Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000465459
Ethics application status
Approved
Date submitted
7/09/2007
Date registered
13/09/2007
Date last updated
2/03/2020
Date data sharing statement initially provided
5/02/2020
Date results information initially provided
2/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Permissive Hypercapnia, Alveolar Recruitment and Limited Airway Pressures reduce injury in Acute Respiratory Distress Syndrome.
Scientific title
A phase II randomised controlled trial in acute respiratory distress syndrome of permissive hypercapnia, alveolar recruitment and limited airway pressures to determine effects on inflammatory cytokines.
Secondary ID [1] 467 0
N/A
Universal Trial Number (UTN)
Trial acronym
PHARLAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute respiratory distress syndrome. 2347 0
Condition category
Condition code
Respiratory 2452 2452 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Initial setup: After randomization the patient will receive a stepwise recruitment manoeuvre followed by a decrimental positive end expiratory pressure (PEEP) trial commencing at 25cmH20 to determine the optimal PEEP for that patient. Plateau airway pressures will then be reduced until either the tidal volume is < 4ml/Kg, a PaCO2 > 60mmHg in the presence of a plateau pressure under 30cmH20 or significant acidosis are encountered (pH<7.15).
Ongoing ventilator management: Recruitment manoeuvres will be performed regularly (up to 4 times per day) until the SaO2 >/=95% on FiO2 =40% for 12 hours or FiO2 >/=35% for 1 hour. In addition the arterial pH goal for the intervention patients: 7.15 < pH < 7.45 until the SaO2 >/=95% on FiO2 =40% for 12 hours or FiO2 =35% for 1 hour.
Intervention code [1] 2069 0
Treatment: Other
Intervention code [2] 2099 0
Treatment: Other
Comparator / control treatment
The control ventilation group reflects current best practice and is based on the ARMA ARDSnet study. In brief, using volume control ventilation, inspired tidal volumes will be limited to 6mls/Kg predicted body weight (PBW), a respiratory rate of 18, a peak airway pressure of 30cmH20 and a PEEP/FiO2 Chart (ARDSnet, NEJM 2000) is followed. The arterial pH goal for control patients: 7.30 < pH < 7.45 and ventilation, tidal volume and the administration of bicarbonate will be allowed.These treamtent goals will be targeted until the SaO2 >/=95% on FiO2 =40% for 12 hours or FiO2 =35% for 1 hour.
Control group
Active

Outcomes
Primary outcome [1] 3353 0
Plasma pro-inflammatory cytokine levels (IL-6).
Timepoint [1] 3353 0
Days 0 (twice), 1, 3, 5 and 7.
Secondary outcome [1] 5570 0
Plasma pro-inflammatory cytokine levels (TNF-a, IL-1B, IL-8)
Timepoint [1] 5570 0
Day 0 (twice),1 ,3 ,5 and 7.
Secondary outcome [2] 5571 0
Length of mechanical ventilation and hospital mortality.
Timepoint [2] 5571 0
Length of mechanical ventilation censored at 28 days and hospital survival will be recorded.
Secondary outcome [3] 5572 0
PaO2/FiO2 ratios and static lung compliance. These are derived from clinical respiratory measurements including arterial blood gases, ventilation settings, peak and plateau pressure, tidal volume and PEEP.
Timepoint [3] 5572 0
At baseline, 1, 3, 6 and 24 hours and then daily during the period of mechanical ventilation
up to seven days.
Secondary outcome [4] 380763 0
ICU length of stay through recording of ICU admission and discharge date/time.
Timepoint [4] 380763 0
ICU length of stay will be recorded.
Secondary outcome [5] 380764 0
Hospital length of stay through recording of Hospital admission and discharge date/time.
Timepoint [5] 380764 0
Hospital length of stay will be recorded.

Eligibility
Key inclusion criteria
(1) Diagnosis of Acute Respiratory Distress Syndrome based on the American-European Consensus Conference criteria.
Minimum age
15 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients were excluded if they had chest trauma, an intercostal catheter with air
leak, a pneumothorax on chest x-ray, bronchospasm on auscultation, raised intracranial pressure, mean arterial pressure less than or equal to 60 mmHg, significant arrhythmias or were
ventilated for longer than 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)
Sequentially numbered opaque envelopes. Patients will be stratified based on the presence of sepsis as the precipitating cause of ARDS.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomisation matrix.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/09/2007
Actual
1/01/2008
Date of last participant enrolment
Anticipated
Actual
1/10/2009
Date of last data collection
Anticipated
Actual
1/10/2009
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 424 0
3004

Funding & Sponsors
Funding source category [1] 2604 0
Hospital
Name [1] 2604 0
Intensive Care Unit Educational Fund
Country [1] 2604 0
Australia
Primary sponsor type
Hospital
Name
Intensive Care Unit, Alfred Hospital
Address
Commercial Road
Melbourne Prahan VIC 3004
Country
Australia
Secondary sponsor category [1] 2356 0
University
Name [1] 2356 0
Australian New Zealand Intensive Care Research Center
Address [1] 2356 0
Department of Epidemiology and Preventive Medicine Monash University 553 ST KILDA RD Melbourne VIC 3004
Country [1] 2356 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4525 0
Alfred Hospital Human Ethics Committee
Ethics committee address [1] 4525 0
Commercial Road
Melbourne Prahan VIC 3004
Ethics committee country [1] 4525 0
Australia
Date submitted for ethics approval [1] 4525 0
Approval date [1] 4525 0
15/08/2007
Ethics approval number [1] 4525 0
98/07

Summary
Brief summary
This study has been designed to assess whether a ventilation strategy which maintains alveolar patency by the application of recruitment manoeuvres and elevated PEEP and which limits airway pressures by allowing permissive hypercapnia will reduce lung injury as assessed by serum cytokine levels.
Trial website
Trial related presentations / publications
A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome. Hodgson CL, Tuxen DV, Davies AR, Bailey MJ, Higgins AM, Holland AE, Keating JL, Pilcher DV, Westbrook AJ, Cooper DJ, Nichol A D.Crit Care. 2011;15(3):R133. doi: 10.1186/cc10249.PMID:21635753
Public notes

Contacts
Principal investigator
Name 28040 0
Prof Alistair Nichol
Address 28040 0
ANZIC-RC Department of Epidemiology and Preventative Medicine Monash University 553 ST KILDA RD Melbourne VIC 3004
Country 28040 0
Australia
Phone 28040 0
+61 3 99030513
Fax 28040 0
Email 28040 0
[email protected]
Contact person for public queries
Name 11197 0
Alistair Nichol
Address 11197 0
ANZIC-RC Department of Epidemiology and Preventative Medicine Monash University 553 ST KILDA RD Melbourne VIC 3004
Country 11197 0
Australia
Phone 11197 0
+61 3 99030513
Fax 11197 0
+61 3 99030556
Email 11197 0
[email protected]
Contact person for scientific queries
Name 2125 0
Alistair Nichol
Address 2125 0
ANZIC-RC Department of Epidemiology and Preventative Medicine Monash University 553 ST KILDA RD Melbourne VIC 3004
Country 2125 0
Australia
Phone 2125 0
+61 3 99030513
Fax 2125 0
+61 3 99030556
Email 2125 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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes A randomised controlled trial of an open lung stra... [More Details]

Documents added automatically
No additional documents have been identified.