Effects of Empagliflozin Versus Metformin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy: A Prospective Randomized Controlled Cardio-Oncology Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- LVEF (Left ventricular ejection fraction) : The left ventricular drain fraction or the amount of blood pumped from the left ventricle with each contraction.
研究概览
简要总结
Background: Doxorubicin (DOX) remains a cornerstone in adjuvant and neoadjuvant therapy for breast cancer, but its utility is hindered by dose-dependent cardiotoxicity. Both SGLT2 inhibitors (Empagliflozin) and Biguanides (Metformin) have demonstrated off-target cardioprotective and metabolic properties in preclinical and clinical settings.
Objective: To compare the cardioprotective efficacy, safety, and metabolic/oncologic outcomes of Empagliflozin versus Metformin in non-diabetic or controlled-diabetic women with breast cancer undergoing doxorubicin-based chemotherapy.
Design: Prospective, 3-arm, open-label (or double-blind), randomized controlled clinical trial (RCT).
Duration: 18 months
详细描述
Background & Rationale Anthracyclines, primarily Doxorubicin, induce cardiotoxicity through reactive oxygen species (ROS) accumulation, topoisomerase II-beta inhibition, mitochondrial dysfunction, and cardiomyocyte apoptosis.
- Empagliflozin (SGLT2 inhibitor): Reduces oxidative stress, attenuates cardiac inflammation, improves myocardial energy bioenergetics, and prevents adverse left ventricular remodeling independently of glycemic status.
- Metformin (AMPK activator): Restores autophagic flux, preserves mitochondrial membrane potential, reduces ROS production, and exhibits anti-tumor proliferation effects.
- Gaps in Knowledge: While both drugs individually show promise against anthracycline-induced cardiotoxicity (AIC), direct head-to-head clinical trials comparing an SGLT2i versus Metformin during active anthracycline treatment are lacking.
3. Study Hypothesis
- Primary Hypothesis: Prophylactic administration of Empagliflozin or Metformin significantly attenuates the subclinical decline in Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS) compared to standard care in women receiving doxorubicin.
- Secondary Hypothesis: Empagliflozin demonstrates superior reduction in cardiac biomarker elevation (hs-cTnI, NT-proBNP) and microvascular strain compared to Metformin.
4. Study Objectives Primary Objective To compare the changes in left ventricular systolic function (measured via baseline to 6-month Echocardiographic GLS and LVEF) among the Empagliflozin group, Metformin group, and Control group.
Secondary Objectives
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
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult females (≥18 years) with histologically confirmed breast cancer.
- •Scheduled to receive doxorubicin-based chemotherapy regimens (e.g., AC regimen: Doxorubicin + Cyclophosphamide every 2 or 3 weeks for 4 cycles).
- •Baseline LVEF ≥ 55 on transthoracic echocardiography with normal baseline GLS.
- •Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2
- •Written informed consent provided
排除标准
- •Prior exposure to anthracyclines, mediastinal radiation, or anti-HER2 therapy.
- •Pre-existing heart failure, coronary artery disease, or LVEF $< 55\%$.
- •Uncontrolled Type 2 Diabetes Mellitus (HbA1c $> 8.5\%$) or Type 1 Diabetes Mellitus.
- •Severe renal impairmet (eGFR < 45 mL/min/1.73 m2) or hepatic dysfunction.
- •History of recurrent Urinary Tract Infections (UTIs), genital mycotic infections, or ketoacidosis (for Empagliflozin safety).
- •Hypersensitivity to Empagliflozin or Metformin.
研究组 & 干预措施
Arm A (Control)
Standard oncologic care without cardioprotective intervention followed concurrently for 12 weeks
Arm B (Empaglflozin)
Empagliflozin 10 mg orally once daily initiated 1 week prior to chemotherapy; continued for 12 weeks
干预措施: Empagliflozin (EMPA) (Drug)
Arm C (Metformin)
Metformin 500 mg orally twice daily (escalated to 1000 mg twice daily as tolerated) initiated 1 week prior to chemotherapy; continued for 12 weeks
干预措施: Metformin (Drug)
结局指标
主要结局
LVEF (Left ventricular ejection fraction) : The left ventricular drain fraction or the amount of blood pumped from the left ventricle with each contraction.
时间窗: 6 months
LVEF from baseline (T0) to 6-month follow-up (T3), measured by 2D Speckle-Tracking Echocardiography.
次要结局
未报告次要终点
研究者
Mai Abo Elyazeed Hassan Hamouda
Associate Lecturer
Tanta University