Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Change in left ventricular ejection fraction, as assessed by cardiac MRI
研究概览
简要总结
Women treated for breast cancer are at increased risk for cardiovascular disease, including heart failure. In this study, by using magnetic resonance imaging (MRI), the investigators want to assess if heart failure medications such as beta blockers and angiotensin receptor blockers can prevent cardiac dysfunction during early breast cancer therapy.
详细描述
Breast cancer is one of the most common malignancies in women. Recent progress in the detection and treatment of breast cancer has resulted in survival gains, but a consequence of therapeutic advances is an increasing number of long-term survivors who may be at risk for development of cardiovascular disease. Several studies suggest that women treated for breast cancer may be at increased risk for cardiovascular disease, the probable causes being multi-factorial. Importantly, therapies for breast cancer, including radiotherapy, anti-HER-2 regimens and certain chemotherapeutic regimens, may increase the risk of subsequent cardiovascular disease, including atherosclerotic disease, left ventricular dysfunction, and heart failure.
In the current study we propose to undertake a randomized, placebo-controlled, 2x2 factorial, double-blind trial to assess whether left ventricular dysfunction and/or injury is preventable, completely or partly, by the concomitant administration of the angiotensin receptor blocker (ARB), candesartan, and the beta blocker, metoprolol, during postoperative chemotherapy and radiotherapy.
The proposed study addresses an important clinical problem in a large patient group. Thus, the possibility of preventing cardiovascular side effects of contemporary therapy for breast cancer is important both clinically and scientifically.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-70 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Serum creatinine < 140 μmol/L or estimated creatinine clearance > 60 ml/min (using the modification of diet and renal disease (MDRD) formula)
- •Systolic blood pressure >= 110 mgHg and < 170 mmHg
- •LVEF >= 50%
排除标准
- •Hypotension, defined as systolic blood pressure < 110 mmHg
- •Bradycardia, defined as heart rate < 50 b.p.m.
- •Prior anthracycline chemotherapy regimen
- •Prior malignancy requiring chemotherapy or radiotherapy
- •Symptomatic heart failure
- •Systolic dysfunction (LVEF < 50%)
- •Clinically significant coronary artery disease, valvular heart disease, significant arrhythmias, or conduction delays.
- •Uncontrolled arterial hypertension defined as systolic blood pressure > 170 mm Hg
- •Treatment with ACEI, ARB or beta-blocker within the last 4 weeks prior to study start
- •Intolerance to ACEI, ARB or beta-blocker
- •Uncontrolled concomitant serious illness
- •Pregnancy or breastfeeding
- •Active abuse of drugs or alcohol
- •Suspected poor compliance
- •Inability to tolerate the MRI scanning protocol
研究组 & 干预措施
Metoprolol
Tablet, target dose 100 mg once daily
干预措施: Metoprolol (Drug)
Placebo for Metoprolol
Tablet, target dose 100 mg once daily
干预措施: Placebo (Drug)
Candesartan
Tablet, target dose 32 mg once daily
干预措施: Candesartan (Drug)
Placebo for Candesartan
Tablet, target dose 32 mg once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change in left ventricular ejection fraction, as assessed by cardiac MRI
时间窗: Baseline and end of study (up to 72 weeks)
次要结局
- Change in contrast enhancement by MRI(Baseline and approximately 4 weeks)
- Change in left 2D global strain, as assessed by echocardiography(Baseline and end of study (up to 72 weeks))
- Incidence of clinical of heart failure or objective left ventricular dysfunction(Up to 72 weeks)
- Change in biochemical markers of cardiac injury, i.e. hs-cTnT(Baseline and end of study (up to 72 weeks))
- Change in left ventricular diastolic function, as assessed by echocardiography(Baseline and end of study (up to 72 weeks))
- Change in biochemical markers of cardiac function, i.e. NT-proBNP(Baseline and end of study (up to 72 weeks))
- Change in contrast enhancement, as assessed by cardiac MRI(Baseline and end of study (up to 72 weeks))
研究者
Torbjorn Omland
Professor of Medicine
University Hospital, Akershus