Cardio-protective Effect of Linagliptin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy
| Registry | NCT07852546, acronym Linagliptin |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 3 |
| Study type | Interventional; randomized, parallel, masking: none, prevention |
| Enrollment | 140 (Estimated) |
| Sponsor | Tanta University (Other) |
| Conditions | Cardiotoxicity |
| Interventions | Doxorubicin, Empaglifloz 5 mg orally once daily (Drug) |
| Dates | start 2026-10-01 (estimated), primary completion 2028-10-31 (estimated), completion 2028-12-31 (estimated), first posted 2026-10-01, last updated 2026-10-15 |
| Locations | 1 site in Egypt |
Related Papers Related Patents Related Grants Related Experts
AI Assistant Save
All trials for Cardiotoxicity All trials of Doxorubicin All trials of Empaglifloz 5 mg orally once daily
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.
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.
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Placebo Arm | Placebo comparator | Drug: Doxorubicin | Control Arm: Participants will receive standard oncological care without prophylactic linagliptin. |
| Linagliptin Arm | Experimental | Drug: Doxorubicin; Drug: Empaglifloz 5 mg orally once daily | 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. |
Sex: Female, ages: 18 Years to any
Inclusion Criteria: * 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%. * 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. Exclusion Criteria: * 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. * Uncontrolled hypertension. * Significant renal impairment according to a predefined eGFR threshold. * Significant hepatic impairment. * Active infection or another condition likely to affect troponin interpretation.
| Facility | City | Country | Status |
|---|---|---|---|
| Tanta University | Tanta, Elgharbeya | Egypt |