Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by University Medical Center Nijmegen
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Leo Heunks, University Medical Center Nijmegen
ClinicalTrials.gov Identifier:
NCT01721434
First received: September 21, 2012
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

Levosimendan is a relatively new drug that improves cardiac contractility in patients with heart failure. Its main mechanism of action is enhanced binding of calcium to the myocardial contractile proteins. Recent data from our lab showed that levosimendan improves contractility of human diaphragm in vitro (muscle fibers from COPD patient diaphragm) and in vivo (healthy subjects). Accordingly, levosimendan may appear of value in the treatment of disorders associated with impaired respiratory muscle function, such as mechanically ventilated patients.We hypothesize that levosimendan could improve respiratory muscle function in mechanically ventilated patients commencing a CPAP trial.


Condition Intervention Phase
Muscle Weakness Conditions
Weaning Failure
Drug: Levosimendan
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Further study details as provided by University Medical Center Nijmegen:

Primary Outcome Measures:
  • Neuro-mechanical efficiency of the diaphragm [ Time Frame: Artefact-free periode in the last 10 minutes of each CPAP trial ] [ Designated as safety issue: No ]
    The primary outcome measure is the neuro-mechanical efficiency(i.e. the ratio of diaphragm electrical activity and transdiaphragmatic pressure) of the diaphragm during a continuous positive airway pressure (CPAP) trial.


Secondary Outcome Measures:
  • Neuro-ventilatory efficiency of the diaphragm [ Time Frame: Artefact-free periode in the last 10 minutes of each CPAP trial ] [ Designated as safety issue: No ]
    A secondary outcome measure is the neuro-ventilatory efficiency (i.e. the ratio of diaphragm electrical activity and tidal volume) during a continuous positive airway pressure (CPAP) trial.

  • Oxygen consumption (VO2) [ Time Frame: Artefact-free periode in the last 10 minutes of each CPAP trial ] [ Designated as safety issue: No ]
    A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.

  • Partial pressure of oxygen in arterial blood (PaO2) [ Time Frame: Last minute of the 30 minute CPAP trial ] [ Designated as safety issue: No ]
    A secondary outcome measure is the PaO2 at the end of a continuous positive airway pressure (CPAP) trial.

  • Accessory respiratory muscle activity [ Time Frame: Measured during a one hour protocol after the second CPAP trial. ] [ Designated as safety issue: No ]
    To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.

  • Carbon dioxide production (VCO2) [ Time Frame: Artefact-free periode in the last 10 minutes of each CPAP trial ] [ Designated as safety issue: No ]
    A secondary outcome measure is the carbon dioxide production during a continuous positive airway pressure (CPAP) trial.

  • Partial pressure of carbon dioxide in arterial blood (PaCO2) [ Time Frame: Last minute of the 30 minute CPAP trial ] [ Designated as safety issue: No ]
    A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.


Estimated Enrollment: 42
Study Start Date: September 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Levosimendan
Levosimendan 0.2 ug/kg/min intravenous for a single 7 hours.
Drug: Levosimendan
Other Name: Simdax
Placebo Comparator: Placebo
Similar coloured placebo intravenous for a single 7 hours
Drug: Placebo
Similar coloured placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • mechanical ventilation > 3 days
  • informed consent
  • able to sustain a CPAP trial for 30 minutes
  • PaO2/FiO2 ratio > 200 mmHg
  • ventilatory settings: positive end expiratory pressure <= 10 cmH2O, pressure support <= 10 cmH2O

Exclusion Criteria:

  • pre-existent muscle disease (congenital or acquired) or diseases/disorders known to be associated with myopathy including auto-immune diseases
  • pre-existent cardiac disease (based on history, electrocardiography and transthoracic echocardiography)
  • upper airway/esophageal pathology (i.e. recent surgery, esophageal varices, diaphragmatic hernia)
  • phrenic nerve lesions
  • pregnancy, breast feeding
  • severe renal failure (serum creatinine > 150 umol/L)
  • severe hepatic failure
  • recent (within 5 days) nasal bleeding
  • systolic blood pressure < 120 mmHg
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721434

Contacts
Contact: Leo MA Heunks, MD, PhD 024-3617273 l.heunks@ic.umcn.nl
Contact: Jonne Doorduin, MSc 024-3617273 j.doorduin@ic.umcn.nl

Locations
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Gelderland, Netherlands, 6500HB
Contact: Leo MA Heunks, MD, PhD    024-3617273    l.heunks@ic.umcn.nl   
Contact: Jonne Doorduin, MSc    024-3617273    j.doorduin@ic.umcn.nl   
Sponsors and Collaborators
University Medical Center Nijmegen
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Leo Heunks, MD, PhD Radboud University
  More Information

No publications provided

Responsible Party: Leo Heunks, MD, PhD, University Medical Center Nijmegen
ClinicalTrials.gov Identifier: NCT01721434     History of Changes
Other Study ID Numbers: Levo2
Study First Received: September 21, 2012
Last Updated: November 1, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Center Nijmegen:
levosimendan
diaphragm function
mechanically ventilated patients
neuro-mechanical efficiency

Additional relevant MeSH terms:
Muscle Weakness
Paresis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Simendan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014