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

NCT ID: NCT03576677

Last Updated: 2019-07-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2020-07-30

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levosimendan

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

Group Type: ACTIVE_COMPARATOR

Levosimendan

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Simdax

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

Finn Gustafsson

OTHER

Sponsor Role: lead

Responsible Party

Finn Gustafsson

MD, PhD, DMSci, Professor of Cardiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Finn Gustafsson, MD, professor, PhD, DMSci

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Locations

Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status: RECRUITING

Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark

Herlev, , Denmark

Site Status: RECRUITING

Department of Cardiology, Odense University Hospital, Odense, Denmark

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Finn Gustafsson, MD, professor, PhD, DMSci

Role: CONTACT

finng@dadlnet.dk

+45 35459743

Mikael K Poulsen, MD PhD

Role: CONTACT

mikael.kjaer.poulsen1@rsyd.dk

+45 24798402

Facility Contacts

Finn Gustafsson, MD, professor, PhD, DMSci

Role: primary

finng@dadlnet.dk

+45 35459743

Lærke Nelson, MD

Role: backup

laerke.marie.nelson@regionh.dk

+45 35459549

Morten Schou, MD, PhD

Role: primary

schou@dadlnet.dk

+45 40523920

Jacob E Møller, MD, professor, PhD, DMSci

Role: primary

jem@dadlnet.do

+45 51439630

Mikael K Poulsen, MD, PhD

Role: backup

mikael.kjaer.poulsen1@rsyd.dk

+45 24798402

Other Identifiers

RH-HJE-LN-02

Identifier Type: -

Identifier Source: org_study_id