Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000790640
Ethics application status
Approved
Date submitted
19/07/2014
Date registered
24/07/2014
Date last updated
13/08/2019
Date data sharing statement initially provided
5/04/2019
Date results information initially provided
5/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Prospective Randomised Trial of Two Tidal Volume Ventilator Strategies in Patients Undergoing Major Surgery
Scientific title
A prospective randomised trial of intraoperative tidal volume ventilation with 6ml/kg (Ideal Body weight) and positive end expiratory pressure (PEEP) of 5 cm H2O versus 10ml/kg (Ideal Body weight) and PEEP of 5 cm H2O, in adult patients undergoing major surgery.
Secondary ID [1] 285016 0
None
Universal Trial Number (UTN)
U1111-1159-4667
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Effects of ventilation in patients undergoing major surgery 292530 0
Condition category
Condition code
Anaesthesiology 292834 292834 0 0
Anaesthetics
Surgery 292835 292835 0 0
Other surgery
Respiratory 292836 292836 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In patients undergoing major surgery who mechanical ventilation patients with an endotracheal tube, the ventilation strategy will be randomised to compare either a 6ml/kg or 10ml/kg tidal volume strategy in combination with PEEP.
Intervention code [1] 289850 0
Treatment: Devices
Comparator / control treatment
Both group will receive the intervention; the ventilation strategy will either a 6ml/kg or 10ml/kg tidal volume in combination with PEEP.
Control group
Dose comparison

Outcomes
Primary outcome [1] 292701 0
The number of patients with a postoperative pulmonary complication. Pulmonary complications include pneumonia, bronchospasm, atelectasis, pulmonary congestion, pulmonary embolism, respiratory failure and requirements for mechanical ventilation, pleural effusion and pneumothorax.
Updated from
The number of patients with a postoperative pulmonary complication. Pulmonary complications include pneumonia, bronchospasm, atelectasis, pulmonary congestion, pulmonary embolism, respiratory failure and requirements for mechanical ventilation.  
Reason: This change was made after recruitment of all participants but before data analysis.The trial steering committee made recommendations that pleural effusion and pneumothorax are respiratory complications and should be included in the primary composite outcome. The trial steering committee made recommendations that pulmonary embolus should be excluded from the primary composite outcome and included as a secondary outcome. These modifications were made after technology became available which allowed the natural language processing of radiology reports.
Updated on 13/08/2019 12:02:44 PM
Timepoint [1] 292701 0
Within the first 7 days after surgery
Updated from
Duration of hospital stay  
Reason: Change to the primary outcome timepoint was advised by the trial steering committee. The modification resulted after further review of the current literature which allows the protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [1] 309520 0
Requirements for post-operative Intensive Care
Timepoint [1] 309520 0
Duration of hospital stay
Secondary outcome [2] 309521 0
Number of hours in ICU
Timepoint [2] 309521 0
Duration of ICU stay
Secondary outcome [3] 309523 0
30 day mortality
Timepoint [3] 309523 0
30 days postoperatively
Secondary outcome [4] 373811 0
Incidence of each individual component of the primary composite outcome
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were made after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.

Updated on 13/08/2019 12:02:44 PM
Timepoint [4] 373811 0
Duration of hospital stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [5] 373812 0
Incidence of postoperative respiratory complications
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [5] 373812 0
Duration of hospital stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [6] 373813 0
Incidence of pulmonary embolism
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [6] 373813 0
At 7 post operative days and during hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [7] 373814 0
Incidence of systemic inflammatory response syndrome
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after technology became available which allowed the natural language processing of radiology reports which allowed a feasible method of identification of these outcomes. The above modification also resulted after further review of the current literature which allowed our protocol to be further aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [7] 373814 0
At 7 post operative days and during hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [8] 373815 0
Incidence of sepsis
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [8] 373815 0
At 7 post operative days and during hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [9] 373816 0
Incidence of wound infection (superficial and deep)
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [9] 373816 0
At 7 post operative days and during hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [10] 373817 0
Rate of intraoperative need of vasopressor
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [10] 373817 0
At 7 post operative days and during hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [11] 373818 0
Incidence of unplanned intensive care unit (ICU) admission
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [11] 373818 0
Duration of hospital length of stay
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [12] 373819 0
Rate of need for medical emergency team call
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis. These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [12] 373819 0
Duration of hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Secondary outcome [13] 373820 0
Incidence of in-hospital mortality
Inserted
 
Reason: This change was made after recruitment of all participants but before data analysis.These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Timepoint [13] 373820 0
Duration of hospital length of stay
Inserted
 
Reason: These modifications were recommended by the trial steering committee after further review of the current literature which allowed our protocol to be aligned with previous comparable studies.
Updated on 13/08/2019 12:02:44 PM
Deleted Outcome
Length of hospital stay  
Timepoint
Duration of hospital stay
Reason: Repetition of secondary endpoint.
Updated on 13/08/2019 12:02:44 PM

Eligibility
Key inclusion criteria
Patients will be eligible to participate in this study if:
1. The patient is aged 40 years or older
2. The treating anaesthetist expects that the patient will remain intubated for a period of equal to or greater than two hours
3. The patient will have an arterial line inserted for routine monitoring of blood pressure during the surgical procedure
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be ineligible for participation if:
1. The patient is pregnant and/or lactating
2. The patient has planned thoracic surgery
3. The patient has planned cardiac surgery
4. The patient has planned intracranial neurosurgery
5. Previously enrolment in this Trial

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)
All adult patients scheduled to undergoing a major surgical procedure and require mechanical ventilation in the operating suite of the Austin Hospital will be screened for eligibility. Once informed consent has been obtained, randomisation will be by means of sealed opaque envelopes with permuted blocks of variable size. Each envelope will contain a study arm allocation with the tidal volume target as well as a copy of a simplified study protocol.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation will be used using computer generated software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
There are two study groups associated with this trial:
1. Volume control ventilation with a tidal volume 6ml/kg of Ideal Body Weight and PEEP of 5cm H2O.
2. Volume control ventilation with tidal volume 10ml/kg of Ideal Body Weight and PEEP of 5cm H2O.

Calculation of tidal volume & use of PEEP.
Tidal volume for each participant will be calculated base on a) the patient’s gender and b) the patient’s ideal body weight (IBW). IBW will be calculated by the treating anaesthetist using the following standard formula.
For males: 50 + 0.91 (centimetres in height – 152.4)
For females 45.5 + 0.91 (centimetres in height – 152.4)

Immediately after randomisation, the tidal volume will be set on the ventilator for either a target of 6ml/kg or 10 ml/kg based on ideal body weight and gender. This allocated tidal volume target will be maintained for the duration of the surgical procedure. At the end of the surgical procedure the patient will have their anaesthesia reversed and will be woken and weaned from mechanical ventilation according to standard hospital protocol. There is no change to the type of anaesthesia provide or any oxygenation or ventilation management of enrolled patients during the surgical procedures.
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a prospective randomised trial comparing two tidal volume targets in patients undergoing major surgery. Data will be analysed on an intention-to-treat basis. Comparisons will be made using t-test and ANOVA for repeated-measures or Wilcoxon rank-signed test and Kruskall-Wallis according to the underlying distribution for continuous data and Chi-square for categorical data. A Kaplan-Meier curve with log-rank test will be performed to further compare in-hospital mortality and rate of discharge home where appropriate. Logistic regression analysis will also be performed to adjust for baseline imbalances.

Recruitment
Recruitment status
Completed
Updated from
Recruiting  
Reason: Last participant recruited and study completed
Updated on 5/04/2019 12:00:05 PM
Updated from
Not yet recruiting  
Reason: Study has commenced with Full Ethics approval
Updated on 17/09/2014 11:21:37 AM
Date of first participant enrolment
Anticipated
1/08/2014
Actual
1/09/2014
Updated from
 
Reason: Minor delay in Full Ethics approval.
Updated on 17/09/2014 11:21:37 AM
Date of last participant enrolment
Anticipated
30/06/2017
Actual
21/11/2018
Updated from
31/12/2015 
Reason: Trial recruitment slower than expected.
Updated on 13/01/2016 2:21:26 PM
Updated from
 
Reason: Slow in recruitment
Updated on 5/04/2019 12:00:05 PM
Date of last data collection
Anticipated
Actual
21/12/2018
Updated from
 
Reason: Last data collected
Updated on 5/04/2019 12:00:05 PM
Sample size
Target
1240
Accrual to date
Final
1240
Updated from
900 
Reason: Based on inferences for a single proportion primarily on our own institution’s incidence of respiratory complications from the FLURO Trial of 10.8%, with a power (1-B) value of 0.80, a type I error rate (alpha) of 5%, in order to reduce the incidence of composite respiratory complications from 10.8% (p0) (known incidence of respiratory complications from our FLURO study[36]), to 7.4% (p1) (proportion of the intervention group), we will require a sample size of approximately 594 patients in each group, which will be rounded to 620 patients per group (total of 1240 patients) to adjust for a possible 3% data loss.

Updated on 24/04/2017 1:46:51 PM
Updated from
 
Reason: Recruited as per protocol
Updated on 5/04/2019 12:00:05 PM
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2753 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 8452 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 289628 0
Hospital
Name [1] 289628 0
Departments of Intensive Care and Anaesthesia, Austin Hospital
Country [1] 289628 0
Australia
Primary sponsor type
Hospital
Name
Departments of Intensive Care and Anaesthesia, Austin Hospital
Address
Studley Road, Heidelberg, Victoria, 3084, Australia
Country
Australia
Secondary sponsor category [1] 288315 0
None
Name [1] 288315 0
Address [1] 288315 0
Country [1] 288315 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291369 0
Research Ethics Unit Austin Health
Ethics committee address [1] 291369 0
Studley Road, Heidelberg, Victoria, 3084, Australia
Ethics committee country [1] 291369 0
Australia
Date submitted for ethics approval [1] 291369 0
Approval date [1] 291369 0
14/07/2014
Ethics approval number [1] 291369 0
HREC/14/Austin/260

Summary
Brief summary
There is no good evidence to guide the choice of breath size (tidal volume) delivered by the breathing machine during anaesthesia. In a recent multi-centre study, we found that anaesthetists deliver a variable tidal volumes with some patients receiving low-tidal volumes (6-7 ml/kg) and others receiving high-tidal volumes (9-10 ml/Kg) according to clinician preference. We also found that they typically positive end expiratory pressure (PEEP) (pressure to keep lung when breathing out has been completed) at an average modest value of 5.0 cmH2O. Thus, in Victoria and the Austin hospital in patients under general anaesthesia administered tidal volume can be variably high or low and PEEP is often applied at modest levels. Because of such variability and the possibility that one approach or another may be better at avoiding lung complications after anaesthesia, we wish to perform prospective randomised trial to evaluate the impact and outcome of two different tidal volume strategies during anaesthesia.

Specifically, we wish to conduct a pilot single-centre prospective randomised trial comparing a low tidal volume (6 ml/kg) to a higher tidal volume (10 ml/kg) tidal volume strategy in combination with PEEP at 5 cm H2O for patients undergoing major surgery. The anticipated sample size is 900 participants over a 18 month period. Patients will be randomly allocated to either low or control tidal volume ventilation for the period of their surgical procedure to test the hypothesis that one of these two approaches in superior at decreasing post-surgical lung complications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50066 0
Dr Laurence Weinberg
Address 50066 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 50066 0
Australia
Phone 50066 0
+61 3 94965000
Fax 50066 0
+61 3 94596421
Email 50066 0
laurence.weinberg@austin.org.au
Contact person for public queries
Name 50067 0
Dr Laurence Weinberg
Address 50067 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 50067 0
Australia
Phone 50067 0
+61 3 94965000
Fax 50067 0
+61 3 94596421
Email 50067 0
laurence.weinberg@austin.org.au
Contact person for scientific queries
Name 50068 0
Dr Laurence Weinberg
Address 50068 0
Department of Anaesthesia
Austin Hospital, Studley Road, Heidelberg, 3084, Victoria
Country 50068 0
Australia
Phone 50068 0
+61 3 94965000
Fax 50068 0
+61 3 94596421
Email 50068 0
laurence.weinberg@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Updated from
 
Reason: Participants have not consented to sharing of their data.
Updated on 13/08/2019 12:02:44 PM
No/undecided IPD sharing reason/comment
Participants have not consented to sharing of their data. Reasonable requests for the de-identified database can me made in writing to the trial Chief Investigator.
Updated from
 

Updated on 13/08/2019 12:02:44 PM


What supporting documents are/will be available?

No Supporting Documents Provided
Results publications and other study-related documents

No Study Results Provided