ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12613001006730

Ethics application status

Approved

Date submitted

9/09/2013

Date registered

10/09/2013

Date last updated

13/07/2017

Type of registration

Retrospectively registered

Titles & IDs

Public title

Optimising positive end expiratory pressure (PEEP) in mechanically ventilated patients with acute respiratory distress syndrome (ARDS)

Scientific title

The investigation of model based methods to provide an optimal level of positive end expiratory pressure (PEEP) to mechanically ventilated patients with acute respiratory distress syndrome (ARDS)

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U111111429939

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute Respiratory Distress Syndrome (ARDS)

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The planned interventions will test the response of patient lung when it is ventilated at different positive end expiratory pressure (PEEP) to determine the best PEEP settings specific to each patient at a particular time.

The best PEEP is found to occur during minimal elastance. Minimal elastance PEEP is able to maximise lung recruitment and avoid overdistension. It is important ventilation is optimised as soon as possible when the patient is admitted to the ICU. Delayed proxy consent will be sought for these reasons.

The intervention tests a mathematical model (Time-varying elastance model) to better inform intensive care clinicians about the lung condition, and select a PEEP at minimal elastance during a PEEP titration protocol. Patients whose PEEP selected by the mathematical model, implemented by the clinician, will be compared with the outcomes of patients who have had their PEEP determined solely by clinical judgement.

Details of PEEP titration protocol
1. A staircase recruitment manoeuvre (RM) is performed (C.L. Hodgson et al., 2011). During RM, PEEP is increased in steps of 5cmH2O from a base level of 5cmH2O PEEP.
2. PEEP is increased until peak airway pressure (PIP) reaches a limit of 55cmH2O (or lower, if clinician feels this is too high for the patient)
3. Each PEEP is maintained for 10-15 breathing cycles before a subsequent increase.
4. Elastance is calculated at each PEEP
5. The minimum elastance PEEP is determined
6. This PEEP is recommended to the attending clinician
7. If the clinician feels this PEEP is appropriate, they will re-perform steps 1 and 2. The purpose of this increase is to re-recruit the lung after decremented portion of RM. On the decremented portion of the RM, the clinician will end the PEEP decrease on the recommended PEEP.
8. Otherwise the clinician will set the PEEP to a PEEP they feel is more appropriate. If the clinician chooses to ignore the model suggestion, this will be recorded. Further the data from the patient will still be recorded.

Every 3 hours or when the patient is turned in the bed the following adjustments are to be made:

1. PEEP is increased in 3 steps of 2cmH2O with 10~15 breathing cycles at each step.
2. If the Elastance shows an increase at each and every step, then revert back to the original PEEP setting minus 1cmH2O.
3. If the Elastance shows a decrease at each and every step, then set to the final PEEP setting (a total of 6cmH2O increase in PEEP).
4. If the Elastance decreases at the first step and then increases at any subsequent step, then set to the PEEP that yielded the minimum Elastance value during the adjustment procedure.
5. If the Elastance increases at the first step and then decreases at any subsequent step, then leave PEEP at original setting. This instance is cause for the clinician to consider a full recruitment manoeuvre.

The study will run for at least 48 hours, and until there has been significant resolution of their lung condition. Following each intervention, clinical staff in the ICU will be given the option of following the recommended settings as determined by the mathematical model.

Data regarding clinician compliance with the protocol, the number of low oxygen recordings (using standard pulse oximetry monitoring), length of mechanical ventilation and ICU stay, total oxygen “dose” and ICU mortality will be collected and compared with a matched cohort.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

The comparator cohort for this study includes patients that are not enrolled for the actual trial. Their treatment will not be in any way affected of altered as a result of this trial. They will receive normal care from ICU professionals as per usual hospital routine. These data were obtained in previous observational trial (Feb 2010 to Dec 2011) ACTRN12611001179921.

Control group

Historical

Outcomes

Primary outcome [1]

Number of desaturation events (measured by continuous pulse oximetry, where SpO2 is less than 88%)

Timepoint [1]

The occurance of desaturation events of a patient is recorded throughout the trial or for at least 48 hours.

Primary outcome [2]

Length of mechanical ventilation

Timepoint [2]

The length of MV is recorded as the duration from start of the trial until the discontinuation of mechanical ventilation.

Secondary outcome [1]

PEEP selection based on minimal elastance has been suggested in some clinical and experimental trials [1-3]. However, there is yet confirmation of the PEEP selected at this elastance is optimal. The primary outcome the study will further verify and validate the benefit of minimal elastance selected PEEP during mechanical ventilation.

1. Carvalho, A., et al. (2007). "Positive end-expiratory pressure at minimal respiratory elastance represents the best compromise between mechanical stress and lung aeration in oleic acid induced lung injury." Critical Care 11(4): R86.
2. Lambermont, B., et al. (2008). "Comparison of functional residual capacity and static compliance of the respiratory system during a positive end-expiratory pressure (PEEP) ramp procedure in an experimental model of acute respiratory distress syndrome." Critical Care 12(4): R91.
3. Chiew, Y. S., et al. (2011). "Model-based PEEP Optimisation in Mechanical Ventilation." BioMedical Engineering OnLine 10(1): 111.

Timepoint [1]

The assessment is conducted after completion of the clinical trials.

Secondary outcome [2]

The study also aims to give clinicians the confidence to allow clinical staff to adjust PEEP levels, which may enable the clinicians more time to look at other aspects of the patient’s health and improve the standard of care in the intensive care unit.

This assessment will be conducted by using qualitative questionaires and feedback of clinical staffs that were involde during the trial

Timepoint [2]

The assessment is conducted after completion of the clinical trials.

Eligibility

Key inclusion criteria

1. Patient on mechanical ventilation.
2. Patients diagnosed with all degrees of ARDS (PF ratio <300) as per the Berlin Definition (2012) (The ARDS Definition Task Force, A. 2012), by intensive care clinicians.
3. Arterial line in situ.

Minimum age

16 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Patients who are likely to be discontinued from MV within 24 hours.
2. Patients aged less than 16.
4. Patients who are moribund and/or not expected to survive for more than 72 hours.
5. Patients whose care could be compromised if given increased sedation and/or muscle relaxants for the purpose of assessing lung recruitment.
6. Lack of clinical equipoise by ICU medical staff managing the patient.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Mechanically ventilated patients are unable to communicate due to their requirements for analgesia (opioids, such as morphine) and sedation (hypnotic drugs, such as diazepam or “valium”). They also frequently have metabolic or septic encephalopathies, or brain injury. Thus, virtually no patient will ever be competent to provide informed consent or desire to participate. Patients on MV who meet the inclusion criteria will be enrolled in the trial, once proper consents are obtained form family or whanau.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

No randomising will occur in this trial.

Masking / blinding

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Not Applicable

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities
Other reasons/comments

Other reasons

The trial has collected sufficient data for analysis and testing. The clinical protocol requires additional changes.

Date of first participant enrolment

Anticipated

6/09/2013

Actual

9/09/2013

Date of last participant enrolment

Anticipated

Actual

19/11/2014

Date of last data collection

Anticipated

Actual

19/11/2014

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Canterbury

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

Government body

Name

Canterbury District Health Board

Address

Level 2
H Block
The Princess Margaret Hospital
Cashmere Road
Cashmere
PO Box 1600
Christchurch 8140

Country

New Zealand

Secondary sponsor category [1]

University

Name [1]

University of Canterbury

Address [1]

Private Bag 4800
Christchurch 8140

Country [1]

New Zealand

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Comittee (Southern)

Ethics committee address [1]

Health and Disability Ethics Committees
1 the Terrace
PO Box 5013
Wellington
6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

10/05/2013

Approval date [1]

08/06/2013

Ethics approval number [1]

13/STH/84

Summary

Brief summary

Intensive care clinicians use Mechanical Ventilation on a daily basis in the ICU to treat patients with injured lungs. An important setting on the ventilator machines is known as positive end expiratory pressure or PEEP. This controls the pressure in the lung at the end of the breath, and its accuracy is critical in the successful treatment of injured lungs. 

Currently, doctors have no standard way of selecting the PEEP for each patient, and use their clinical intuition, or their “gut-feeling”. Different patients have different lungs and as such, selecting PEEP this way might lead to an incorrect PEEP setting for that patient. This might cause the patient to require longer stays in the ICU and/or or further lung injury. 

This study aims to evaluate a computer based method of PEEP selection and is based on prior research conducted here in the Christchurch ICU. Because this method of PEEP selection is specific to each patient, it is anticipated ventilation better matched to their lungs. This could lead to healthier lungs and as a result, require the patient to spend less time in the ICU.

Trial website

Trial related presentations / publications

1..	Kannangara DO, Newberry F, Howe S, Major V, Redmond D, Szlavecz A, Chiew YS, Pretty C, Benyo B, Shaw GM, Chase JG, Estimating the True Respiratory Mechanics during Asynchronous Pressure Controlled Ventilation, Biomedical Signal Processing and Control, 30: 70-78, 2016.
2.	Damanhuri NS, Chiew YS, Othman NA, Docherty PD, Pretty C, Shaw, GM, Desaive T, Chase JG, “Assessing Respiratory Mechanics Using Pressure Reconstruction Method in Mechanically Ventilated Spontaneous Breathing Patient,” Computer Methods and Programs in Biomedicine, 2016, Vol 130, pp. 175-185
4..	Major V, Corbett S, Redmond R, Beatson A, Glassenbury D, Chiew YS, Pretty C, Desaive T, Szlavecz A, Benyo B, Shaw GM, and Chase JG, Respiratory mechanics assessment for reverse-triggered breathing cycles using pressure reconstruction. Biomedical Signal Processing and Control 2016, 23:1-9.
5.	Szlavecz A, Chiew YS, Redmond D, A Beatson A, Glassenbury D, Corbett S, Major V, Pretty C, Shaw GM, Benyo B, Desaive T, Chase JG, The Clinical Utilisation of Respiratory Elastance Software (CURE Soft): a bedside software for real-time respiratory mechanics monitoring and mechanical ventilation management. BioMedical Engineering OnLine 2014, 13:140.

Public notes

Contacts

Principal investigator

Name

Dr Geoffery Shaw

Address

Department of Intensive Care
Christchurch Hospital
Private Bag 4710
Christchurch 8140

Country

New Zealand

Phone

+643364 1077

Fax

geoff.shaw@cdhb.health.nz

Contact person for public queries

Name

Geoffery Shaw

Address

Department of Intensive Care
Christchurch Hospital
Private Bag 4710
Christchurch 8140

Country

New Zealand

Phone

+643364 1077

Fax

geoff.shaw@cdhb.health.nz

Contact person for scientific queries

Name

J Geoffrey Chase

Address

University of Canterbury Department of Mechanical Engineering Private Bag 4800 Christchurch 8140

Country

New Zealand

Phone

+6421342743

Fax

geoff.chase@canterbury.ac.nz

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

Source	Title	Year of Publication	DOI
Embase	Respiratory mechanics assessment for reverse-triggered breathing cycles using pressure reconstruction.	2016	https://dx.doi.org/10.1016/j.bspc.2015.07.007
Dimensions AI	Negative Lung Elastance in Mechanically Ventilated Spontaneously Breathing Patient	2017	https://doi.org/10.1016/j.ifacol.2017.08.2269
Embase	A virtual patient model for mechanical ventilation.	2018	https://dx.doi.org/10.1016/j.cmpb.2018.08.004
Dimensions AI	Basis function identification of lung mechanics in mechanical ventilation for predicting outcomes of therapy changes: A first virtual patient	2018	https://doi.org/10.1016/j.ifacol.2018.09.151
Dimensions AI	Validation of a Model-based Method for Estimating Functional Volume Gains during Recruitment Manoeuvres in Mechanical Ventilation	2018	https://doi.org/10.1016/j.ifacol.2018.11.637
Embase	Predictive Virtual Patient Modelling of Mechanical Ventilation: Impact of Recruitment Function.	2019	https://dx.doi.org/10.1007/s10439-019-02253-w
Dimensions AI	Model-based PEEP titration versus standard practice in mechanical ventilation: a randomised controlled trial	2020	https://doi.org/10.1186/s13063-019-4035-7

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically