Clinical trial NCT06005259: Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity (SPIROTOX)
Official title: Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial (SPIROTOX Trial)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Cardiotoxicity
Neoplasms
Chemotherapy Effect
Heart Failure
Keywords: Cardiotoxicity
Anthracyclines
Spironolactone
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2023-08-22
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiotoxicity
timeFrame: 12 months
Secondary outcomes:
measure: Left ventricular dysfunction
timeFrame: 3, 6 and 12 months
measure: Ventricular function
timeFrame: 3, 6 and 12 months
measure: Incidence of myocardial injury
timeFrame: 6 and 12 months
measure: Oxygen consumption
timeFrame: 6 and 12 months
measure: Ventricular diameters
timeFrame: 3, 6 and 12 months
measure: Myocardial work
timeFrame: 3, 6 and 12 months
measure: Diastolic dysfunction
timeFrame: 3, 6 and 12 months
measure: Composite endpoint of mortality or major cardiovascular outcomes
timeFrame: 3, 6 and 12 months
Other outcomes:
measure: Quality of life measured by EQ-5D-3L (EuroQol 5 Dimension 3 Level) questionnaire
timeFrame: 3, 6 and 12 months
measure: Medication adherence
timeFrame: 3, 6 and 12 months
measure: Oncological Treatment Discontinuation Rate
timeFrame: 12 months
measure: Tumor Recurrence
timeFrame: 12 months
measure: Hospitalization Rate
timeFrame: 12 months
measure: Mortality Rate
timeFrame: 12 months
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Coração
Study officials:
References:
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