Effect of Levosimendan or Placebo on Exercise in Advanced Chronic Heart Failure
- Registration Number
- NCT03576677
- Lead Sponsor
- Finn Gustafsson
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 42
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Study participants in this arm will receive a 6 hours infusion of placebo (sterile isotonic sodium chloride + 5% dextrose + vitamin B) Levosimendan Levosimendan Study participants in this arm will receive a 6 hours infusion of levosimendan 0.2 µg/kg/min.
- Primary Outcome Measures
Name Time Method ΔCO/PCWP (submax) 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
- Secondary Outcome Measures
Name Time Method SvO2 maximal Day 5 Maximal SvO2 at Day 5 (day 4-6)
Workload maximal Day 5 Maximal workload (watt) at Day 5 (day 4-6)
ΔCO/PCWP (peak) 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 peak exercise
ΔCO (peak) Day 0 to Day 5 (4-6) Change in maximal CO from Day 0 (infusion of study medication) to Day 5 (day 4-6) at peak exercise
ΔPCWP (rest) Day 0 to Day 5 (4-6) Change in resting PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
ΔCO (rest) Day 0 to Day 5 (4-6) Change in resting CO from Day 0 (infusion of study medication) to Day 5 (day 4-6)
ΔCVP (rest) Day 0 to Day 5 (4-6) Change in resting CVP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
ΔmPA (rest) Day 0 to Day 5 (4-6) Change in resting mPA from Day 0 (infusion of study medication) to Day 5 (day 4-6)
ΔSvO2 (rest) Day 0 to Day 5 (4-6) Change in resting SvO2 from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Δ6MWT day 3 Day 0 to Day 3 Change in 6MWT from Day 0 (infusion of study medication) to Day 3
Δ6MWT day 5 (4-6) Day 0 to Day 5 (day 4-6) Change in 6MWT from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Δ6MWT day 14 Day 0 to Day 14 Change in 6MWT from Day 0 (infusion of study medication) to Day 14
ΔNT-proBNP day 3 Day 0 to Day 3 Change in NT-proBNP from Day 0 (infusion of study medication) to Day 3
ΔNT-proBNP day 5 Day 0 to Day 5 (day 4-6) Change in NT-proBNP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
ΔNT-proBNP day 14 Day 0 to Day 14 Change in NT-proBNP from Day 0 (infusion of study medication) to Day 14
ΔPCWP (peak) Day 0 to Day 5 (4-6) Change in PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at the maximal load obtained during both invasive measurements
CO maximal Day 5 Maximal CO at Day 5 (day 4-6)
PCWP maximal Day 5 Maximal PCWP at Day 5 (day 4-6)
QOL day 3 Day 3 Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 3 after infusion of study medication
QOL day 5 Day 5 Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 5 (4-6) after infusion of study medication
QOL Day 14 Day 14 Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 14 after infusion of study medication
Trial Locations
- Locations (3)
Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet
🇩🇰Copenhagen, Denmark
Department of Cardiology, Odense University Hospital, Odense, Denmark
🇩🇰Odense, Denmark
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
🇩🇰Herlev, Denmark