Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity

Summary

Brief Summary Anthracyclines (e.g., doxorubicin) are effective anticancer agents but can cause dose-dependent, often irreversible cardiotoxicity via oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. Trastuzumab is also associated with left-ventricular dysfunction, typically reversible. The original protocol planned cohorts for both drug classes; however, no trastuzumab patients were enrolled due to feasibility, and the final study focused exclusively on anthracycline-treated patients.

Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor approved for diabetes and heart failure, has cardioprotective properties beyond glycemic control (reduced oxidative stress, inflammation, and fibrosis). We evaluated whether dapagliflozin mitigates anthracycline-induced cardiotoxicity.

This randomized, double-blind, placebo-controlled trial enrolled 90 patients receiving anthracycline-based chemotherapy. Participants were randomized 1:1 to:

1. dapagliflozin 10 mg orally once daily for 4 months plus standard chemotherapy; or
2. matching placebo once daily for 4 months plus standard chemotherapy. Primary outcome: change in left ventricular ejection fraction (LVEF) and diastolic function (e.g., E/A ratio, e'/E/e', diastolic dysfunction grade) from baseline to 16 weeks after chemotherapy initiation, measured by echocardiography.

Secondary outcomes: Troponin I, NT-proBNP, Galectin-3, CA 15-3, renal indices (creatinine, BUN, eGFR), and incidence of symptomatic cardiac dysfunction (e.g., heart failure, arrhythmias, myocardial infarction). Safety events related to chemotherapy or dapagliflozin were recorded and graded by CTCAE.

Assessments were performed at two time points only-baseline (pre-chemotherapy) and 16 weeks after initiation of chemotherapy; adverse events were collected continuously through the 16-week study period.

If effective, dapagliflozin could represent a practical cardioprotective strategy for patients receiving anthracyclines, potentially improving cardiovascular outcomes without compromising cancer therapy.

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