Effect of Levosimendan or Placebo on Exercise in Advanced Chronic Heart Failure

Heart Failure Clinical Trial

— LOCO-CHF  

Official title:

Effect of Levosimendan or Placebo on Exercise Capacity and Hemodynamics in Patients With Advanced Chronic Heart Failure (LOCO-CHF Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03576677
• Other study ID #: RH-HJE-LN-02
• Status: Recruiting
• Phase: Phase 4
• Start date: August 1, 2019
• Est. completion date: July 30, 2020

Study information

• Verified date: July 2019
• Source: Rigshospitalet, Denmark
• Contact: Finn Gustafsson, MD, professor, PhD, DMSci
• Phone: +45 35459743
• Email: finng[@]dadlnet.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: July 30, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Levosimendan
Levosimendan, 2.5 mg/mL concentrate for dilution. 5 mL of the study drug will be injected into a 245 mL isotonic glucose solution. Patients will receive a 6 hours infusion of this study drug at an infusion rate of 0.2 µg/kg/min.
• Placebo
The placebo solution will be prepared by adding 10 mL of 5% dextrose to a vial containing Soluvit (vitamin B) under aseptical conditions. 5 mL of this solution is then added to 245 mL of isotonic sodium chloride solution. 5% dextrose and vitamin B are added to ensure yellow coloring indistinguishable from the active drug (levosimendan). Patients will receive a 6 hours infusion of this study drug. Infusion rate will be calculated in similar fashion to the levosimendan group.

Locations

Country	Name	City	State
Denmark	Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark	Herlev
Denmark	Department of Cardiology, Odense University Hospital, Odense, Denmark	Odense

Sponsors (2)

Lead Sponsor	Collaborator
Finn Gustafsson	Orion Corporation, Orion Pharma

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	?CO/PCWP (submax)	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	Day 0 to Day 5 (4-6)
Secondary	?CO/PCWP (peak)	Change in CO/PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at peak exercise	Day 0 to Day 5 (4-6)
Secondary	?CO (peak)	Change in maximal CO from Day 0 (infusion of study medication) to Day 5 (day 4-6) at peak exercise	Day 0 to Day 5 (4-6)
Secondary	?PCWP (peak)	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	Day 0 to Day 5 (4-6)
Secondary	CO maximal	Maximal CO at Day 5 (day 4-6)	Day 5
Secondary	PCWP maximal	Maximal PCWP at Day 5 (day 4-6)	Day 5
Secondary	SvO2 maximal	Maximal SvO2 at Day 5 (day 4-6)	Day 5
Secondary	Workload maximal	Maximal workload (watt) at Day 5 (day 4-6)	Day 5
Secondary	?PCWP (rest)	Change in resting PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (4-6)
Secondary	?CO (rest)	Change in resting CO from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (4-6)
Secondary	?CVP (rest)	Change in resting CVP from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (4-6)
Secondary	?mPA (rest)	Change in resting mPA from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (4-6)
Secondary	?SvO2 (rest)	Change in resting SvO2 from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (4-6)
Secondary	?6MWT day 3	Change in 6MWT from Day 0 (infusion of study medication) to Day 3	Day 0 to Day 3
Secondary	?6MWT day 5 (4-6)	Change in 6MWT from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (day 4-6)
Secondary	?6MWT day 14	Change in 6MWT from Day 0 (infusion of study medication) to Day 14	Day 0 to Day 14
Secondary	?NT-proBNP day 3	Change in NT-proBNP from Day 0 (infusion of study medication) to Day 3	Day 0 to Day 3
Secondary	?NT-proBNP day 5	Change in NT-proBNP from Day 0 (infusion of study medication) to Day 5 (day 4-6)	Day 0 to Day 5 (day 4-6)
Secondary	?NT-proBNP day 14	Change in NT-proBNP from Day 0 (infusion of study medication) to Day 14	Day 0 to Day 14
Secondary	QOL day 3	Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 3 after infusion of study medication	Day 3
Secondary	QOL day 5	Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 5 (4-6) after infusion of study medication	Day 5
Secondary	QOL Day 14	Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 14 after infusion of study medication	Day 14