Cardioprotection Effect of Linagliptin

NCT07852546 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: Delta University
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cardiotoxicity

Keywords

Linagliptin; Doxorubicin

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Study Arms (2)

Arm A (Control)

PLACEBO COMPARATOR

Participants will receive standard oncological care without prophylactic linagliptin.

Drug: Doxorubicin

Arm B (Linagliptin)

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.

Drug: Doxorubicin; Drug: Empaglifloz 5 mg orally once daily

Interventions

Doxorubicin DRUG

Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks

Arm A (Control); Arm B (Linagliptin)

Empaglifloz 5 mg orally once daily DRUG

Initiated 1 week prior to chemotherapy; continued for 24 weeks

Arm B (Linagliptin)

Eligibility Criteria

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

You may qualify if:

• \. Female patients aged ≥18 years. 2. Egyptian nationality. 3. Histologically confirmed breast cancer. 4. Planned treatment with a doxorubicin-containing chemotherapy regimen. 5. Expected cumulative doxorubicin dose of approximately ≥240 mg/m², or another prespecified protocol threshold.
• \. Ability to take oral medication. 10. Ability to provide written informed consent. 11. Willingness to comply with study visits, blood sampling and cardiac assessments.

You may not qualify if:

• \. Previous exposure to anthracyclines. 2. Known heart failure. 3. Baseline LVEF \<53%. 4. Previous myocardial infarction or significant coronary artery disease. 5. Significant valvular heart disease. 6. Clinically significant arrhythmia. 7. Uncontrolled hypertension. 8. Significant renal impairment according to a predefined eGFR threshold. 9. Significant hepatic impairment. 10. Active infection or another condition likely to affect troponin interpretation.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta University

Tanta, Elgharbeya, GHR, Egypt

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

Cardiotoxicity

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Haidy Mahmoud Sami, Lecturer

  Delta University

  STUDY DIRECTOR

Central Study Contacts

Mai Aboelyazed El-Gebaly, Associate Lecturer

CONTACT

+0201061412257; dr.mai.elgebaly@gmail.com

Mai Aboelyazed Elgebaly, Associate Lecturer

CONTACT

+201115064114; dr.mai.elgebaly@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Because linagliptin administration is readily identifiable, the study will be open-label with respect to patients and treating investigators. However: * Laboratory personnel assessing cardiac troponin should be blinded to treatment allocation. * Echocardiographers should be blinded whenever feasible. * Statistical analysis should be performed using coded treatment groups. * Adjudication of cardiac outcomes should preferably be performed by investigators blinded to treatment assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Lecturer

Model Details: Prospective, randomized, controlled, parallel-group, open-label clinical trial with blinded laboratory and cardiac imaging assessment.

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: October 1, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)