Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000665932
Ethics application status
Approved
Date submitted
17/01/2011
Date registered
30/06/2011
Date last updated
28/11/2018
Date data sharing statement initially provided
28/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot feasibility study of Permissive Hypercapnia, Alveolar Recruitment, Low Airway Pressure (PHARLAP) in patients with ARDS
Scientific title
A pilot study of Permissive Hypercapnia, Alveolar Recruitment, Low Airway Pressure (PHARLAP) in ventilated patients with ARDS to study adherence to study protocol
Secondary ID [1] 253422 0
nil
Universal Trial Number (UTN)
U1111-1119-0698
Trial acronym
PHARLAP feasibility pilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute respiratory distress syndrome 260968 0
Condition category
Condition code
Respiratory 259105 259105 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The PHARLAP strategy incorporates a step-wise recruitment manoeuvre to PEEP 40cmH2O in pressure control ventilation, decremental PEEP titration and tolerance of hypercapnia. The staircase recruitment manoeuvre and PEEP titration are performed once per day for 5 days with small re-recruits throughout the day if the patient is disconnected or desaturates. The combination of these individual therapies represents a treatment approach considered by some to be the best available care. In fact these therapies have been shown to improve blood oxygenation, reduce lung injury and attenuate cytokine response. The PHARLAP strategy has been compared to the current best practice in a pilot randomized, controlled study (ACTRN12607000465459). As compare to the current best practice, the PHARLAP strategy allowed an oxygenation and compliance improvement and an attenuation of some inflammatory cytokines over a 7 day period. The PHARLAP strategy includes pressure control ventilation (PCV, 15 cm H2O above PEEP) with patients in supine, 30 degrees head up. The fraction of inspired oxygen (FIO2) is reduced until oxygen saturation was 90-92%. For the SRM, the PEEP is increased in a stepwise manner to 20, then 30 and then 40 cm H2O every two minutes, and then reduced to 25, then 22.5, then 20, then 17.5 or then 15 cm H2O every three minutes until a decrease in SaO2 of 1% from maximum SaO2 is observed. This is defined as the derecruitment point. PEEP is then increased to 40 cm H2O for one minute and returned to a PEEP level 2.5 cm H2O above the de-recruitment point (defined as optimal PEEP). Following this SRM step the tidal volume is decreased to achieve a plateau pressure less than 30 cm H2O. Hypercapnia is tolerated and acidosis will only be treated if the pH is less than 7.15 by increasing respiratory rate to a maximum of 38 breaths per minute, or administration of sodium bicarbonate. The participants will receive one SRM daily (with decremental PEEP titration). In addition, PEEP will be transiently elevated to 40 cm H2O (with PCV at 15 cm H2O) for one minute if oxygen desaturation less than 90% occurred or after disconnection from the ventilator. Patients are assessed daily for weaning. Weaning will be commenced when all of the following occurred: respiratory rate < 35 breaths per minute, PaO2 > 60 mm Hg, SpO2 > 90% with fraction of inspired oxygen < 0.4 and PEEP < 10 cm H2O, mean arterial pressure > 60 mm Hg without inotrope infusions or sedatives.
Intervention code [1] 257868 0
Not applicable
Comparator / control treatment
There is no control. We are studying adherence to the PHARLAP protocol.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 261959 0
Adherence to protocol for staircase recruitment (SRM) and PEEP titration - the ventilator pressure and volume are recorded by an independent research nurse directly from the mechanical ventilator and the maximum pressure reached during the SRM and any reasons for termination of the SRM.
Timepoint [1] 261959 0
Daily for 5 days
Secondary outcome [1] 268877 0
Adherence to tidal volume and pressure limitation - read directly from the mechanical ventilator
Timepoint [1] 268877 0
Daily for 5 days

Eligibility
Key inclusion criteria
1. the diagnosis of ARDS within the last 48 hours
2. age > 15 years
3. the presence of both an intra-arterial line and central venous catheter
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. chest trauma
2. an intercostal catheter with air leak,
3. a pneumothorax on chest x-ray,
4. bronchospasm on auscultation,
5. raised intracranial pressure,
6. mean arterial pressure less than 60mmHg or arrhythmias.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The adherence to protocol study has ben completed and we are now conducting a multicentre randomised controlled trial of PHARLAP.
Date of first participant enrolment
Anticipated
20/02/2011
Actual
6/06/2011
Date of last participant enrolment
Anticipated
Actual
11/07/2011
Date of last data collection
Anticipated
Actual
16/07/2011
Sample size
Target
10
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 12569 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 12570 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 3535 0
5042

Funding & Sponsors
Funding source category [1] 258334 0
University
Name [1] 258334 0
Monash University
Country [1] 258334 0
Australia
Primary sponsor type
University
Name
Monash University
Address
99 Commercial Rd, Melbourne, VIC, 8004
Country
Australia
Secondary sponsor category [1] 257490 0
Hospital
Name [1] 257490 0
The ALfred
Address [1] 257490 0
Commercial Rd Prahran, VIC, 3181
Country [1] 257490 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260311 0
Flinders Hospital HREC
Ethics committee address [1] 260311 0
Flinders Dve
Bedford Park, SA, 5042
Ethics committee country [1] 260311 0
Australia
Date submitted for ethics approval [1] 260311 0
Approval date [1] 260311 0
25/02/2011
Ethics approval number [1] 260311 0
Ethics committee name [2] 260312 0
Prince Charles HREC
Ethics committee address [2] 260312 0
Rode Road
Chermside QLD 4032
Ethics committee country [2] 260312 0
Australia
Date submitted for ethics approval [2] 260312 0
01/02/2011
Approval date [2] 260312 0
Ethics approval number [2] 260312 0

Summary
Brief summary
Objectives: To determine if the study protocol (PHARLAP – permissive hypercapnia, alveolar recruitment and low airway pressure) can be implemented safely and effectively at a centre where there is no previous experience with the trial in order to determine the feasibility of establishing this as a large multi-centre trial in Australia and New Zealand.

We hypothesis that PHARLAP strategy can be safely implemented in any ICU in Australia and New Zealand.


Proposed Methods:
Study design: (control groups should receive best treatment currently available).

There is no control group. The treatment group receives the PHARLAP treatment protocol and data is collected to determine the adherence to study protocol.

The PHARLAP strategy includes pressure control ventilation (PCV, 15 cm H2O above PEEP) with patients in supine, 30 degrees head up. The fraction of inspired oxygen (FIO2) is reduced until oxygen saturation was 90-92%. For the SRM, the PEEP is increased in a stepwise manner to 20, then 30 and then 40 cm H2O every two minutes, and then reduced to 25, then 22.5, then 20, then 17.5 or then 15 cm H2O every three minutes until a decrease in SaO2 of 1% from maximum SaO2 is observed. This is defined as the derecruitment point. PEEP is then increased to 40 cm H2O for one minute and returned to a PEEP level 2.5 cm H2O above the de-recruitment point (defined as optimal PEEP). Following this SRM step the tidal volume is decreased to achieve a plateau pressure less than 30 cm H2O. Hypercapnia is tolerated and acidosis will only be treated if the pH is less than 7.15 by increasing respiratory rate to a maximum of 38 breaths per minute, or administration of sodium bicarbonate. The participants will receive one SRM daily (with decremental PEEP titration). In addition, PEEP will be transiently elevated to 40 cm H2O (with PCV at 15 cm H2O) for one minute if oxygen desaturation less than 90% occurred or after disconnection from the ventilator. The SRMs will be repeated once per day until the patient is ready for weaning.
Patients are assessed daily for weaning. Weaning will be commenced when all of the following occurred: respiratory rate < 35 breaths per minute, PaO2 > 60 mm Hg, SpO2 > 90% with fraction of inspired oxygen < 0.4 and PEEP < 10 cm H2O, mean arterial pressure > 60 mm Hg without inotrope infusions or sedatives.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 32097 0
A/Prof Carol Hodgson
Address 32097 0
ANZIC-RC DEPM Monash University
Level 6, 99 Commercial Road
Melbourne Vic 3004
Country 32097 0
Australia
Phone 32097 0
61 3 99030598
Fax 32097 0
Email 32097 0
[email protected]
Contact person for public queries
Name 15344 0
A/Prof Carol Hodgson
Address 15344 0
ANZIC Research Centre
School of Public Health & Preventive Medicine Monash University, The Alfred Centre
99 Commercial Road, Melbourne VIC 3004
Country 15344 0
Australia
Phone 15344 0
61 3 9903 0379
Fax 15344 0
Email 15344 0
[email protected]
Contact person for scientific queries
Name 6272 0
A/Prof Carol Hodgson
Address 6272 0
ANZIC Research Centre
School of Public Health & Preventive Medicine Monash University, The Alfred Centre
99 Commercial Road, Melbourne VIC 3004
Country 6272 0
Australia
Phone 6272 0
61 3 9903 0379
Fax 6272 0
Email 6272 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.