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

August 16, 2023 updated by: Ludhmila Abrahão Hajjar MD, PhD, University of Sao Paulo

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

264

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403-000
        • Instituto do Coracao

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiotoxicity
Time Frame: 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).
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular dysfunction
Time Frame: 3, 6 and 12 months
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
Time Frame: 3, 6 and 12 months
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
Time Frame: 6 and 12 months
Elevation of biomarkers (troponin T > 99th percentile and/or NT-proBNP > 125 pg/mL).
6 and 12 months
Oxygen consumption
Time Frame: 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
6 and 12 months
Ventricular diameters
Time Frame: 3, 6 and 12 months
Ventricular diameters measured by transthoracic echocardiogram
3, 6 and 12 months
Myocardial work
Time Frame: 3, 6 and 12 months
Global work index (GWI) and global constructive work (GCW) measured by transthoracic echocardiogram
3, 6 and 12 months
Diastolic dysfunction
Time Frame: 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.
3, 6 and 12 months
Composite endpoint of mortality or major cardiovascular outcomes
Time Frame: 3, 6 and 12 months
Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, symptomatic heart failure or complex arrhythmia).
3, 6 and 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life measured by EQ-5D-3L (EuroQol 5 Dimension 3 Level) questionnaire
Time Frame: 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.
3, 6 and 12 months
Medication adherence
Time Frame: 3, 6 and 12 months
Medication adherence rate measured by the Morisky-Green index
3, 6 and 12 months
Oncological Treatment Discontinuation Rate
Time Frame: 12 months
12 months
Tumor Recurrence
Time Frame: 12 months
12 months
Hospitalization Rate
Time Frame: 12 months
12 months
Mortality Rate
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2023

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

August 7, 2023

First Submitted That Met QC Criteria

August 16, 2023

First Posted (Actual)

August 22, 2023

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPIROTOX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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