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Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

Primary Purpose

Muscle Weakness Conditions, Weaning Failure

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Levosimendan
Placebo
Sponsored by
University Medical Center Nijmegen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscle Weakness Conditions focused on measuring levosimendan, diaphragm function, mechanically ventilated patients, neuro-mechanical efficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Radboud University Nijmegen Medical CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Levosimendan

Placebo

Arm Description

Levosimendan 0.2 ug/kg/min intravenous for a single 7 hours.

Similar coloured placebo intravenous for a single 7 hours

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Oxygen consumption (VO2)
A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.
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.
Accessory respiratory muscle activity
To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.
Carbon dioxide production (VCO2)
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)
A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.

Full Information

First Posted
September 21, 2012
Last Updated
June 9, 2015
Sponsor
University Medical Center Nijmegen
Collaborators
Orion Corporation, Orion Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT01721434
Brief Title
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

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
May 2016 (Anticipated)
Study Completion Date
May 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Nijmegen
Collaborators
Orion Corporation, Orion Pharma

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Weakness Conditions, Weaning Failure
Keywords
levosimendan, diaphragm function, mechanically ventilated patients, neuro-mechanical efficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Levosimendan
Arm Type
Experimental
Arm Description
Levosimendan 0.2 ug/kg/min intravenous for a single 7 hours.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Similar coloured placebo intravenous for a single 7 hours
Intervention Type
Drug
Intervention Name(s)
Levosimendan
Other Intervention Name(s)
Simdax
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Similar coloured placebo
Primary Outcome Measure Information:
Title
Neuro-mechanical efficiency of the diaphragm
Description
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.
Time Frame
Artefact-free periode in the last 10 minutes of each CPAP trial
Secondary Outcome Measure Information:
Title
Neuro-ventilatory efficiency of the diaphragm
Description
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.
Time Frame
Artefact-free periode in the last 10 minutes of each CPAP trial
Title
Oxygen consumption (VO2)
Description
A secondary outcome measure is the oxygen consumption during a continuous positive airway pressure (CPAP) trial.
Time Frame
Artefact-free periode in the last 10 minutes of each CPAP trial
Title
Partial pressure of oxygen in arterial blood (PaO2)
Description
A secondary outcome measure is the PaO2 at the end of a continuous positive airway pressure (CPAP) trial.
Time Frame
Last minute of the 30 minute CPAP trial
Title
Accessory respiratory muscle activity
Description
To determine the effects of levosimendan on accessory respiratory muscle function, ventilator settings are adapted after the last CPAP-trial.
Time Frame
Measured during a one hour protocol after the second CPAP trial.
Title
Carbon dioxide production (VCO2)
Description
A secondary outcome measure is the carbon dioxide production during a continuous positive airway pressure (CPAP) trial.
Time Frame
Artefact-free periode in the last 10 minutes of each CPAP trial
Title
Partial pressure of carbon dioxide in arterial blood (PaCO2)
Description
A secondary outcome measure is the PaCO2 at the and of a continuous positive airway pressure (CPAP) trial.
Time Frame
Last minute of the 30 minute CPAP trial

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leo MA Heunks, MD, PhD
Phone
024-3617273
Email
l.heunks@ic.umcn.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Jonne Doorduin, MSc
Phone
024-3617273
Email
j.doorduin@ic.umcn.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leo Heunks, MD, PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500HB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leo MA Heunks, MD, PhD
Phone
024-3617273
Email
l.heunks@ic.umcn.nl
First Name & Middle Initial & Last Name & Degree
Jonne Doorduin, MSc
Phone
024-3617273
Email
j.doorduin@ic.umcn.nl

12. IPD Sharing Statement

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Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients

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