Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity

NCT06888505 | Completed Phase 2

• 3 other identifiers: HSaeedHawler Medical UniversityDuhok Directorate of Health
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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. 1.dapagliflozin 10 mg orally once daily for 4 months plus standard chemotherapy; or
2. 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.

Conditions

Anthracyclines-Induced Cardiotoxicity; Cardiotoxicity

Keywords

cardiotoxicity; Anthracycline-induced cardiotoxicity; Dapagliflozin; SGLT2 inhibitors; cardio-oncology; Cardiac biomarkers in chemotherapy; Heart failure in cancer patients

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Function (Systolic and Diastolic)

  Echocardiographic assessment of left ventricular systolic function (LVEF) and diastolic function (E/A ratio, diastolic dysfunction grade) to detect anthracycline-induced cardiotoxicity.Measurement Tool: Echocardiography (using a 2D echocardiogram).

  Evaluated at baseline and 4 months after initiation of chemotherapy.

Secondary Outcomes (7)

• Cardiac Troponin I Levels

  Evaluated at baseline and 4 months after initiation of chemotherapy.

• NT-proBNP Levels

  Evaluated at baseline and 4 months after initiation of chemotherapy.

• Galectin-3 Levels

  Evaluated at baseline and 4 months after initiation of chemotherapy.

• CA 15-3 Levels

  Evaluated at baseline and 4 months after initiation of chemotherapy.

• Kidney Function Tests

  Evaluated at baseline and 4 months after initiation of chemotherapy.

Study Arms (2)

Dapagliflozin Arm

ACTIVE COMPARATOR

Participants in this arm received dapagliflozin 10 mg orally once daily in addition to their standard anthracycline-based chemotherapy regimen. Dapagliflozin was continued daily for four months (throughout the chemotherapy treatment period). The study evaluated its potential cardioprotective effects against anthracycline-induced cardiac toxicity using echocardiography, cardiac biomarkers, and safety monitoring.

Drug: Dapagliflozin (Forxiga)

Control Arm

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Dapagliflozin (Forxiga) DRUG

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.

Also known as: Farxiga

Dapagliflozin Arm

Placebo OTHER

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.

Also known as: Inactive tablet

Control Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed breast cancer (or other cancers as relevant to the study).
• Age 18-70 years.
• Planned treatment with anthracycline-based chemotherapy
• Normal kidney function, defined as serum creatinine 0.6-1.2 mg/dL.
• Normal liver function, defined as ALT and AST 10-40 U/L.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Willingness to participate and provide written informed consent.

You may not qualify if:

• History of symptomatic heart failure (NYHA class III-IV) or prior anthracycline-related cardiac dysfunction.
• Previous use of Dapagliflozin.
• Pregnancy or breastfeeding.
• Severe renal impairment (eGFR \< 30 mL/min/1.73m²).
• Uncontrolled diabetes mellitus (HbA1c \> 9%).
• Active or recurrent urinary tract infections (UTIs) within the last 6 months.
• Known hypersensitivity to Dapagliflozin or related compounds.
• Concurrent participation in another clinical trial investigating cardioprotective agents.

Sponsors & Collaborators

• Hawler Medical University: lead
• University of Zakho: collaborator

Study Sites (1)

Azadi Oncology Centre

Duhok, 42001, Iraq

Location

MeSH Terms

Conditions

Cardiotoxicity

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• Hakar A Saeed, M.Sc

  University of Zakho

  PRINCIPAL INVESTIGATOR

• Nidhal A Mohammed Ali, PhD

  Hawler Medical University

  PRINCIPAL INVESTIGATOR

• Ramadhan T Othman, PhD

  University of Duhok

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind, placebo-controlled trial in which participants, care providers, investigators, and outcomes assessors are blinded to treatment allocation. Randomization and treatment allocation will be conducted through a centralized system, and placebo tablets will be matched to ensure blinding.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator; PhD Candidate, Hawler Medical University; Lecturer, University of Zakho

Model Details: This study is a randomized, double-blind, placebo-controlled trial investigating the efficacy of Dapagliflozin in preventing chemotherapy-induced cardiotoxicity in cancer patients receiving anthracycline-based chemotherapy.

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 21, 2025
• Study Start: September 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 6, 2025
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)