Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity

Summary

Anthracyclines, such as doxorubicin, are effective anticancer agents but may cause dose-dependent cardiac injury, including early changes in left ventricular function and cardiac biomarkers. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor with established cardiovascular benefits in heart failure and potential cardioprotective effects beyond glucose lowering, including modulation of oxidative stress, inflammation, myocardial energetics and fibrotic remodeling.

This randomized, double-blind, placebo-controlled phase 2 trial evaluated whether dapagliflozin attenuates early anthracycline-associated cardiac functional and biomarker changes in adults receiving anthracycline-based chemotherapy. A total of 94 participants were randomized in a 1:1 ratio to receive dapagliflozin 10 mg orally once daily plus standard anthracycline-based chemotherapy or matching placebo plus standard anthracycline-based chemotherapy for 4 months. Ninety participants completed the 4-month follow-up and were included in complete-case analyses.

The primary echocardiographic outcome was change in left ventricular function from baseline to 4 months. Left ventricular systolic function was assessed using left ventricular ejection fraction (LVEF) as the principal systolic measure. Transmitral E/A ratio was analyzed as an exploratory filling index because it was consistently available across participants. Tissue Doppler indices and comprehensive diastolic dysfunction grading were not consistently available and were therefore not used for formal diastolic grading in the final analysis.

Secondary outcomes included cardiac troponin I, NT-proBNP, galectin-3, CA 15-3, renal and hepatic function parameters, and adverse events. Echocardiography and laboratory biomarkers were assessed at baseline and 4 months, while adverse events were monitored continuously throughout the study period.

Conditions

• Anthracyclines-Induced Cardiotoxicity
• Cardiotoxicity

Interventions

DRUG

Dapagliflozin (Forxiga)

Participants in the dapagliflozin arm received dapagliflozin 10 mg tablets, administered orally once daily for 4 months, in addition to their standard anthracycline-based chemotherapy regimen. This treatment was given continuously throughout the chemotherapy period to evaluate its cardioprotective effects against anthracycline-induced cardiac toxicity.

OTHER

Placebo

Participants in the control arm received a placebo tablet identical in appearance, dosage form, frequency, and duration to dapagliflozin, but containing no active ingredients. The placebo was administered orally once daily for 4 months alongside the participant's standard anthracycline-based chemotherapy regimen and served as the control to evaluate the cardioprotective efficacy of dapagliflozin.

Sponsors & Collaborators

• University of Zakho

  collaborator UNKNOWN

• Hawler Medical University

  lead OTHER

Principal Investigators

• Hakar A Saeed, M.Sc · University of Zakho

• Nidhal A Mohammed Ali, PhD · Hawler Medical University

• Ramadhan T Othman, PhD · University of Duhok

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-09-01

Primary Completion

2025-09-01

Completion

2025-09-06

Countries

• Iraq

Study Locations