Clinical trial NCT01721434: Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients
Official title: Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Muscle Weakness Conditions
Weaning Failure
Keywords: levosimendan
diaphragm function
mechanically ventilated patients
neuro-mechanical efficiency
Lead sponsor: University Medical Center Nijmegen
Sponsor class: OTHER
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2012-11-04
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Neuro-mechanical efficiency of the diaphragm
timeFrame: Artefact-free periode in the last 10 minutes of each CPAP trial
Secondary outcomes:
measure: Neuro-ventilatory efficiency of the diaphragm
timeFrame: Artefact-free periode in the last 10 minutes of each CPAP trial
measure: Oxygen consumption (VO2)
timeFrame: Artefact-free periode in the last 10 minutes of each CPAP trial
measure: Partial pressure of oxygen in arterial blood (PaO2)
timeFrame: Last minute of the 30 minute CPAP trial
measure: Accessory respiratory muscle activity
timeFrame: Measured during a one hour protocol after the second CPAP trial.
measure: Carbon dioxide production (VCO2)
timeFrame: Artefact-free periode in the last 10 minutes of each CPAP trial
measure: Partial pressure of carbon dioxide in arterial blood (PaCO2)
timeFrame: Last minute of the 30 minute CPAP trial
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Leo Heunks, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: