Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography and by cardiac magnetic resonance imaging (CMR).
研究概览
简要总结
The investigators' objective is to assess the efficacy of the combined treatment with enalapril and carvedilol in the prevention of left ventricular systolic dysfunction in patients with hematological malignancies submitted to intensive chemotherapy with potential cardiotoxicity.
The hypothesis is that these drugs administered during chemotherapy may prevent left ventricular systolic dysfunction.
详细描述
The prognosis of patients with hematological malignancies has greatly improved in the last years with the use of new chemotherapeutic drugs and regimens at the cost of significant adverse events such as cardiac toxicity. Asymptomatic left ventricular systolic dysfunction limits the specific treatment of the patients and their long-term survival, since a significant proportion of them will relapse within 5 years after front-line therapy and will require further salvage treatment, including hematopoietic stem-cell transplantation in most instances.
Angiotensin-converting enzyme inhibitors (ACEIs) have showed to have preventive effects against chemotherapy-induced cardiotoxicity in animal models, and in patients with early cardiotoxicity. Carvedilol prevent free radical release, mitochondrial dysfunction, apoptosis, and dilated cardiomyopathy in animals treated with anthracyclines, and have shown promising results in preventing chemotherapy-induced left ventricular dysfunction in patients.
As demonstrated in post-infarction patients, the combined treatment with an ACEI and carvedilol could have additive effects to prevent LV dysfunction in patients with hematological malignancies at high risk of cardiac toxicity. Therefore, we designed the OVERCOME (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies) study, a prospective, randomized trial to evaluate the combined effect of enalapril and carvedilol on the prevention of left ventricular dysfunction in patients with malignant hemopathies undergoing intensive chemotherapy.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients 18-70 years old
- •Sinus rhythm
- •Normal LVEF (>=50%)
- •Patients recently diagnosed of acute leukemia to be submitted to intensive chemotherapy or
- •Patients with other hemopathies submitted to autologous peripheral blood stem cell transplantation
- •Signed informed consent
排除标准
- •Congestive heart failure
- •LVEF<50%
- •Coronary artery disease,
- •significant valvulopathy or myocardiopathy
- •Renal failure (MDRD<30)
- •Liver failure
- •Ongoing or expected need to be treated with angiotensin-converting enzyme inhibitors (ACE-i),angiotensin II receptor blockers (ARB) or beta-blockers
- •Prior allergy to ACEI or ARB
- •Systolic blood pressure <90 mmHg
- •Auriculoventricular (AV) block or sinus bradycardia (HR<60 bpm)
- •Persistent atrial fibrillation
- •Need to be treated with Class I antiarrhythmic drugs
- •Pregnancy
- •Inability or unwillingness to give unformed consent
研究组 & 干预措施
Enalapril and carvedilol
Enalapril 2.5 to 10 mg BID plus Carvedilol 6.25 to 25 mg BID
干预措施: Enalapril and carvedilol (Drug)
结局指标
主要结局
Change from baseline in left ventricular ejection fraction (LVEF) measured by echocardiography and by cardiac magnetic resonance imaging (CMR).
时间窗: 6 months after randomization
次要结局
- Prognostic value for cardiac toxicity of troponin I and BNP(up to 3 months)
- Incidence of death, heart failure or LV systolic disfunction (LVEF<45%)(6 months after randomization)
- Assessment of genetic polymorphisms involved in chemotherapy-induced cardiotoxicity(Baseline)
- Right and left ventricular volumes measured by CMR(6 months after randomization)
- Subgroup analysis by diagnosis (acute leukemia vs. other malignant hemopathies submitted to autologous peripheral blood stem cell transplantation), and positive biomarkers (TnI, BNP).(6 months after randomization)
- Incidence of an absolute decrease in LVEF>10 percent units associated with a decline below its normal limit of 50%(6 months after randomization)
- Serious adverse events(6 months after randomization)
- the incidence of LV dysfunction as assessed by the measurement of the LV strain, and of diastolic dysfunction measured by echo-Doppler(6 months after randomization)
研究者
Xavier Bosch
Dr.
Hospital Clinic of Barcelona