Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000815864
Ethics application status
Approved
Date submitted
27/07/2012
Date registered
3/08/2012
Date last updated
3/08/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Can Neurally Adjusted Ventilatory Assist improve the outcome of mechanical ventilation compared to Pressure Support Ventilation? A multicenter randomized clinical trial.
Scientific title
Effects of two different ventilatory modes i.e., neurally adjusted ventilatory assist and pressure support ventilation on duration of mechanical ventilation and intensive care unit lenght of stay in patients with acute respiratory failure. A multicenter randomized clinical trial.
Secondary ID [1] 280909 0
Nil
Universal Trial Number (UTN)
Trial acronym
NAVA_MRCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duration of mechanical ventilation during acute respiratory failure 286987 0
Lenght of stay in intensive care unit in patient with acute respiratory failure 286990 0
Condition category
Condition code
Respiratory 287321 287321 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Neurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation controlled by diaphragmatic electrical signals. Brefly the application of NAVA requires the introduction of a catheter to measure the electrical activity of the diaphragm (EAdi). NAVA relies, opposite to conventional assisted ventilation modes, on the EAdi to trigger the ventilator breath and to adjust the ventilatory assist to the neural drive. The amplitude of the ventilator assist is determined by the instantaneous EAdi and the NAVA level set by the clinician. The NAVA level amplifies the Eadi signal and determines instantaneous ventilator assist on a breath-to-breath basis.
In patients enrolled in the NAVA group, EAdi catheter will be positioned and NAVA ventilation will be kept continuously (24 hours per day) till extubation (on rough average 7 days expected).
If no EAdi signal will be detected patients will be maintained in assist control mode until the signal will be detectable. If the signal will remain undetectable, the patient will anyway be included in the NAVA group (intention-to-treat analysis).
The ventilator will be initially set according to the following criteria: Positive End-Expiratory Pressure (PEEP) as set by the attending physician; NAVA level between 1 and 3 cmH2O/microV (to maintain Tidal Volume (VT) between 5-8 ml/kg and mean peak EAdi between 7 and 15 microV); EAdi trigger 0.5 microV and flow trigger 5, assuring that the vast majority of the breaths are neurally triggered; peak Pressure airway (Paw) alarm set to 45 cm H2O.
After enrollment, patients will be tested every day for readiness to wean according to following criteria: suctioning less than twice per hour; clearly audible cough during suctioning; Glasgow Coma Scale (GCS) equal or greater than 8; heart rate equal or less than 120 beats per minute (bpm) and systolic blood pressure (SBP) equal or greater than 90 mmHg and equal or less than 180 mmHg; dopamine or dobutamine equal or less than 5 mcg/kg/min or norepinephrine equal or less than 0.1 mcg/kg/min; PaO2/FiO2 equal or greater than 150 mmHg; PEEP equal or less than 8 cmH2O; VT equal or greater than 5ml/kg; respiratory rate (RR) < 40/min; absence of evident respiratory distress (diaphoresis, accessory muscle recruitment, thoraco-abdominal paradox); pH equal or greater than 7.35; Richmond Agitation Sedation Scale (RASS) between -1 and + 1.
If the patient will meet all the criteria, a spontaneous breathing trial (SBT) in Continuous Positive Airway Pressure (CPAP) 2 cmH2O will be performed for 30 minutes.
At the end of SBT arterial blood gases (ABG) will be sampled and the patient will be considered ready for extubation if all the follow criteria will be excluded: agitation and anxiety and/or depressed mental status (RASS = +3 or = -4); increased accessory muscle activity and or dyspnoea (VAS equal or greater than 7); RR/VT equal or greater than 105 b*min-1*L-1; PaO2 equal or less than 60 mmHg on FiO2 > 50%; pH < 7.32; SBP < 90 mmHg; cardiac arrhythmias not previously present.
If SBT will be stopped for failure the same mode will be started again with settings able to restore clinical stability.
If the patient will be able to maintain spontaneous breathing for the 48 hours following extubation, he/she will be considered as extubation success and the protocol will be ended. Otherwise, the subject will be re-intubated and data collection and observation will be continued.
Criteria for re-intubation are: emergency, such as respiratory or cardiac arrest and gasping for air; neurologic deterioration; need for continuous infusion of epinephrine, norepinephrine, vasopressine, or dopamine or dobutamine > 5 mcg/Kg/min to maintain SBP equal or greater than 90 mmHg despite adequate filling; upper airway obstruction with stridor and/or tirage; unmanageable tracheo-bronchial secretions; respiratory distress (SpO2 <90%; RR > 35 bpm; visible accessory muscle recruitment or thoracic-abdominal paradox, despite administration of oxygen).
After extubation, it will be also possible to ventilate not-invasively (NIV) the patient, either for preventing (i.e. NIV started immediately after extubation in at risk patients) or treating post-extubation respiratory failure (i.e. NIV started at established respiratory failure). When feasible, NIV will be applied in NAVA mode for patients included in the NAVA group. Tracheotomy will be performed between 7 and 14 days of invasive mechanical ventilation without likelihood of prompt extubation.
Intervention code [1] 285343 0
Treatment: Other
Comparator / control treatment
In patients enrolled in the Pressure Support Ventilation (PSV) group, Electrical Activity of the diaphragm (EAdi) catheter will not be positioned. PSV will be kept continuously (24 hours per day) till extubation (on rough average 8 days expected).
The ventilator will be initially set according to the following criteria: Positive End-Expiratory Pressure (PEEP) as set by the attending physician; Pressure Support (PS) level set by the attending physician to maintain Tidal Volume (VT) between 5-8 ml/kg; Flow inspiratory trigger equal to 5, cycling off equal to 30% of inspiratory flow peak.
After enrollment, patients will be tested every day for readiness to wean according to same criteria of interventional group.
If the patient will meet all the criteria, a spontaneous breathing trial (SBT) in Continuous Positive Airway Pressure (CPAP) 2 cmH2O will be performed for 30 minutes.
At the end of SBT arterial blood gases (ABG) will be sampled and the patient will be considered ready for extubation if all the same interventional group criteria will be excluded.
If SBT will be stopped, or SBT failure criteria will be met, the same mode will be started again with settings able to restore clinical stability.
If the patient will be able to maintain spontaneous breathing for the 48 hours following extubation, he/she will be considered as extubation success and the protocol will be ended. Otherwise, the subject will be re-intubated and data collection and observation will be continued. After extubation, it will be also possible to ventilate not-invasively (NIV) the patient, either for preventing (i.e. NIV started immediately after extubation in at risk patients) or treating post-extubation respiratory failure (i.e. NIV started at established respiratory failure).
Control group
Active

Outcomes
Primary outcome [1] 287597 0
Duration of mechanical ventilation (expressed in days).
In both groups the days of invasive mechanical ventilation will be counted from the first day of intubation to the successful extubation. With successful extubation we intend an extubation followed by a 48 hours period of spontaneous breathing.
These data can be assessed by looking at the bedside chart data.
Timepoint [1] 287597 0
The total lenght of invasive mechanical ventilation from intubation to the successful extubation will be assesed is at the end of the trial.
Primary outcome [2] 287598 0
Intensive care unit lenght of stay (expressed in days).
In both groups the lenght of stay in the Intensive care unit will be calculated as the number of days from the entrance to the discharge of the patients.
These data can be assessed by looking at the medical records database available the recruiting hospitals.
Timepoint [2] 287598 0
The Intensive care unit lenght of stay will be counted as the total days from the the Intensive care unit entrance to the intensive care unit discharge and will be assessed at the end of the trial.
Secondary outcome [1] 298499 0
Weaning time.
In both groups the weaning time will be calculated as the number of days spent both on NAVA and on PSV.
These data can be assessed by looking at the medical records database available in the recruiting hospitals.
Timepoint [1] 298499 0
The weaning time will be calculated from the first day of readiness to wean to extubation and will be assessed at the end of the trial.
Secondary outcome [2] 298500 0
Rate of re-intubation.
In both groups the rate of re-intubation will be assessed as the number of patients intubated within 48 hours after extubation divided by the total number of patients included in that group.
These data can be assessed by looking at the medical records database available in the recruiting hospitals.
Timepoint [2] 298500 0
First 48 hours after extubation.
Secondary outcome [3] 298501 0
Number of tracheotomies.
In both groups we will count the number of tracheotomies performed.
These data can be assessed by looking at the medical records database available in the recruiting hospitals.
Timepoint [3] 298501 0
The numbre of tracheotomies will be counted untill the discharge from the intensive care unit, at the end of the trial.
Secondary outcome [4] 298502 0
Hospital charges per patient during Intensive care unit stay.
In both groups the cost per patient will be calculated in euro as the average charge for one day of intensive care unit stay of each centres.
These data can be assessed by looking at the medical records database available in the recruiting hospitals.
Timepoint [4] 298502 0
The cost will include total gross hospital charges per
patient stay per day and will be assessed at the end of the trial.
Secondary outcome [5] 298503 0
Hospital length of stay.
In both group the lenght of stay in the hospital will be calculated as the number of days from the entrance to the discharge of the patient from the hospital. These data can be assessed by looking at the medical records database available in the recruiting hospitals.
Timepoint [5] 298503 0
The hospital lenght of stay will be counted as total days from the hospital entrance to the discharge of the patient and will be assessed at the end of the trial.

Eligibility
Key inclusion criteria
Intubated patients
Previous mechanical ventilation >= 24 hours
Ability to effectively trigger the ventilator
Expected ventilatory assistance >= 48 hours
No scheduled surgery
No inclusion in other research protocol
No neuromuscular or neurologic disease
Absence of contraindications to feeding tube positioning (including esophageal surgery in the previous 12 months and/or history of esophageal varices)
PaO2/FiO2 >150 with PEEP >= 5 cmH2O
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Lack of informed consent or refusal
Organ failure >= 3
Poor short term prognosis or decision to limit life support

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The patients will be screened for inclusion in the study by the physician in charge who is blind on the allocation till the moment of the inclusion. Once included the patient in the study, the physician in charge will allocate the patient according to the central randomization system by computer accessible through a dedicated website. Randomization will be performed by means of computerized binary random sequence. To balance the case-control series a block randomization will be applied.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be performed by means of computerized binary random sequence. To balance the case-control series a block randomization will be applied.
Patients will be automatically allocated to one of the two groups by a software accessible through a dedicated website.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment outside Australia
Country [1] 4423 0
Italy
State/province [1] 4423 0

Funding & Sponsors
Funding source category [1] 285701 0
University
Name [1] 285701 0
Dipartimento di Medicina Traslazionale, Universita del Piemonte Orientale Amedeo Avogadro, Alessandria-Novara-Vercelli, Italy.
Country [1] 285701 0
Italy
Primary sponsor type
University
Name
Dipartimento di Medicina Traslazionale, Universita del Piemonte Orientale Amedeo Avogadro, Alessandria-Novara-Vercelli, Italy.
Address
Via Solaroli 17, 28100 Novara, Italy.
Country
Italy
Secondary sponsor category [1] 284529 0
None
Name [1] 284529 0
Address [1] 284529 0
Country [1] 284529 0
Other collaborator category [1] 276978 0
Commercial sector/Industry
Name [1] 276978 0
Maquet Critical Care
Address [1] 276978 0
Rontgenvagen 2, SE-171 95 Solna, Sweden
Country [1] 276978 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287699 0
Comitato Etico Interaziendale AOU "Maggiore della Carita" di Novara, ASL BI, ASL NO, ASL VC, ASL VCO
Ethics committee address [1] 287699 0
Ethics committee country [1] 287699 0
Italy
Date submitted for ethics approval [1] 287699 0
Approval date [1] 287699 0
20/07/2012
Ethics approval number [1] 287699 0
CE 104/12

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34483 0
Address 34483 0
Country 34483 0
Phone 34483 0
Fax 34483 0
Email 34483 0
Contact person for public queries
Name 17730 0
Paolo Navalesi
Address 17730 0
Via Solaroli 17, 28100 Novara.
Country 17730 0
Italy
Phone 17730 0
+39 0321 3733406
Fax 17730 0
+39 0321 3733406
Email 17730 0
[email protected]
Contact person for scientific queries
Name 8658 0
Paolo Navalesi
Address 8658 0
Via Solaroli 17, 28100 Novara.
Country 8658 0
Italy
Phone 8658 0
+39 0321 3733406
Fax 8658 0
+39 0321 3733406
Email 8658 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAutomated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children.2014https://dx.doi.org/10.1002/14651858.CD009235.pub3
N.B. These documents automatically identified may not have been verified by the study sponsor.