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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)

Authors
  • Carrasco, Rodrigo1, 2
  • Ramirez, María Cristina3
  • Nes, Kjersti3
  • Schuster, Andrés1
  • Aguayo, Rubén3
  • Morales, Marcelo1, 3
  • Ramos, Cristobal1
  • Hasson, Daniel1
  • Sotomayor, Camilo G.4
  • Henriquez, Pablo3
  • Cortés, Ignacio3
  • Erazo, Marcia5
  • Salas, Claudio6
  • Gormaz, Juan G.6
  • 1 Clinica Alemana de Santiago, Santiago, Chile , Santiago (Chile)
  • 2 Hospital del Salvador, Santiago, Chile , Santiago (Chile)
  • 3 Hospital San Juan de Dios, Santiago, Chile , Santiago (Chile)
  • 4 University Medical Center Groningen, Groningen, The Netherlands , Groningen (Netherlands)
  • 5 University of Chile, Santiago, Chile , Santiago (Chile)
  • 6 Clinica Alemana de Santiago, Vitacura 5951, Santiago, Chile , Santiago (Chile)
Type
Published Article
Journal
Trials
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 04, 2020
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s13063-019-3963-6
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundAnthracycline-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/designWe 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.DiscussionWe 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 registrationISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.

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