Dapagliflozin to prevent chemotherapy-related heart damage in breast cancer

Use of Dapagliflozin in Primary Prevention of Cardiotoxicity of Anthracycline Chemotherapy in Breast Cancer Patients

We will test if taking dapagliflozin 10 mg daily prevents heart and blood-vessel damage in adult women receiving anthracycline chemotherapy for breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Medical Centre Ljubljana (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, doxorubicin
• Locations: 1 site (Ljubljana)
• Trial ID: NCT07245069 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial enrolling adult women with breast cancer who will receive (neo)adjuvant anthracycline-based chemotherapy. Participants are randomized to dapagliflozin 10 mg daily or matching placebo started prior to or at the initiation of chemotherapy and followed through treatment and short-term follow-up. Cardiac function (LVEF, GLS, myocardial work), vascular measures (flow-mediated dilation and carotid stiffness), exercise capacity, and multiple cardiac injury and inflammation biomarkers will be measured at baseline and predefined intervals. The trial aims to determine whether dapagliflozin reduces early cardiac and vascular changes associated with anthracycline exposure.

Who should consider this trial

Good fit: Ideal candidates are adult women with histologically confirmed breast cancer who are scheduled to start (neo)adjuvant anthracycline-based chemotherapy and who have no prior heart failure or contraindications to SGLT-2 inhibitors.

Not a fit: Patients with preexisting heart failure, prior left-chest radiotherapy or prior chemotherapy, type 1 diabetes, severe renal or hepatic impairment, or a history of recurrent urinary infections or diabetic ketoacidosis are unlikely to be eligible or to benefit from this intervention.

Why it matters

Potential benefit: If successful, this could reduce the risk of chemotherapy-related heart damage and lower later heart-failure risk in breast cancer survivors.

How similar studies have performed: SGLT-2 inhibitors have shown clear cardiovascular benefit in heart-failure trials and observational data suggest fewer cardiac events after anthracycline exposure, but no randomized prospective trial has yet proven prevention of anthracycline cardiotoxicity.

Eligibility criteria

Inclusion Criteria:

* Adults ≥18 years.
* Histologically confirmed breast cancer with planned (neo)adjuvant anthracycline-based chemotherapy (4 cycles of epirubicin + cyclophosphamide or doxorubicin + cyclophosphamide).
* Eligible to start dapagliflozin or placebo prior to or at initiation of chemotherapy.
* Able to perform baseline echocardiography, vascular ultrasound (FMD and carotid stiffness), 6-minute walk test, and biomarker sampling.
* Willing and able to provide written informed consent.

Exclusion Criteria:

* Known heart failure (any prior diagnosis of HF).
* Clinically significant valvular heart disease.
* Prior exposure to chemotherapy or radiotherapy to the left chest.
* Type 1 diabetes mellitus.
* Symptomatic hypotension.
* History of recurrent urinary tract infections.
* History of diabetic ketoacidosis or ketonemia.
* Severe hepatic impairment (ALT, AST, ALP \>3× upper limit of normal).
* Severe renal impairment (eGFR \<20 mL/min/1.73 m²).
* Known allergy or intolerance to SGLT-2 inhibitors.
* Any use of SGLT-2 inhibitor therapy within 3 months prior to enrollment.
* Pregnancy or breastfeeding.
* Any condition that, in the investigator's judgment, could interfere with study participation, safety, or completion.

Where this trial is running

Ljubljana

• University Medical Centre Ljubljana — Ljubljana, Slovenia (Recruiting)

Study contacts

• Study coordinator: Jure Tršan

Conditions Heart Failure; Anthracycline-induced Cardiac Toxicity; Endothelial Function; Arterial Stiffness; Breast Cancer; Anthracycline-induced cardiac toxicity; Dapagliflozin; Cardio-Oncology