A Multi-centre Trial of an Open Lung Strategy Including Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure in Patients With Acute Respiratory Distress Syndrome (PHARLAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Australian and New Zealand Intensive Care Research Centre
Sponsor:
Information provided by (Responsible Party):
Carol Hodgson, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier:
NCT01667146
First received: August 12, 2012
Last updated: December 1, 2013
Last verified: December 2013
  Purpose

Some people develop the condition called acute respiratory distress syndrome (ARDS). This is a condition where the lungs have become injured from one of a number of various causes, and do not work as they normally do to provide oxygen and remove carbon dioxide from the body. This can lead to a reduced amount of oxygen in the patient's bloodstream. Patients with ARDS are admitted to the intensive care unit (ICU) and need help with their breathing by being connected to a ventilator (breathing machine). ARDS can lead to injury in other organs of the body causing other problems but also death.

Over the past few years, reducing the size of each breath delivered by the ventilator in conjunction with the use of an occasional sustained deep breath called a "recruitment manoeuvre" have been used to try to prevent further damage to the lungs in people with ARDS. This ventilator strategy (termed the PHARLAP strategy) has been shown in a small research study to have some beneficial effects without causing any obvious harm, when compared to a current best practice ventilator strategy. The main beneficial effects of the PHARLAP strategy were to increase the amount of oxygen in the blood and to reduce markers of inflammation (the body reacting to a disease process) in the body. This study was too small to make a strong conclusion, so this study will be much larger and will assess whether patients who have developed ARDS are better off when we use the PHARLAP strategy. Three hundred and forty patients will be enrolled into this study in multiple ICUs across Australia and New Zealand.

The study hypothesis is that the PHARLAP strategy group will have a higher number of ventilator free days at day 28 than the control group.


Condition Intervention
Acute Respiratory Distress Syndrome
Other: PHARLAP mechanical ventilation strategy
Other: Control group mechanical ventilation strategy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-centre Randomised Controlled Trial of an Open Lung Strategy Including Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure in Patients With Acute Respiratory Distress Syndrome.

Resource links provided by NLM:


Further study details as provided by Australian and New Zealand Intensive Care Research Centre:

Primary Outcome Measures:
  • Number of ventilator free days at day 28 post randomisation [ Time Frame: 28 days post randomisation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PaO2/FiO2 ratio and static lung compliance [ Time Frame: Up to day 28 post randomisation ] [ Designated as safety issue: No ]
  • Baseline to day 3 change in IL-8 and IL-6 concentrations in broncho-alveolar lavage and plasma [ Time Frame: Day 3 post randomisation ] [ Designated as safety issue: No ]
  • Incidence of severe hypotension [ Time Frame: Up to 90 days post randomisation ] [ Designated as safety issue: Yes ]
  • Incidence of barotrauma [ Time Frame: Up to 90 days post randomisation ] [ Designated as safety issue: Yes ]
  • Use of rescue therapies for severe hypoxaemia - inhaled nitric oxide, inhaled prostacyclin, prone positioning, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO) [ Time Frame: Within hospital admission ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: Up to 6 months post randomisation ] [ Designated as safety issue: No ]
    At timepoints: ICU discharge, hospital discharge, 28 days, 90 days and 6 months

  • ICU and hospital length of stay [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Incidence of AKI [ Time Frame: Within hospital admission ] [ Designated as safety issue: No ]
  • Quality of life assessment [ Time Frame: 6 months post randomisation ] [ Designated as safety issue: No ]
    SF36v2

  • Cost effectiveness analysis [ Time Frame: 6 months post randomisation ] [ Designated as safety issue: No ]
    Based on EQ-5D


Estimated Enrollment: 340
Study Start Date: October 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PHARLAP ventilation group
PHARLAP mechanical ventilation strategy
Other: PHARLAP mechanical ventilation strategy
Pressure control ventilation to maintain tidal volume 4-6 ml/kg and plateau pressure ≤ 30 cmH2O while tolerating respiratory acidosis if pH > 7.15; daily staircase recruitment manoeuvre and individualised PEEP titration.
Active Comparator: Control group ventilation
Control group mechanical ventilation strategy
Other: Control group mechanical ventilation strategy
Mechanical ventilation based on the ARDSnet protocol using volume control ventilation with tidal volume 6 ml/kg, plateau pressure ≤ 30 cmH2O and FiO2/PEEP titration according to a FiO2/PEEP/oxygen saturation combination chart. This has been modified for Australian and New Zealand practice to allow pressure control and pressure support ventilation.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult ICU patients who met all of the following criteria:

  • Currently intubated and receiving mechanical ventilation
  • Within 48 Hours of a diagnosis of ARDS (moderate and severe) based on the following Berlin definition:
  • Within 1 week of a known clinical insult or new or worsening respiratory symptoms
  • Bilateral opacities on CXR which are not fully explained by effusions, lobar/lung collapse or nodules
  • Respiratory failure not fully explained by cardiac failure or fluid overload
  • PaO2/FiO2 < 200mmHg with PEEP ≥ 5cmH2O

Exclusion Criteria:

  • > 48 hours since diagnosis of ARDS
  • > 5 days of continuous mechanical ventilation
  • Barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema or any intercostal catheter for the treatment of air leak)
  • Significant chest trauma i.e. multiple rib fractures
  • Active bronchospasm or a history of significant chronic obstructive pulmonary disease or asthma
  • Moderate or severe traumatic brain injury, the presence of an intracranial pressure monitor, or any medical condition associated with a clinical suspicion of raised intracranial pressure
  • Unstable cardiovascular status defined as sustained heart rate < 40 or > 140 bpm, ventricular tachycardia, or SBP < 80mmHg
  • Pregnancy
  • Receiving ECMO
  • Receiving high frequency oscillatory ventilation
  • Has received a staircase recruitment manoeuvre for this episode of ARDS
  • Death is deemed imminent and inevitable
  • The treating physician believes it is not in the best interest of the patient to be enrolled in the trial
  • Consent not obtained or refused by patient's legal surrogate
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01667146

Contacts
Contact: Victoria L Bennett +61 399030280 victoria.bennett@monash.edu

Locations
Australia, New South Wales
Nepean Hospital Recruiting
Kingswood, New South Wales, Australia, 2747
Contact: Ian Seppelt         
John Hunter Hospital Not yet recruiting
New Lambton, New South Wales, Australia, 2306
Contact: Peter Harrigan         
Wollongong Hospital Recruiting
Wollongong, New South Wales, Australia, 2500
Contact: Alan Davey-Quinn         
Australia, Queensland
The Prince Charles Hospital Recruiting
Brisbane, Queensland, Australia
Contact: John Fraser         
Australia, South Australia
Flinders Medical Centre Recruiting
Adelaide, South Australia, Australia
Contact: Andrew Bersten         
Lyell McEwin Hospital Recruiting
Elizabeth Vale, South Australia, Australia, 5112
Contact: Peter Thomas         
Australia, Victoria
The Northern Hospital Recruiting
Epping, Victoria, Australia, 3076
Contact: Angaj Ghosh         
Western Hospital Not yet recruiting
Footscray, Victoria, Australia, 3011
Contact: Craig French         
Geelong Hospital Not yet recruiting
Geelong, Victoria, Australia, 3220
Contact: Neil Orford         
Austin Health Not yet recruiting
Heidelberg, Victoria, Australia, 3132
Contact: Rinaldo Bellomo         
The Alfred Hosptial Recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: David Tuxen         
New Zealand
Middlemore Hospital Recruiting
Otahuhu, Auckland, New Zealand, 1640
Contact: Anthony Williams         
Auckland City Hospital CVICU Recruiting
Auckland, New Zealand, 1142
Contact: Shay McGuinness         
Auckland City Hospital (DCCM) Recruiting
Auckland, New Zealand, 1142
Contact: Colin McArthur         
Canterbury District Health Board Not yet recruiting
Christchurch, New Zealand, 8140
Contact: Seton Henderson         
Wellington Hospital Recruiting
Wellington, New Zealand, 6242
Contact: Paul Young         
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
Investigators
Study Chair: Carol Hodgson, PhD, FACP, BAppSc (Physio) Australian and New Zealand Intensive Care Research Centre (ANZIC-RC)
Study Chair: Alistair Nichol, PhD, FCICM Australian and New Zealand Intensive Care Research Centre (ANZIC-RC)
  More Information

No publications provided

Responsible Party: Carol Hodgson, Dr Carol Hodgson, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT01667146     History of Changes
Other Study ID Numbers: ANZIC-RC/AD002 Version 7
Study First Received: August 12, 2012
Last Updated: December 1, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council

Additional relevant MeSH terms:
Acute Lung Injury
Hypercapnia
Respiratory Distress Syndrome, Adult
Respiratory Distress Syndrome, Newborn
Syndrome
Disease
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Lung Injury
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory

ClinicalTrials.gov processed this record on October 21, 2014