Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity

NCT06888505 | Completed Phase 2

• 3 other identifiers: HSaeedHawler Medical UniversityDuhok Directorate of Health
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief 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

Cardiotoxicity; Anthracyclines-Induced 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 assessed by echocardiography.

  Change in left ventricular function from baseline to 4 months was assessed using left ventricular ejection fraction (LVEF) as the principal systolic measure and transmitral E/A ratio as an exploratory filling index. 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.

  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

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

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

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, Duhok Governorate, 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: Participants were randomized using a computer-generated block randomization sequence. Allocation concealment was maintained using sequentially numbered, sealed treatment containers prepared before participant enrollment. Dapagliflozin and placebo tablets were matched in appearance, packaging, and labeling. Participants, care providers, investigators, and outcome assessors were blinded to treatment allocation.
• 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: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)