measured by the Morisky-Green index

  3. Oncological Treatment Discontinuation Rate [12 months]

  4. Tumor Recurrence [12 months]

  5. Hospitalization Rate [12 months]

  6. Mortality Rate [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Instituto do Coração São Paulo Brazil 05403-000

Sponsors and Collaborators

  • University of Sao Paulo

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ludhmila Abrahão Hajjar MD, PhD, Full Professor, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT06005259
Other Study ID Numbers:
  • SPIROTOX
First Posted:
Aug 22, 2023
Last Update Posted:
Aug 22, 2023
Last Verified:
Aug 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Ludhmila Abrahão Hajjar MD, PhD, Full Professor, University of Sao Paulo
Cardiotoxicity
Anthracyclines
Spironolactone
Additional relevant MeSH terms:
Cardiotoxicity
Spironolactone

Study Results

No Results Posted as of Aug 22, 2023