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

NCT03576677 | Unknown Phase 4 DMC

• 1 other identifier: RH-HJE-LN-02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

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.

Conditions

Heart Failure

Keywords

Advanced chronic heart failure; Exercise capacity; Exercise hemodynamics; Levosimendan

Outcome Measures

Primary Outcomes (1)

• ΔCO/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 Outcomes (21)

• ΔCO/PCWP (peak)

  Day 0 to Day 5 (4-6)

• ΔCO (peak)

  Day 0 to Day 5 (4-6)

• ΔPCWP (peak)

  Day 0 to Day 5 (4-6)

• CO maximal

  Day 5

• PCWP maximal

  Day 5

Study Arms (2)

Levosimendan

ACTIVE COMPARATOR

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

Drug: Levosimendan

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Levosimendan 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.

Also known as: Simdax

Levosimendan

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Finn Gustafsson: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (3)

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

Copenhagen, DK-2100, Denmark

RECRUITING

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

Herlev, DK-2730, Denmark

RECRUITING

Department of Cardiology, Odense University Hospital, Odense, Denmark

Odense, DK-5000, Denmark

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

Simendan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Finn Gustafsson, MD, professor, PhD, DMSci

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Finn Gustafsson, MD, professor, PhD, DMSci

CONTACT

+45 35459743; finng@dadlnet.dk

Mikael K Poulsen, MD PhD

CONTACT

+45 24798402; mikael.kjaer.poulsen1@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, DMSci, Professor of Cardiology

Model Details: This is a prospective multi-center, double-blinded, placebo controlled, randomized study in patients with advanced chronic heart failure. Patients who meet the eligibility criteria will be randomized in a 1:1 ratio for treatment with 6 hours infusion of either (i) levosimendan 0.2 µg/kg/min or (ii) placebo (sterile 5% dextrose). At baseline an upright ergometer maximal exercise test is performed to determine max workload and pVO2 (Test 0). Based on this test 50% of pVO2 with corresponding workload (watt) is calculated (submax). At Day 0 patients will perform a supine ergometer maximal exercise test (Test 1) with simultaneous invasive hemodynamic measurement by Swan-Ganz catheter. Subsequently, patients will receive 6 hours infusion of study medication. At Day 5 (4-6 days after infusion of study medication) patients will repeat the supine ergometer maximal exercise test (Test 2) with simultaneous invasive hemodynamic measurements.

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: July 3, 2018
• Study Start: August 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: July 30, 2020
• Last Updated: July 17, 2019

Record last verified: 2019-07

Locations

DK (3)