Evaluation of the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2025-08-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a randomized controlled clinical trial that aims to evaluate the safety and efficacy of Dapagliflozin as a cardioprotective in doxorubicin-induced cardiotoxicity in breast cancer patients.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Cardiotoxicity in Breast Cancer Patients

NCT06491680

Breast Cancer

RECRUITING PHASE4

Effect of DAPAglifozin on MYOcardial Remodeling of Breast CANCER Patients Treated with Anthracycline Based Chemotherapy

NCT06711185

Breast Cancer

RECRUITING PHASE3

Clinical Study to Evaluate The Cardioprotective Effect of Pentoxifylline Against Doxorubicin Induced Cardiotoxicity in Breast Cancer Patients

NCT07137793

Doxorubicin Induced Cardiotoxicity Breast Cancer

RECRUITING PHASE2

CardioPROTECTion with Dapagliflozin in Breast Cancer Patients Treated with AnthrAcycline - PROTECTAA TRIAL

NCT06304857

Breast Cancer Heart Failure

RECRUITING PHASE3

Potential Protective Role of SGLT-2 Inhibitors for Chemotherapy-induced Cardiotoxicity

NCT06341842

Breast Cancer

RECRUITING PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Breast cancer is the most common type of cancer in women and the first cause of cancer death among them. In Egypt, it represents 33%of female cancer cases and more than 22,000 new cases are diagnosed each year. This is expected to rise exponentially over the next years given the enlarging population and changes in the population pyramid.

The Early Breast Cancer "Trialists" Collaborative Group (EBCTCG) reported that the inclusion of anthracyclines as doxorubicin in the management of breast cancer improved absolute survival by approximately 3% at 5 years and 4% at 10 years. Therefore, anthracyclines remain the cornerstone of treatment for breast cancer patients.

Despite its effectiveness, doxorubicin is associated with cumulative, dose-dependent, and potential cardiotoxicity.

Although the main mechanism of doxorubicin-induced cardiotoxicity has not been fully known, there are several mechanisms proposed for cardiac injury including oxidative stress, free radical generation, and apoptosis are most widely reported. Other mechanisms are also involved such as impaired mitochondrial function, perturbation in iron regulatory protein, disruption of Ca2+ homeostasis, autophagy, and the release of nitric oxide and inflammatory mediators.

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a class of glucose-lowering agents and is used to treat patients with type 2 diabetes. Besides reducing glucose reabsorption, DAPA has shown protective effects on cardiovascular diseases. The cardioprotective effects of DAPA have been demonstrated in patients with diabetic cardiomyopathy, heart failure (HF) with preserved ejection fraction (EF), and HF with reduced EF. SGLT2 inhibitors exert their cardioprotective effect by increasing energy metabolism, mitochondrial biogenesis, autophagy, and ketone bodies while decreasing endoplasmic reticulum (ER) stress, ferroptosis, oxidative stress, and inflammation.

In a recent animal study, DAPA protected against doxorubicin-induced cardiotoxicity by reducing ER stress, as evidenced by the decreased expression of the ER-related proteins including glucose-regulated protein 78, protein kinase R-like endoplasmic reticulum kinase and transcription factor 4.

Doxorubicin administration have been shown to increase HF incidence, HF admissions, and the development of cardiomyopathy which is defined by a decline in left ventricle ejection fraction and these outcomes were attenuated by SGLT2 inhibitors.

It is known that doxorubicin increases the circulating level of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) which DAPA significantly reduced in a recent animal study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Doxorubicin Induced Cardiomyopathy Breast Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Control Group

23 breast cancer patients which will receive four cycles of AC regimen (Doxorubicin and Cyclophosamide; each cycle is given every 21 days) only.

Group Type NO_INTERVENTION

No interventions assigned to this group

Dapagliflozin group

23 breast cancer patients which will receive four cycles of AC regimen (Doxorubicin and Cyclophosamide; each cycle is given every 21 days) plus Dapagliflozin 10 mg once daily.

Group Type ACTIVE_COMPARATOR

Dapagliflozin 10mg Tab

Intervention Type DRUG

Dapagliflozin 10 mg tab once daily given during the duration of AC cycles.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Dapagliflozin 10mg Tab

Dapagliflozin 10 mg tab once daily given during the duration of AC cycles.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Age ≥18 years old.
* Chemo-naïve patients with biopsy confirmed diagnosis of breast cancer and with stage I-III breast cancer according to the American Joint Committee on Cancer (TNM staging system of breast cancer).
* Patients intended to receive at least 4 cycles of doxorubicin or more.
* Patients with performance status \<2 according to Eastern Cooperative Oncology Group (ECOG) score.
* Echocardiographic LVEF ≥55%.
* Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 ×109/L, platelet count ≥ 90 × 109/L and hemoglobin level ≥ 10 g/dl).
* Patients with adequate liver function and adequate renal function.
* Signed informed consent to participate in the study.

Exclusion Criteria

* Age \<18 years old and \>65 years old.
* Patients with prior exposure to anthracyclines within the last 6 months.
* Patients with evidence of metastasis at initial assessment.
* Treatment with any SGLT-2 inhibitors for 6 months prior to the screening.
* Patients taking any other cardioprotective medications.
* Pregnancy and breast feeding.
* Alcohol abuse.
* History of heart failure or LVEF \<50%.
* Presence of any cardiac-related conditions such as angina pectoris, valvular disease, uncontrolled systemic hypertension, coronary heart disease, and cardiac surgery within the last 3 months.
* Patients with type 1 diabetes mellitus or diabetic ketoacidosis, history of stroke, and patients with severe renal impairment with GFR \<25ml/min/1.73m2 . - Patients taking gatifloxacin as it causes major drug interaction with dapagliflozin.

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No