Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000115437
Ethics application status
Approved
Date submitted
2/02/2007
Date registered
8/02/2007
Date last updated
8/02/2007
Type of registration
Retrospectively registered

Titles & IDs
Public title
Rate of Reintubation in Mechanically Ventilated Neurosurgical and Neurologic Patients: Evaluation of a Systematic Approach to Weaning and Extubation. A Randomized Controlled Trial
Scientific title
Rate of Reintubation in Mechanically Ventilated Neurosurgical and Neurologic Patients: Evaluation of a Systematic Approach to Weaning and Extubation. A Randomized Controlled Trial
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mechanically Ventilated Neurosurgical and Neurologic Patients 1607 0
Condition category
Condition code
Neurological 1711 1711 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who did not meet exclusion criteria were randomized, as soon as all inclusion criteria were satisfied, to intervention or control group.
Patient randomized to the intervention group were weaned and extubated following a protocol based on:
a) A daily screening of physiological and clinical variables to assess readiness for the Spontaneous Breathing Trial. The criteria for readiness, which had been concurred by all the physicians in staff and agreed by nurses and respiratory therapists, were: 1) Glasgow Coma Scale not lower than 8, 2) presence of clearly audible cough during suctioning 15, 3) tracheal suctioning not exceeding 2/hour, 4) normal Sodium (Na+) blood values, 5) core temperature < 38.5° (C) during the previous 8 hours, 6) inspired oxygen fraction not exceeding (FiO2) 0.4, 7) pH not lower than 7.35, and arterial carbon dioxide tension pressure (PaCO2) not exceeding 50 mm Hg, 8) PaO2/FiO2 above 200 with Positive end-expiratory pressure not exceeding 5 cmH2O, 9) heart rate not exceeding 125 beat / min, 10) systolic blood pressure higher than 90 mmHg without epinephrine or norepinephrine infusion and with dopamine infusion not exceeding 5 mgr/Kg/min.
The above described screening was performed every morning until all criteria were all met.
b) The patients who passed the screening underwent a one-hour Spontaneous Breathing Trial, breathing through the circuit of a flow triggered ventilator, set to deliver 2-3 cmH2O of continuous positive airway pressure, with FiO2 0.4. The trial was interrupted and mechanical ventilation resumed whenever one of the following occurred: 1) respiratory rate > 35/min, 2) evident respiratory distress (diaphoresis, accessory muscle recruitment, thoraco-abdominal paradox), 3) SpO2 < 90%, 4) systolic arterial pressure < 90 mmHg or > 180 mmHg, 5) heart rate > 140 /min, 6) altered sensorium (obnubilation or agitation). At the end of the trial, patients who had a Respiratory rate/Tidal Volume ratio of 105 or less were considered to succeed the trial and underwent arterial blood gas analysis; patients who had PaO2/FiO2 above 200, pH not lower than 7.35, and PaCO2 not exceeding 50 mmHg were immediately extubated. Conversely, if the Respiratory rate/Tidal Volume ratio exceeded 105 or the arterial blood gas analysis criteria were not met, mechanical ventilation was resumed.

The same physiologic and clinical data were available for both groups, however, they were systematically organized and checked (protocol) only for the intervention group.
A priori power analysis showed that a recruitment of 300 patients (150 patients per group) over a 21-month period would have allowed detecting a decrease in reintubation from 15% to 5%, with 80% power at the 5% two-sided level of significance. We planned 2 interim analysis after 7 and 14 months, performed by an investigator not involved in the clinical management of patients. The study began on October 1st 2002 and ended on June 30th 2004. Patients already enrolled at June 30th 2004 completed the trial irrespective of the group of randomization.
Intervention code [1] 1583 0
Other interventions
Comparator / control treatment
Patients included in the control group were weaned and extubated based on the sole physician clinical judgment (usual care). Patients who were not reintubated within 48 hours were considered successfull extubated
Control group
Active

Outcomes
Primary outcome [1] 2382 0
Rate of reintubation secondary to extubation failure. Patients who were not reintubated within 48 hours were considered successfully extubated. All patients were therefore continuously monitored during the 48 hours and were reintubated as soon as they met the predefined criteria for reintubation:1) emergency, such as respiratory or cardiac arrest, and gasping for air, 2) neurological deterioration (coma or agitation requiring continuous sedative intravenousinfusion), 3) hemodynamic instability (i.e. need for continuous catecholamine infusion despite adequate filling or life threatening arrhythmia), 4) upper airway obstruction with stridor and tirage, 5) unmanageable excess of tracheo-bronchial secretions, 6) respiratory distress, as assessed by the combination of SpO2 < 90%, tachypnea (> 35/min), and visible accessory muscle recruitment or thoraco-abdominal paradox, despite maximal oxygen administration and non-invasive ventilation.
Timepoint [1] 2382 0
Continuously monitored for 48 hours after first attempt of extubation
Secondary outcome [1] 4137 0
Mortality in Intensive Care Unit, rate of tracheotomy in Intensive Care Unit, duration of mechanical ventilation, and length of stay in Intensive Care Unit.
Timepoint [1] 4137 0
Patients were screened every day for death and tracheotomy. Days spent on mechanical ventilation and length of stay in ICU were determined for all patients when the ICU file was closed (death or ICU discharge). The perception of the protocol by the Intensive Care Unit staff was assessed by means of a Likert-like scale after completion of the study and before analyzing data.

Eligibility
Key inclusion criteria
Considered eligible when 1) had received mechanical ventilation for more than 12 hours, 2) had no need for continuous i.v. sedative infusion and/or controlled mechanical ventilation, 3) were able to trigger the ventilator.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) patients admitted already intubated from other institution, 2)presence of tracheotomy, 3) lesion affecting the upper airway, 4) pre-existing decision to withdraw or limit life support, 5)no scheduled surgery in the following 72 hours.

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)
Contacting the holder of the allocation schedule who was off-site
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Participants were blinded
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2002
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment outside Australia
Country [1] 478 0
Italy
State/province [1] 478 0

Funding & Sponsors
Funding source category [1] 1861 0
Hospital
Name [1] 1861 0
Hospital Azienda Ospedaliera Ospedale Niguarda-Ca’ Granda
Country [1] 1861 0
Italy
Primary sponsor type
Hospital
Name
Azienda Ospedaliera Ospedale Niguarda-Ca’ Granda, Milan, Italy
Address
Country
Italy
Secondary sponsor category [1] 1671 0
Hospital
Name [1] 1671 0
Fondazione S. Maugeri
Address [1] 1671 0
IRCCS
Pavia
Italy
Country [1] 1671 0
Italy

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3471 0
Azienda Ospedaliera Ospedale Niguarda-Ca’ Granda
Ethics committee address [1] 3471 0
Milan
Ethics committee country [1] 3471 0
Italy
Date submitted for ethics approval [1] 3471 0
Approval date [1] 3471 0
Ethics approval number [1] 3471 0

Summary
Brief summary
The study has been designed to assess whether a systematic approach to weaning and extubation based on daily screening of meaningful physiological and clinical variables, including indexes of neurologic function, followed by a trial of spontaneous breathing, is superior to the sole physician’s judgment in preventing the rate of reintubation secondary to extubation failure in patients with neurologic disorders.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27517 0
Address 27517 0
Country 27517 0
Phone 27517 0
Fax 27517 0
Email 27517 0
Contact person for public queries
Name 10772 0
Paolo Navalesi
Address 10772 0
Intensive Care Unit. SCDU Anestesia, Terapia Intensiva e Rianimazione Generale. Aziensa ospedaliera "Maggiore della Carità". Corso Mazzini 18.
28100 Novara
Novara
Country 10772 0
Italy
Phone 10772 0
+39 0321 3733406
Fax 10772 0
+39 0321 3733406
Email 10772 0
[email protected]
Contact person for scientific queries
Name 1700 0
Paolo Navalesi
Address 1700 0
Intensive Care Unit. SCDU Anestesia, Terapia Intensiva e Rianimazione Generale. Aziensa ospedaliera "Maggiore della Carità". Corso Mazzini 18.
28100 Novara
Country 1700 0
Italy
Phone 1700 0
+39 0321 3733406
Fax 1700 0
+39 0321 3733406
Email 1700 0
[email protected]

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