Effect of Levosimendan or Placebo on Exercise Capacity and Hemodynamics in Patients With Advanced Chronic Heart Failure (LOCO-CHF Trial)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- ΔCO/PCWP (submax)
研究概览
简要总结
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic heart failure.
Hypothesis: Treatment with 6 hours infusion of levosimendan compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. 42 consecutive patients who meet the eligibility criteria will be enrolled.
详细描述
Background: Patients with advanced heart failure (HF) symptoms (NYHA III-IV) have poor quality of life and significantly impaired functional capacity despite optimal medical management. Exercise intolerance in HF results from multiple pathophysiological processes, but central hemodynamics during exercise are important determinants. In patients with advanced HF, intermittent levosimendan infusion is sometimes used to relieve symptoms and possibly improve prognosis. A short-term effect of levosimendan infusion on exercise capacity has previously been reported. However, the underlying mechanisms behind such an improvement, as well as more durable effects of levosimendan on exercise capacity in advanced chronic HF, have not been clearly established. Also the hemodynamic effect of levosimendan has not been investigated in advanced chronic HF during exercise.
To our knowledge no previous studies have evaluated the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics in patients with advanced chronic HF. This study will hopefully improve the understanding of the role of levosimendan in the management of these patients.
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic HF.
Hypothesis
Treatment with 6 hours infusion of levosimendan 0.2 µg/kg/min compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP (Day 0 to Day 5 (4-6) after infusion) in patients with advanced chronic HF.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. The study population will consist of 42 consecutive patients who meet the eligibility criteria. Patients will be randomized 1:1 to treatment with either levosimendan or placebo.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study is double-blinded; hence neither patients nor investigators are aware of the treatment assignment throughout the study period. 2 unblinded study nurses at each site will perform randomization and prepare study medication blinded to the rest of the research team.
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •NYHA III-IV on optimal medical treatment
- •LVEF ≤35%
- •NT-proBNP >600 µg/L
- •pVO2 <20 mL/kg/min
- •No hospitalization for HF or change in loop diuretic <2 weeks
排除标准
- •Recent or acute coronary and respiratory syndromes
- •Recent sustained ventricular tachycardia or ventricular fibrillation
- •Severe aortic or mitral valve disease
- •Known malfunctioning artificial heart valve
- •Uncorrected obstructive valvular disease
- •Hypertrophic cardiomyopathy
- •Fertile women
- •Uncorrected thyroid disease
- •Presence of any disease/condition that might per se influence exercise performance
- •Left ventricular assist device
- •Pacemaker-guided heart rate at rest or during exercise
- •Known contraindication for treatment with levosimendan
- •Any treatment with levosimendan in the previous 6 months
- •Inability to perform a VO2max test
- •Symptomatic hypotension or systolic blood pressure < 90 mmHg
研究组 & 干预措施
Levosimendan
Study participants in this arm will receive a 6 hours infusion of levosimendan 0.2 µg/kg/min.
干预措施: Levosimendan (Drug)
Placebo
Study participants in this arm will receive a 6 hours infusion of placebo (sterile isotonic sodium chloride + 5% dextrose + vitamin B)
干预措施: Placebo (Drug)
结局指标
主要结局
ΔCO/PCWP (submax)
时间窗: Day 0 to Day 5 (4-6)
Change in CO/PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at the workload corresponding to 50% of pVO2 determined at baseline
次要结局
- SvO2 maximal(Day 5)
- Workload maximal(Day 5)
- ΔCO/PCWP (peak)(Day 0 to Day 5 (4-6))
- ΔCO (peak)(Day 0 to Day 5 (4-6))
- ΔPCWP (rest)(Day 0 to Day 5 (4-6))
- ΔCO (rest)(Day 0 to Day 5 (4-6))
- ΔCVP (rest)(Day 0 to Day 5 (4-6))
- ΔmPA (rest)(Day 0 to Day 5 (4-6))
- ΔSvO2 (rest)(Day 0 to Day 5 (4-6))
- Δ6MWT day 3(Day 0 to Day 3)
- Δ6MWT day 5 (4-6)(Day 0 to Day 5 (day 4-6))
- Δ6MWT day 14(Day 0 to Day 14)
- ΔNT-proBNP day 3(Day 0 to Day 3)
- ΔNT-proBNP day 5(Day 0 to Day 5 (day 4-6))
- ΔNT-proBNP day 14(Day 0 to Day 14)
- ΔPCWP (peak)(Day 0 to Day 5 (4-6))
- CO maximal(Day 5)
- PCWP maximal(Day 5)
- QOL day 3(Day 3)
- QOL day 5(Day 5)
- QOL Day 14(Day 14)
研究者
Finn Gustafsson
MD, PhD, DMSci, Professor of Cardiology
Rigshospitalet, Denmark