Clinical Study to Evaluate the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Assessment of changes in ejection fraction using echocardiography
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Dapagliflozin 10mg Tab (Drug)
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.
结局指标
主要结局
Assessment of changes in ejection fraction using echocardiography
时间窗: 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.
次要结局
- Change in Cardiac Troponin T level(Baseline and after the last AC cycle of chemotherapy (3months).)
- Change in N-terminal pro-B-type natriuretic peptide level(Baseline and after the last AC cycle of chemotherapy (3months).)
研究者
Sandy Ehab Nabil Rezkallah
Principle investigator
Tanta University