Cardiotoxicity in Breast Cancer Patients

September 16, 2025 updated by: Sara Mohamed Mohamed Abdel Motaleb, Helwan University

Evaluation of the Cardioprotective Effect of Dapagliflozin on Anthracyclines-Induced Cardiotoxicity in Breast Cancer Patients

The goal of this clinical trial is to learn if dapagliflozin drug has a cardioprotective effect against anthracyclines-induced cardiotoxicity. It will also learn about the safety of dapagliflozin drug.

Aim of the study:

Evaluate cardioprotective effect and safety of dapagliflozin against anthracyclines-induced cardiotoxicity.

The main questions it aims to answer are:

  1. Does the drug lower the cardiotoxicity which induced by anthracyclines?
  2. What medical problems do participants have when taking dapagliflozin drug?

Treatment

  1. Anthracyclines by 4 cycles included doxorubicin 50-60 mg/m2 with cyclophosphamide 600 mg as a combination or epirubicin 90-100 mg/m2 with cyclophosphamide 600 mg as a combination.
  2. Dapagliflozin 10 mg tablet orally, once daily. Started 7 days before the first cycle of anthracyclines till the end of last anthracyclines dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Breast cancer is a malignant tumor that originates in the cells of the breast tissue. It is the most common cancer in women worldwide, accounting for 24.2% of all cancer cases among women.

According to the latest World Health Organization statistics, there were an estimated 2.3 million new cases of breast cancer in 2020; it is the second leading cause of cancer death in women after lung cancer.

In Egypt, breast cancer is the most common malignancy in women, accounting for 38.8% of cancers in this population, with the estimated number of breast cancer cases nearly 22,700 in 2022 and forecasted to be approximately 46,000 in 2050.

Anthracyclines are well-established and highly effective anti-neoplastic agents, used to treat several adult and pediatric cancers, such as breast cancer, leukemia, lymphomas, sarcomas, and many others.

Anthracycline-induced cardiotoxicity typically manifests as a reduction in left ventricular ejection fraction (LVEF), cardiomyopathy, or symptomatic congestive heart failure (CHF).

Acute anthracycline cardiotoxicity - occurs during or immediately after a single dose of an anthracycline. It may manifest as ventricular dysfunction, ECG abnormalities and arrhythmias.

Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients.

In a recently published cohort study, 2000 cancer survivors were monitored over 7 years. The authors found that approximately one-third of deaths could be attributed to long-term cardiotoxicity.

The specific mechanisms of anthracycline cardiotoxicity by Oxidative stress, which in the presence of iron, generates reactive oxygen species that cause lipid peroxidation of the cell membrane leading to damage of the cardiomyocytes, inflammation by up-regulating the levels of various inflammatory mediators, including interleukin-1 and tumor necrosis factor-α in the heart, subsequently leading to cardiomyocyte damage, In addition, DOX activated the nod-like receptor pyrin domain containing 3 (NLRP3) in cardiomyocytes, promoting cardiomyocyte apoptosis and down-regulation of sirtuin and adenosine monophosphate-activated protein kinase (AMPK) activity which associated with cardiovascular disease by enhanced apoptosis and increased fibrosis. The cardiomyocyte has always been considered the main cellular target of anthracycline toxic effect in the heart, as their destruction results in the progressive development of cardiac dysfunction.

Since anthracyclines is known to cause cardiotoxicity as a side effect, a baseline echocardiogram (ECHO) is ordered for each patient before initiating anthracycline chemotherapy treatment as a standard of care. Additionally, follow-up ECHOs are conducted after starting the treatment cycles to detect any early signs of cardiotoxicity.

Sodium Glucose co-transport inhibitors (SGLT2i) have demonstrated significant cardioprotective effects beyond their glucose-lowering capabilities. Recent clinical studies have highlighted their ability to reduce cardiovascular events, such as heart failure and myocardial infarction, in diabetic patients.

The cardioprotective benefits are thought to arise from multiple mechanisms, including improved cardiac energy metabolism, reduced blood pressure, and decreased fluid overload. As a result, SGLT2i are emerging as a crucial therapeutic option not only for glycemic control but also for enhancing heart health, marking a promising advancement in the management of cardiovascular risks.

SGLT2i significantly reduces Systolic Blood Pressure (SBP) and arterial stiffness that leads to better oxygen consumption by myocardium and hence lowers the cardiac afterload. It also helps in reducing the body weight slightly. Additionally, dapagliflozin also contributes by lowering the plasma volume by diuresis i.e., the increased excretion of sodium and glucose in urine. Decreasing the inflammation pathway by modulating the activation of NLRP3 inflammasome, thereby attenuating the synthesis of proinflammatory cytokines and reduced levels of tumor necrosis factor-α and interleukins, decreasing oxidative Stress by attenuate the generation of reactive oxygen species and enhance antioxidant mechanisms by inhibiting NADPH oxidase (nicotinamide adenine dinucleotide phosphate hydrogen ) and enhance energy metabolism by up-regulating the expression or activity of AMPK and sirtuins.

In light of the demonstrated cardioprotective effects of SGLT2 inhibitors (SGLT2i) in heart failure patients, these agents have been integrated into standard heart failure clinical guidelines, irrespective of the patient's diabetic status. Considering the well-established cardiotoxicity associated with anthracycline use, a thorough literature review was conducted to explore the potential of SGLT2i as adjunctive therapy to mitigate cardiac toxicity in breast cancer patients undergoing anthracycline-based chemotherapy. However, the search yielded only preclinical evidence, which highlighted the promising role of dapagliflozin. Consequently, this clinical trial aims to evaluate the efficacy of dapagliflozin as adjunctive therapy in breast cancer patients receiving anthracyclines, with a specific focus on preventing or delaying the onset of cardiotoxicity.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Cairo Governorate
      • Cairo, Cairo Governorate, Egypt, 202
        • Recruiting
        • Al demerdash hospital at oncology departement
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. patients with pathologically proved invasive breast carcinoma.
  2. Patients were indicated for anthracyclines containing adjuvant chemotherapy or new adjuvant anthracyclines.
  3. Renal function (eGFR > 30 mL/minute per 1.73 m2 )
  4. LVEF is more than 50 %
  5. Age ≥ 18 and ≤ 60 years old

Exclusion Criteria:

  1. patients with any cardiac condition that contraindicate the use of anthracyclines, like heart failure, arrythmia, stroke and myocardial infarction.
  2. Previous anthracycline-containing regimens and any cardiotoxic chemotherapy regimens
  3. pregnant or breastfeeding patients
  4. patients receiving any other cardiotoxic agents.
  5. Patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.
  6. Mediastinal irradiation including heart.
  7. Refusal to sign the written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dapagliflozin group
Dapagliflozin group who consist of at least 20 breast cancer patients who receive 4 cycles of anthracyclines ( each cycle every 21 days ) with dapagliflozin 10 mg tablet once daily.
Drug: Dapagliflozin 10mg Tab

Dapagliflozin 10 mg tablet orally, once daily. Started 7 days before the first cycle of anthracyclines till the end of last anthracyclines dose.

taken orally, once daily. Started from 5 to 7 days before the first cycle of anthracyclines till the end of last anthracycline dose.

Other Names:
  • Dapablix 10 mg
No Intervention: Control group
Control group who consist of at least 20 breast cancer patients who receive 4 cycles of anthracyclines ( each cycle every 21 days ) only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
N-terminal pro-B-type natriuretic peptide (NT-pro BNP) testing
Time Frame: Baseline and after the last cycle of anthracyclines ( 0 and 2 to 3 months from baseline)
Monitoring the serum at Baseline and after the last cycle of anthracyclines. Changes in serum NT-Pro BNP from baseline will be calculated and compared between groups
Baseline and after the last cycle of anthracyclines ( 0 and 2 to 3 months from baseline)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Echocardiography by measuring left ventricular ejection fraction (LVEF)
Time Frame: a) Baseline b) After the last cycle of anthracyclines (approximately 2 to 3 months from baseline) c) 3 months after the end of chemotherapy (approximately 5 to 6 months from baseline) d) As needed for any symptomatic patients
LVEF (%) will be assessed using M-mode and 2D echocardiography performed by an experienced operator blinded to the patient's history. Changes in LVEF from baseline will be calculated and compared between groups at each time point.
a) Baseline b) After the last cycle of anthracyclines (approximately 2 to 3 months from baseline) c) 3 months after the end of chemotherapy (approximately 5 to 6 months from baseline) d) As needed for any symptomatic patients

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Helwan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2024

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

July 1, 2024

First Submitted That Met QC Criteria

July 1, 2024

First Posted (Actual)

July 9, 2024

Study Record Updates

Last Update Posted (Actual)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 16, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Dapagliflozin

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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