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)

Autor: Camilo G. Sotomayor, Cristobal Ramos, Juan G. Gormaz, Kjersti Nes, Daniel Hasson, Ignacio Cortés, Rodrigo Carrasco, María Cristina Ramirez, Andres Schuster, Marcelo Morales, Rubén Aguayo, Marcia Erazo, Claudio Salas, Pablo Henriquez
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Medicine (miscellaneous)
Pilot Projects
030204 cardiovascular system & hematology
THERAPY
Antioxidants
Ventricular Function
Left
law.invention
0302 clinical medicine
Randomized controlled trial
law
Pharmacology (medical)
Anthracyclines
PROTECTION
Carvedilol
Subclinical infection
lcsh:R5-920
Antibiotics
Antineoplastic
Ejection fraction
Middle Aged
CHEMOTHERAPY
DHA
Treatment Outcome
030220 oncology & carcinogenesis
Ischemic Preconditioning
Myocardial
Cardiology
HEART-FAILURE
Female
FATTY-ACIDS
lcsh:Medicine (General)
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Docosahexaenoic Acids
Anthracycline
Adrenergic beta-Antagonists
Breast Neoplasms
Placebo
ANTHRACYCLINE CARDIOTOXICITY
Young Adult
03 medical and health sciences
Double-Blind Method
Internal medicine
Study protocol
medicine
Humans
BREAST-CANCER
Chemotherapy-induced cardiotoxicity
Aged
Cardiotoxicity
DEXRAZOXANE
business.industry
CarDHA
Stroke Volume
DYSFUNCTION
Clinical trial
Doxorubicin
ATRIAL-FIBRILLATION
business
Biomarkers
Follow-Up Studies
Zdroj: Trials, Vol 21, Iss 1, Pp 1-10 (2020)
TRIALS, 21(1):137. BMC
Trials
ISSN: 1745-6215
Popis: 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.
Databáze: OpenAIRE
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