Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Weaning Failure Clinical Trial

Official title:

Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01721434
• Other study ID #: Levo2
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 21, 2012
• Last updated: June 9, 2015
• Start date: September 2012
• Est. completion date: May 2016

Study information

• Verified date: June 2015
• Source: University Medical Center Nijmegen
• Contact: Leo MA Heunks, MD, PhD
• Phone: 024-3617273
• Email: l.heunks[@]ic.umcn.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Muscle Weakness
• Muscle Weakness Conditions
• Paresis
• Weaning Failure

Intervention

Drug:
• Levosimendan

• Placebo
Similar coloured placebo

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Nijmegen	Orion Corporation, Orion Pharma

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuro-mechanical efficiency of the diaphragm	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.	Artefact-free periode in the last 10 minutes of each CPAP trial	No
Secondary	Neuro-ventilatory efficiency of the diaphragm	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.	Artefact-free periode in the last 10 minutes of each CPAP trial	No
Secondary	Oxygen consumption (VO2)	A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.	Artefact-free periode in the last 10 minutes of each CPAP trial	No
Secondary	Partial pressure of oxygen in arterial blood (PaO2)	A secondary outcome measure is the PaO2 at the end of a continuous positive airway pressure (CPAP) trial.	Last minute of the 30 minute CPAP trial	No
Secondary	Accessory respiratory muscle activity	To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.	Measured during a one hour protocol after the second CPAP trial.	No
Secondary	Carbon dioxide production (VCO2)	A secondary outcome measure is the carbon dioxide production during a continuous positive airway pressure (CPAP) trial.	Artefact-free periode in the last 10 minutes of each CPAP trial	No
Secondary	Partial pressure of carbon dioxide in arterial blood (PaCO2)	A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.	Last minute of the 30 minute CPAP trial	No