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Trial registered on ANZCTR


Registration number
ACTRN12613001114730
Ethics application status
Approved
Date submitted
29/09/2013
Date registered
4/10/2013
Date last updated
1/03/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Noninvasive ventilation in weaning patients with hypoxemic acute respiratory failure (h-ARF): a multicentre randomized controlled study.
Scientific title
A study on the effects of noninvasive ventilation used as weaning strategy on duration of invasive mechanical ventilation when compared to a conventional weaning approach with endotracheal tube in place in patients with hypoxemic acute respiratory failure.
Secondary ID [1] 283249 0
The pilot study for this trial was registered on the ANZCTR: ACTRN12609000606280
Universal Trial Number (UTN)
Trial acronym
Weaning with NIV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Weaning in Hypoxemic Acute Respiratory Failure 290121 0
Condition category
Condition code
Respiratory 290505 290505 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Non invasive ventilation (NIV) will be applied through a helmet, which is a transparent latex-free polyvinylchloride hood, or by mask. The ventilator will be set with the same positive end expiratory pressure (PEEP) and inspiratory support applied to the patient before extubation. During the first 24 hours, NIV will be maintained continuously. Thereafter brief discontinuation (less than 5min) will be tolerated for nursing the patients (face, oral hygiene) or to change the non invasive interface. To enhance patient tolerance to NIV, a mild sedation with low doses of remifentanyl (0.025-0.15 microg/kg/min) and/or clonidine (bolus 1 microg/kg/min, than 0.003-0.01 microg/kg/min, max 750-900 microg/die) and/or propofol (10-50 mg/hr) will be allowed. Alternation of interfaces (helmet and mask) will also be accepted during the study period to increase patient tolerance. PEEP will be reduced by 2 cmH2O per hour whenever the PaO2/FiO2 ratio will exceed 225, to a minimum level of 8 cmH2O. No decrease in PEEP will be undertaken if PaO2/FiO2 ratio is below 225. In this case, the attendant physician will re-evaluate the patient after 6 hours. Inspiratory support will be reduced by 2 cmH2O per hour to maintain PaCO2 <= 50 mmHg and pH >= 7.35, to a minimum level of 10 cmH2O. When NIV is set at the minimum levels of PEEP and inspiratory support (8 cmH2O and 10 cmH2O, respectively) and the PaO2/FiO2 is higher than 250, a 30-minute spontaneous breathing trial (SBT) with a Venturi mask 35% will be attempted. The SBT will be interrupted and NIV resumed in case of severe dyspnea, activation of accessory muscles, and paradoxical abdominal motion, respiratory rate (RR) > 30 breaths/min, SpO2 < 90%. At the end of the trial an arterial blood gas analysis will be performed: the patients will be considered successfully weaned off NIV if pH >= 7.35, PaCO2 <= 50 mmHg and PaO2 >= 70 mmHg.
The total duration of NIV treatment will depend on how quick, according to the established algorithm, will be the weaning process and it can vary on a case by case basis.
Intervention code [1] 287978 0
Treatment: Devices
Comparator / control treatment
The control group is composed by patients invasively ventilated that will be weaned off the ventilator decreasing the PEEP and pressure support but with the endotracheal tube in place. In the control group, PEEP will be reduced by 2 cmH2O per hour whenever the PaO2/FiO2 ratio will exceed 225, to a minimum level of 8 cmH2O. No decrease in PEEP will be undertaken if PaO2/FiO2 ratio is below 225. In this case, the attendant physician will re-evaluate the patient after 6 hours. Inspiratory support will be reduced by 2 cmH2O per hour to maintain PaCO2 <= 50 mmHg and pH >= 7.35, to a minimum level of 10 cmH2O. When pressure support ventilation (PSV) is set at the minimum levels of PEEP and inspiratory support (8 cmH2O and 10 cmH2O, respectively) and the PaO2/FiO2 is higher than 250, a 30-minute SBT will be attempted. In the control group, the SBT consists in making patient breathing through the circuit of a flow triggered ventilator, set to deliver 5 cmH2O of PEEP and 5 cmH2O of inspiratory support at 35% oxygen. The SBT will be interrupted and increased the total support in case of severe dyspnea, activation of accessory muscles, and paradoxical abdominal motion, RR > 30 breaths/min, SpO2 < 90%. At the end of the trial an arterial blood gas analysis will be performed: the patients will be extubated if pH >= 7.35, PaCO2 <= 50 mmHg and PaO2 >= 70 mmHg.
The total duration of invasive mechanical ventilation treatment will depend on how quick, according to the established algorithm, will be the weaning process and it can vary on a case by case basis.
Control group
Active

Outcomes
Primary outcome [1] 290526 0
Aim of the study is to investigate whether in patients with hypoxemic ARF early extubation followed by immediate application of NIV (interventional group) reduces the overall number of days spent in ICU.
Timepoint [1] 290526 0
Clinicians will monitor daily the number of days spent in intensive care unit (ICU).
Secondary outcome [1] 304728 0
Duration (days) of continuous intravenous sedation (monitored by clinicians).
Timepoint [1] 304728 0
Daily monitored during intensive care unit (ICU) stay after the inclusion in the weaning protocol.
Secondary outcome [2] 304729 0
Side effects / complications of invasive mechanical ventilation: infection, sepsis and ventilator associated pneumonia (VAP), monitored by clinicians.
Timepoint [2] 304729 0
Daily monitored during ICU stay after the inclusion in the weaning protocol.
Secondary outcome [3] 304730 0
ICU mortality, monitored by clinicians.
Timepoint [3] 304730 0
Daily monitored during ICU stay after the inclusion in the weaning protocol.
Secondary outcome [4] 304731 0
Number of tracheotomy, monitored by clinicians.
Timepoint [4] 304731 0
Daily monitored during ICU stay after the inclusion in the weaning protocol.
Secondary outcome [5] 304732 0
Hospital mortality, monitored by clinicians.
Timepoint [5] 304732 0
Daily monitored after discharge from the ICU.

Eligibility
Key inclusion criteria
Invasive mechanical ventilation duration > 48 hours; PaO2/FiO2 ranging between 200 and 300 with a positive end-expiratory pressure PEEP > 8 and < = 12 cmH2O and a FiO2 <= 0.6; Pressure Support Ventilation (PSV) with a total applied pressure (i.e. PEEP + inspiratory support) <= 25 cmH2O; PaCO2 <= 50 mmHg; pH >= 7.35; Respiratory rate (RR) <= 30/min; Core body temperature <= 38.5 (degrees celsius); Glasgow Coma Scale (GCS) >= 10; Presence of clearly audible cough during suctioning; Tracheal suctioning<= 2/hr
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe hemodynamic instability as assessed: a) systolic arterial pressure < 90 mmHg, despite adequate filling, b) need for continuous infusion of epinephrine, norepinephrine or vasopressine, c) need for dopamine or dobutamine > 5microg/Kg/min
Life-threatening arrhythmias or ECG signs of ischemia; Severe sepsis or septic shock;
ARF secondary to congestive heart failure, neurological disorders, status asmaticus, chronic obstructive pulmonary disease; Tracheotomy; Copious secretions or uncontrolled vomiting; Spinal cord injury or neuro-muscular disorder; Presence of 2 or more criteria of organ failure; Body mass index >= 30; Obstructive sleep apnea syndrome

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)
Every centre have envelops containing the group of the assignment of the patients.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Online generator of one sequence for each center of 20 cases each, equally distributed between the 2 groups.
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
According to data from the previous study by Vaschetto et al. (Intensive Care Medicine (2012) 38:1599–1606), the sample size has been so calculated:
1) H0: mean ICU length of stay in the intervention group equal to the control group = 21;
2) H1: mean ICU length of stay of intervention group = 15 vs. mean ICU length of stay of control group = 21;
3) Standard Deviation of ICU length of stay in intervention (11) and control group (13);
4) Study design: multicenter RCT;
5) Significance: 5%;
6) Power: 80%;
7) type of comparison: 2 tails;
8) Statistic Test: t-test with Satterthwaite correction.

According to these hypothesis, 65 patients for each group are needed.

The two groups will be compared by using the Mann–Whitney test. Frequency distributions will be compared by using chi-square test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/10/2013
Actual
13/10/2013
Date of last participant enrolment
Anticipated
31/05/2016
Actual
19/10/2016
Date of last data collection
Anticipated
Actual
30/11/2016
Sample size
Target
130
Accrual to date
Final
130
Recruitment outside Australia
Country [1] 5421 0
Italy
State/province [1] 5421 0
Country [2] 5422 0
China
State/province [2] 5422 0

Funding & Sponsors
Funding source category [1] 287988 0
University
Name [1] 287988 0
Eastern Piedmont University "A. Avogadro"
Country [1] 287988 0
Italy
Primary sponsor type
Individual
Name
Navalesi Paolo
Address
University od Eastern Piedmont
Department of "Medicina Traslazionale" and Department of Anesthesia and Intensive Care
Corso Mazzini 18, 28100 Novara
Country
Italy
Secondary sponsor category [1] 286707 0
None
Name [1] 286707 0
Address [1] 286707 0
Country [1] 286707 0
Other collaborator category [1] 277622 0
Individual
Name [1] 277622 0
Hai Bo Qiu
Address [1] 277622 0
Department of Critical Care Medicine,
Southeast University, Zhongda Hospital,
NO. 87 Dingjiaqiao, Nan Jing, China
Country [1] 277622 0
China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289916 0
Comitato Etico Interaziendale A.O.U. “Maggiore della Carita”, ASL BI, ASL NO, ASL VC, ASL VCO
Ethics committee address [1] 289916 0
Ethics committee country [1] 289916 0
Italy
Date submitted for ethics approval [1] 289916 0
15/04/2013
Approval date [1] 289916 0
21/06/2013
Ethics approval number [1] 289916 0
CE 88/13

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

Contacts
Principal investigator
Name 43070 0
Prof Paolo Navalesi
Address 43070 0
University od Eastern Piedmont
Department of "Medicina Traslazionale" and Department of Anesthesia and Intensive Care,
Corso Mazzini 18, 28100 Novara
Country 43070 0
Italy
Phone 43070 0
+ 39 0321 3733406
Fax 43070 0
+ 39 0321 3733406
Email 43070 0
paolo.navalesi@med.uniupo.it
Contact person for public queries
Name 43071 0
Paolo Navalesi
Address 43071 0
University od Eastern Piedmont
Department of "Medicina Traslazionale" and Department of Anesthesia and Intensive Care, Corso Mazzini 18, 28100 Novara
Country 43071 0
Italy
Phone 43071 0
+ 39 0321 3733406
Fax 43071 0
+ 39 0321 3733406
Email 43071 0
paolo.navalesi@med.uniupo.it
Contact person for scientific queries
Name 43072 0
Paolo Navalesi
Address 43072 0
University od Eastern Piedmont
Department of "Medicina Traslazionale" and Department of Anesthesia and Intensive Care, Corso Mazzini 18, 28100 Novara
Country 43072 0
Italy
Phone 43072 0
+ 39 0321 3733406
Fax 43072 0
+ 39 0321 3733406
Email 43072 0
paolo.navalesi@med.uniupo.it

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
EmbaseEarly extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.2019https://dx.doi.org/10.1007/s00134-018-5478-0
N.B. These documents automatically identified may not have been verified by the study sponsor.