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

NCT07245069 | Recruiting Phase 2 DMC

• 1 other identifier: 0120-383/2024-2711-3
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized, double-blind, placebo-controlled clinical trial is to determine whether dapagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, can help prevent anthracycline-induced cardiotoxicity caused by anthracycline chemotherapy in adult women with breast cancer receiving (neo)adjuvant treatment. The main questions the study aims to answer are: i) Does dapagliflozin reduce the decline in left ventricular function (measured by LVEF, GLS, and myocardial work) during and after anthracycline therapy? ii) Does dapagliflozin lessen the deteriorating effect of chemotherapy on endothelial function and arterial stiffness? iii) Does dapagliflozin effect levels of cardiac injury and inflammation biomarkers (e.g., hs-troponin T, NT-proBNP, ST-2, GDF-15, galectin-3, IL-6, MPO)? Researchers will compare dapagliflozin 10 mg daily with placebo to see whether those receiving dapagliflozin experience less heart and vascular impairment during treatment. Participants will:

• Take either dapagliflozin or placebo once daily during anthracycline chemotherapy.
• Undergo heart and vascular ultrasound, and a 6-minute walk test before chemotherapy and again at 24 and 52 weeks.
• Provide blood samples before, during and after chemotherapy to measure cardiac biomarkers.
• Complete multiple questionnaires on quality of life.

Conditions

Heart Failure; Anthracycline-induced Cardiac Toxicity; Endothelial Function (FMD); Arterial Stiffness; Breast Cancer

Keywords

Anthracycline-induced cardiac toxicity; Dapagliflozin; Breast Cancer; Cardio-Oncology; Primary Prevention; Global Longitudinal Strain; Myocardial Work; Endothelial Function; Flow-Mediated Dilation; Pulse Wave Velocity; Troponin; NT-proBNP; Heart Failure; Inflammation; Sodium-Glucose Transporter 2 Inhibitors

Outcome Measures

Primary Outcomes (2)

• Change in Global Longitudinal Strain (GLS)

  Global Longitudinal Strain (GLS), measured using speckle-tracking echocardiography in three apical views, will be used to quantify subclinical left ventricular systolic dysfunction. The primary endpoint is the change in GLS from baseline to 24 and 52 weeks. A relative worsening of \>15% is considered clinically meaningful.

  52 weeks

• Change in Flow-Mediated Dilation (FMD) of the Brachial Artery

  Endothelial function will be assessed by ultrasound measurement of flow-mediated dilation (FMD) of the brachial artery after forearm cuff occlusion. The endpoint is the absolute change in FMD (%) from baseline to 24 weeks. A reduction \>2 absolute percentage points will be considered clinically meaningful. FMD will also be measured at 52 weeks to characterize the sustained effect of dapagliflozin on endothelial function compared with placebo.

  52 weeks

Secondary Outcomes (6)

• Change in Cardiovascular and Inflammatory Biomarkers

  52 weeks

• Change in Health-Related Quality of Life (EQ-5D Index Score)

  52 weeks

• Change in Left Ventricular Ejection Fraction (LVEF)

  52 weeks

• Change in Carotid Arterial Stiffness (Pulse Wave Velocity and Stiffness Index β)

  52 weeks

• KCCQ (Kansas City Cardiomyopathy Questionnaire)

  52 weeks

Study Arms (2)

Dapagliflozin 10 mg Daily

EXPERIMENTAL

Participants randomized to this arm will receive dapagliflozin 10 mg orally once daily for a total duration of 52 weeks (1 year). Study medication will begin before or at the start of anthracycline chemotherapy and will continue throughout chemotherapy and the post-treatment follow-up period, according to protocol.

Drug: Dapagliflozin 10 mg

Placebo

PLACEBO COMPARATOR

Participants randomized to this arm will receive a matching placebo orally once daily for a total duration of 52 weeks (1 year). Placebo will be initiated before or at the start of anthracycline chemotherapy and continued throughout chemotherapy and the 1-year protocol-defined follow-up period.

Drug: Placebo

Interventions

Dapagliflozin 10 mg DRUG

Forgixa® 10 mg daily

Dapagliflozin 10 mg Daily

Placebo DRUG

Lactose tablet daily

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

MeSH Terms

Conditions

Heart Failure; Breast Neoplasms; Inflammation

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jure Tršan

CONTACT

Slovenia; jure.trsan@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

SL (1)