Doxorubicin Induced CardiomyopathyPhase 2NCT06427226
Evaluation of the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity
A Phase 2 study testing Dapagliflozin 10mg Tab in people with Doxorubicin Induced Cardiomyopathy and Breast Cancer, run by Tanta University at 1 site in Egypt.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Doxorubicin Induced Cardiomyopathy, Breast Cancer
- What is being tested?
- Dapagliflozin 10mg Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteEgypt
- Study dates
- 31 Oct 2024to 1 Oct 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Osama M Ibrahim, Professor contact
Egypt1 site, 1 recruiting
- Recruiting
Medical Research Institute
Alexandria, Bab Sharqi, 21526
Sandy E Rezkallah, Bachelor, 01221065882, sandyehab58@gmail.com
Heba Elsheredy, Professor
About this study
Official title: Clinical Study to Evaluate the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients
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.
Read the detailed description
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
- Doxorubicin Induced Cardiomyopathy, Breast Cancer
- Being tested
- Dapagliflozin 10mg Tab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mg TabDrug
Dapagliflozin 10 mg tab once daily given during the duration of AC cycles.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | No intervention | 23 breast cancer patients which will receive four cycles of AC regimen (Doxorubicin and Cyclophosamide; each cycle is given every 21 days) only. |
| Dapagliflozin group | Active comparator | 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. Receives: Drug: Dapagliflozin 10mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of changes in ejection fraction using echocardiography
Initial evaluation of cardiac function by Echocardiography at baseline and after the end of chemotherapy. The primary outcome is to avoid reduction in patients' ejection fraction during doxorubicin administration.
Measured: Baseline and after the last AC cycle of chemotherapy (3months).
Secondary outcomes (2)
Change in Cardiac Troponin T level
Monitoring the serum biomarker Cardiac Troponin T at baseline and after the end of chemotherapy.
Measured: Baseline and after the last AC cycle of chemotherapy (3months).
Change in N-terminal pro-B-type natriuretic peptide level
Monitoring the serum biomarker NT-pro-BNP at baseline and after the end of chemotherapy.
Measured: Baseline and after the last AC cycle of chemotherapy (3months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2024
- Study start31 Oct 2024
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Doxorubicin Induced CardiomyopathyStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sandy Ehab Nabil Rezkallah, Tanta University
- Investigators
- Sandy E Rezkallah, bachelor, Principal investigator, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06427226
- Sponsor's protocol ID
- Dapagliflozin in breast cancer
- Status last verified
- Apr 2026
- First submitted
- 18 May 2024
- Last updated
- 17 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Belen E, Canbolat IP, Yigitturk G, Cetinarslan O, Akdeniz CS, Karaca M, Sonmez M, Erbas O. Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats. Eur Rev Med Pharmacol Sci. 2022 Jun;26(12):4403-4408. doi: 10.26355/eurrev_202206_29079.
PubMed 35776041Avula V, Sharma G, Kosiborod MN, Vaduganathan M, Neilan TG, Lopez T, Dent S, Baldassarre L, Scherrer-Crosbie M, Barac A, Liu J, Deswal A, Khadke S, Yang EH, Ky B, Lenihan D, Nohria A, Dani SS, Ganatra S. SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction. JACC Heart Fail. 2024 Jan;12(1):67-78. doi: 10.1016/j.jchf.2023.08.026. Epub 2023 Oct 25.
PubMed 37897456Chang WT, Lin YW, Ho CH, Chen ZC, Liu PY, Shih JY. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients. Arch Toxicol. 2021 Feb;95(2):659-671. doi: 10.1007/s00204-020-02951-8. Epub 2020 Nov 19.
PubMed 33211168
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Evaluate the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT06427226
- Acronym / sponsor ID
- Dapagliflozin in breast cancer
- Conditions
- Doxorubicin Induced Cardiomyopathy, Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 31 Oct 2024 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 23 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | No intervention | –23 breast cancer patients which will receive four cycles of AC regimen (Doxorubicin and Cyclophosamide; each cycle is given every 21 days) only. |
| Dapagliflozin group | Active comparator | Drug: Dapagliflozin 10mg Tab23 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10mg TabDapagliflozin 10 mg tab once daily given during the duration of AC cycles. | Drug | Dapagliflozin group |
Primary outcome
Assessment of changes in ejection fraction using echocardiography
Time frame: Baseline and after the last AC cycle of chemotherapy (3months).
Initial evaluation of cardiac function by Echocardiography at baseline and after the end of chemotherapy. The primary outcome is to avoid reduction in patients' ejection fraction during doxorubicin administration.
2 secondary outcomes
Change in Cardiac Troponin T level
Time frame: Baseline and after the last AC cycle of chemotherapy (3months).
Change in N-terminal pro-B-type natriuretic peptide level
Time frame: Baseline and after the last AC cycle of chemotherapy (3months).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Background: PubMed 35776041Belen E, Canbolat IP, Yigitturk G, Cetinarslan O, Akdeniz CS, Karaca M, Sonmez M, Erbas O. Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats. Eur Rev Med Pharmacol Sci. 2022 Jun;26(12):4403-4408. doi: 10.26355/eurrev_202206_29079.
- Background: PubMed 37897456Avula V, Sharma G, Kosiborod MN, Vaduganathan M, Neilan TG, Lopez T, Dent S, Baldassarre L, Scherrer-Crosbie M, Barac A, Liu J, Deswal A, Khadke S, Yang EH, Ky B, Lenihan D, Nohria A, Dani SS, Ganatra S. SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction. JACC Heart Fail. 2024 Jan;12(1):67-78. doi: 10.1016/j.jchf.2023.08.026. Epub 2023 Oct 25.
- Background: PubMed 33211168Chang WT, Lin YW, Ho CH, Chen ZC, Liu PY, Shih JY. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients. Arch Toxicol. 2021 Feb;95(2):659-671. doi: 10.1007/s00204-020-02951-8. Epub 2020 Nov 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Osama M Ibrahim, Professor contact
Sandy E Rezkallah, bachelor principal investigator
Tanta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin 10mg Tab in people with Doxorubicin Induced Cardiomyopathy and Breast Cancer, run by Tanta University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sandy Rezkallah, Bachelor (01221065882, sandyehab58@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of changes in ejection fraction using echocardiography (time frame: Baseline and after the last AC cycle of chemotherapy (3months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06427226, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.