CardiotoxicityPhase 3LinagliptinNCT07852546
Cardioprotection Effect of Linagliptin
A Phase 3 study testing Doxorubicin and Empaglifloz 5 mg orally once daily in people with Cardiotoxicity, run by Tanta University at 1 site in Egypt.
Trial summary
1. Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cardiotoxicity
- What is being tested?
- Doxorubicin and Empaglifloz 5 mg orally once daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Oct 2026to 31 Dec 2028
- Phase
- Phase 3
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients aged ≥18 years.
- Egyptian nationality.
- Histologically confirmed breast cancer.
- Planned treatment with a doxorubicin-containing chemotherapy regimen.
- Expected cumulative doxorubicin dose of approximately ≥240 mg/m², or another prespecified protocol threshold.
- Baseline LVEF ≥53%.
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- Adequate baseline echocardiographic assessment.
- Baseline cardiac troponin below the laboratory's predefined exclusion threshold.
- Ability to take oral medication.
- Ability to provide written informed consent.
- Willingness to comply with study visits, blood sampling and cardiac assessments.
Who cannot join
- Previous exposure to anthracyclines.
- Known heart failure.
- Baseline LVEF <53%.
- Previous myocardial infarction or significant coronary artery disease.
- Significant valvular heart disease.
- Clinically significant arrhythmia.
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- Uncontrolled hypertension.
- Significant renal impairment according to a predefined eGFR threshold.
- Significant hepatic impairment.
- Active infection or another condition likely to affect troponin interpretation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mai Aboelyazed El-Gebaly, Associate Lecturer contact
Egypt1 site
Tanta University
Tanta, Elgharbeya, GHR
Mai Aboelyazed El-Gebaly, Associate Lecturer, 010-6141-2257 ext. 020, dr.mai.elgebaly@gmail.com
Mai Aboelyazed Elgebaly, Associate Lecturer, 011-1506-4114 ext. 020, dr.mai.elgebaly@gmail.com
About this study
Official title: Cardio-protective Effect of Linagliptin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy
- Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
Read the detailed description
- Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
The European Society of Cardiology recommends cardiovascular assessment and surveillance in patients receiving potentially cardiotoxic cancer therapies. Cardiac troponin (cTn) and natriuretic peptides may be used as biomarkers of cancer therapy-related cardiovascular toxicity, while echocardiography, including LVEF and global longitudinal strain (GLS) where available, provides complementary information about cardiac function.
Cardiac troponin is a highly specific biomarker of myocardial injury. According to the Fourth Universal Definition of Myocardial Infarction, myocardial injury is defined by a cardiac troponin concentration above the assay-specific 99th-percentile upper reference limit, while an acute injury is characterized by a rise and/or fall in troponin values.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are primarily used as glucose-lowering agents in patients with type 2 diabetes mellitus. Linagliptin is a selective DPP-4 inhibitor administered at a standard dose of 5 mg once daily. Large cardiovascular-outcome data have demonstrated cardiovascular safety of linagliptin in patients with type 2 diabetes at high cardiovascular and renal risk, including no significant increase in hospitalization for heart failure compared with placebo.
However, whether linagliptin can prevent anthracycline-associated myocardial injury in women with breast cancer without diabetes remains insufficiently established. This creates a clinically relevant research gap.
Therefore, the proposed study will investigate whether prophylactic linagliptin, administered during doxorubicin-containing chemotherapy, can attenuate biochemical evidence of myocardial injury assessed by cardiac troponin and reduce the development of cardiac dysfunction.
- Conditions
- Cardiotoxicity
- Being tested
- Doxorubicin, Empaglifloz 5 mg orally once daily
- Keywords
- Linagliptin, Doxorubicin
- Medical subject headings
- Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks
Empaglifloz 5 mg orally once dailyDrug
Initiated 1 week prior to chemotherapy; continued for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo Arm | Placebo comparator | Control Arm: Participants will receive standard oncological care without prophylactic linagliptin. Receives: Drug: Doxorubicin |
| Linagliptin Arm | Experimental | Participants will receive:
Linagliptin 5 mg orally once daily. The proposed treatment will begin before or at initiation of the first doxorubicin-containing chemotherapy cycle and continue throughout the predefined chemotherapy period. Receives: Drug: Doxorubicin; Drug: Empaglifloz 5 mg orally once daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Troponin Assessment
The principal biochemical endpoint will be defined as:
Cardiac troponin concentration >99th percentile upper reference limit of the laboratory assay.
Acute myocardial injury will be characterized by a dynamic rise and/or fall in troponin when clinically appropriate.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 Oct 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CardiotoxicityStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized, controlled, parallel-group, open-label clinical trial with blinded laboratory and cardiac imaging assessment.
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mai Abo Elyazeed Hassan Hamouda, Tanta University
- Investigators
- Haidy Mahmoud Sami, Lecturer, Study director, Delta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07852546
- Sponsor's protocol ID
- Delta University
- Acronym
- Linagliptin
- Status last verified
- Sep 2026
- First submitted
- 23 Sep 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be made available to other researchers. The study data will be maintained securely by the research team and will be accessible only to authorized study investigators. Participant confidentiality and privacy will be strictly protected, and data will not be shared in a form that could permit identification of individual participants.
Publications
Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138(20):e618-e651. doi:10.1161/CIR.0000000000000617. Osataphan N, Phrommintikul A, Leemasawat K, Somwangprasert A, Apaijai N, Suksai S, et al. Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial. Sci Rep. 2023;13:12759. doi:10.1038/s41598-023-40061-4. McGuire DK, Alexander JH, Johansen OE, Perkovic V, Rosenstock J, Cooper ME, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139(3):351-361. doi:10.1161/CIRCULATIONAHA.118.038352. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321(1):69-79. doi:10.1001/jama.2018.18249. Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol. 2010;28(25):3910-3916. doi:10.1200/JCO.2009.27.3615. Osataphan N, Phrommintikul A, Chattipakorn SC, Chattipakorn N. Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: insights for future interventions. J Cell Mol Med. 2020;24(12):6534-6557. doi:10.1111/jcmm.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardio-protective Effect of Linagliptin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy
- ClinicalTrials.gov ID
- NCT07852546
- Acronym / sponsor ID
- Linagliptin / Delta University
- Conditions
- Cardiotoxicity
- Keywords
- Linagliptin, Doxorubicin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Oct 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 1 Oct 2026 (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.
- Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
Detailed description
- Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
The European Society of Cardiology recommends cardiovascular assessment and surveillance in patients receiving potentially cardiotoxic cancer therapies. Cardiac troponin (cTn) and natriuretic peptides may be used as biomarkers of cancer therapy-related cardiovascular toxicity, while echocardiography, including LVEF and global longitudinal strain (GLS) where available, provides complementary information about cardiac function.
Cardiac troponin is a highly specific biomarker of myocardial injury. According to the Fourth Universal Definition of Myocardial Infarction, myocardial injury is defined by a cardiac troponin concentration above the assay-specific 99th-percentile upper reference limit, while an acute injury is characterized by a rise and/or fall in troponin values.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are primarily used as glucose-lowering agents in patients with type 2 diabetes mellitus. Linagliptin is a selective DPP-4 inhibitor administered at a standard dose of 5 mg once daily. Large cardiovascular-outcome data have demonstrated cardiovascular safety of linagliptin in patients with type 2 diabetes at high cardiovascular and renal risk, including no significant increase in hospitalization for heart failure compared with placebo.
However, whether linagliptin can prevent anthracycline-associated myocardial injury in women with breast cancer without diabetes remains insufficiently established. This creates a clinically relevant research gap.
Therefore, the proposed study will investigate whether prophylactic linagliptin, administered during doxorubicin-containing chemotherapy, can attenuate biochemical evidence of myocardial injury assessed by cardiac troponin and reduce the development of cardiac dysfunction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, randomized, controlled, parallel-group, open-label clinical trial with blinded laboratory and cardiac imaging assessment.
| Arm | Type | Receives |
|---|---|---|
| Placebo Arm | Placebo comparator | Drug: DoxorubicinControl Arm: Participants will receive standard oncological care without prophylactic linagliptin. |
| Linagliptin Arm | Experimental | Drug: Doxorubicin, Drug: Empaglifloz 5 mg orally once dailyParticipants will receive: Linagliptin 5 mg orally once daily. The proposed treatment will begin before or at initiation of the first doxorubicin-containing chemotherapy cycle and continue throughout the predefined chemotherapy period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Female patients aged ≥18 years.
- Egyptian nationality.
- Histologically confirmed breast cancer.
- Planned treatment with a doxorubicin-containing chemotherapy regimen.
- Expected cumulative doxorubicin dose of approximately ≥240 mg/m², or another prespecified protocol threshold.
Key exclusion criteria (10 listed)
- Previous exposure to anthracyclines.
- Known heart failure.
- Baseline LVEF <53%.
- Previous myocardial infarction or significant coronary artery disease.
- Significant valvular heart disease.
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 |
|---|---|---|
| DoxorubicinStandard oncologic care without cardioprotective intervention followed concurrently for 24 weeks | Drug | Linagliptin Arm, Placebo Arm |
| Empaglifloz 5 mg orally once dailyInitiated 1 week prior to chemotherapy; continued for 24 weeks | Drug | Linagliptin Arm |
Primary outcome
Cardiac Troponin Assessment
Time frame: 3 months
The principal biochemical endpoint will be defined as: Cardiac troponin concentration >99th percentile upper reference limit of the laboratory assay. Acute myocardial injury will be characterized by a dynamic rise and/or fall in troponin when clinically appropriate.
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 15 Oct 2026.
- BackgroundLyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138(20):e618-e651. doi:10.1161/CIR.0000000000000617. Osataphan N, Phrommintikul A, Leemasawat K, Somwangprasert A, Apaijai N, Suksai S, et al. Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial. Sci Rep. 2023;13:12759. doi:10.1038/s41598-023-40061-4. McGuire DK, Alexander JH, Johansen OE, Perkovic V, Rosenstock J, Cooper ME, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139(3):351-361. doi:10.1161/CIRCULATIONAHA.118.038352. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321(1):69-79. doi:10.1001/jama.2018.18249. Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol. 2010;28(25):3910-3916. doi:10.1200/JCO.2009.27.3615. Osataphan N, Phrommintikul A, Chattipakorn SC, Chattipakorn N. Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: insights for future interventions. J Cell Mol Med. 2020;24(12):6534-6557. doi:10.1111/jcmm.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be made available to other researchers. The study data will be maintained securely by the research team and will be accessible only to authorized study investigators. Participant confidentiality and privacy will be strictly protected, and data will not be shared in a form that could permit identification of individual participants.
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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.
Mai Aboelyazed El-Gebaly, Associate Lecturer contact
Haidy Mahmoud Sami, Lecturer study director
Delta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxorubicin and Empaglifloz 5 mg orally once daily in people with Cardiotoxicity, 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 11 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: opening soon, as of the sponsor's last update on 15 Oct 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Mai Aboelyazed El-Gebaly, Associate Lecturer (+0201061412257 ext. 020, dr.mai.elgebaly@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac Troponin Assessment (time frame: 3 months). 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 NCT07852546, which also lists 1 linked publication.
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 15 Oct 2026.