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Randomized Controlled Trial
. 2020 Feb 4;21(1):137.
doi: 10.1186/s13063-019-3963-6.

Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial)

Rodrigo Carrasco  1   2 , María Cristina Ramirez  3 , Kjersti Nes  3 , Andrés Schuster  1 , Rubén Aguayo  3 , Marcelo Morales  1   3 , Cristobal Ramos  4 , Daniel Hasson  4 , Camilo G Sotomayor  5 , Pablo Henriquez  3 , Ignacio Cortés  3 , Marcia Erazo  6 , Claudio Salas  7 , Juan G Gormaz  8
Affiliations
Randomized Controlled Trial

Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial)

Rodrigo Carrasco et al. Trials. .

Abstract

Background: Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a β-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the β-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo.

Methods/design: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing.

Discussion: We expect a group of anthracycline-treated breast cancer patients exposed to carvedilol and non-hypoxic myocardial preconditioning with DHA to show less subclinical cardiotoxicity manifestations than a comparable group exposed to placebo.

Trial registration: ISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.

Keywords: Anthracyclines; CarDHA; Carvedilol; Chemotherapy-induced cardiotoxicity; DHA; Study protocol.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Timeline of the Carvedilol-DHA (CarDHA) trial. hs-cTnT high-sensitivity cardiac troponin T, NT-ProBNP NT-proB-type natriuretic peptide, EKG resting electrocardiogram, ECHO echocardiography, CMR cardiac magnetic resonance, DHA docosahexaenoic acid
Fig. 2
Fig. 2
Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) Figure (required for study protocols). CMR cardiac magnetic resonance, DHA docosahexaenoic acid, ECHO echocardiography, hs-cTnT high-sensitivity cardiac troponin T, NT-ProBNP NT-proB-type natriuretic peptide, EKG resting electrocardiogram
Fig. 3
Fig. 3
Flow chart of the Carvedilol-DHA (CarDHA) trial
See this image and copyright information in PMC

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