Efficacy and Safety of Pulsed Infusions of Levosimendan in Outpatients With Advanced Heart Failure - A Multicenter, Double-blind, Placebo Controlled Prospective Trial With Two Arms
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 120
- 试验地点
- 11
- 主要终点
- proportion of patients showing an improvement in the six-minutes walk test and a higher scoring in the Kansas City Cardiomyopathy Questionnaire (KCCQ)
研究概览
简要总结
The purpose of this study is to compare the effects of a pulsed application of Levosimendan versus placebo on the composite end-point functional capacity and quality of life.
详细描述
BACKGROUND Significant advances have been made in the treatment of congestive heart failure (CHF) in the past few years. Neurohumoral therapy with ACE-inhibitors, ß-blockers and aldosterone antagonists has been established to significantly reduce morbidity and mortality. However, despite the advances of modern therapy advanced CHF remains a syndrome with a poor prognosis. Additionally, this syndrome is associated with poor quality of life and leads to progressive debiliation and cardial cachexia. Repeat hospitalizations for acute heart failure are common among severe CHF patients. Besides the discomfort for the patients hospital admissions constitute the lion's share of the health expenditure for the heart failure syndrome.
Inotropic support is provided to patients suffering acute heart failure refractory to neurohumoral therapy. This approach is performed according to the AHA/ACC- as well as to ESC Guidelines for therapy of CHF. Inotropic therapy is targeted on hemodynamic stabilization, improvement of functional status, and reduction of rehospitalization.
Moreover, in many centres treatment with inotropes such as dobutamine and milrinone are an integral part of the applied bridge to transplant concept in severe heart failure patients. In fact, continuous or pulsed inotropic support in severe heart failure patients has been tested repeatedly in small clinical studies.
Intermittent ambulatory low dose administration of dobutamine versus conventional therapy did not improve functional capacity in the DICE-Trial. By contrast, several case series with different dose regimens of dobutamine indicated improvement of functional status.
TRIAL RATIONALE Based on its pharmacologic profile Levosimendan appears to be promising in the treatment of severe chronic heart failure functional NYHA class III/IV to improve quality of life and physical activity and to reduce hospital admissions for acute heart failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with chronic stable heart failure NYHA III and IV diagnosed at least 3 months before inclusion
- •6-min.-walk-test < 350 meters
- •EF < 35 %
- •Age > 20 years
- •Optimized and individualised neurohormonal background therapy according to ESC-guidelines for the treatment of chronic heart failure.
- •Patient has signed informed consent
排除标准
- •Hospitalization for decompensated heart failure requiring i.v. diuretics within the last month before randomization
- •History of torsades des pointes
- •Allergy to Levosimendan or any of the excipients
- •Administration of inotropes in the last 4 weeks
- •Potassium <3,5 and >5,5 mmol/l
- •Systolic blood pressure <= 100 mmHg
- •Women at childbearing age without using effective contraceptives ( oral contraceptives, intrauterine contraceptive devices) unless surgical sterilisation has been undertaken.
- •Female patients who are pregnant or nursing
- •Creatinin Clearance < 30ml/min/m2
- •Severe anemia (Hb < 10 mg /dl)
- •Mechanical obstruction affecting the ventricular filling or the outflow or both
- •Patients with non compliance
- •Severe conditions, which make the patient unsuitable to participate in a study as judged by the investigator
- •Severe liver disease
- •Percutaneous coronary intervention within the last 1 months
- •Coronary bypass surgery within the last 3 months
- •Planned HTX within the next six months
- •Patient involved in another clinical trial
- •De-nove heart failure
研究组 & 干预措施
Levosimendan
Chronic stable heart failure
干预措施: Levosimendan (Drug)
Placebo
Chronic Stable Heart Failure
干预措施: Placebo (Drug)
结局指标
主要结局
proportion of patients showing an improvement in the six-minutes walk test and a higher scoring in the Kansas City Cardiomyopathy Questionnaire (KCCQ)
时间窗: 24 weeks
次要结局
- effects of a pulsed application of levosimendan on event free survival(24 weeks from randomization)