Effect of Levosimendan or Placebo on Exercise in Advanced Chronic Heart Failure (LOCO-CHF)

Finn Gustafsson

Status and phase: Unknown; Phase 4

Conditions: Heart Failure

Treatments: Drug: Placebo; Drug: Levosimendan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03576677

RH-HJE-LN-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups, including a placebo group

Levosimendan

Active Comparator group

Description:

Study participants in this arm will receive a 6 hours infusion of levosimendan 0.2 µg/kg/min.

Treatment:

Drug: Levosimendan

Placebo

Placebo Comparator group

Description:

Study participants in this arm will receive a 6 hours infusion of placebo (sterile isotonic sodium chloride + 5% dextrose + vitamin B)

Treatment:

Drug: Placebo