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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.
Verified September 2017 by Carol Hodgson, Australian and New Zealand Intensive Care Research Centre
Sponsor:
ClinicalTrials.gov Identifier:
NCT01667146
First Posted: August 17, 2012
Last Update Posted: September 8, 2017
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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Carol Hodgson, Australian and New Zealand Intensive Care Research Centre
  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
Intervention Model: Parallel Assignment
Masking: None (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 Carol Hodgson, 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 ]

Secondary Outcome Measures:
  • PaO2/FiO2 ratio and static lung compliance [ Time Frame: Up to day 28 post randomisation ]
  • Baseline to day 3 change in IL-8 and IL-6 concentrations in broncho-alveolar lavage and plasma [ Time Frame: Day 3 post randomisation ]
  • Incidence of severe hypotension [ Time Frame: Up to 90 days post randomisation ]
  • Incidence of barotrauma [ Time Frame: Up to 90 days post randomisation ]
  • 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 ]
  • Mortality [ Time Frame: Up to 6 months post randomisation ]
    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 ]
  • Incidence of AKI [ Time Frame: Within hospital admission ]
  • Quality of life assessment [ Time Frame: 6 months post randomisation ]
    SF36v2

  • Cost effectiveness analysis [ Time Frame: 6 months post randomisation ]
    Based on EQ-5D


Estimated Enrollment: 340
Study Start Date: October 2012
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: December 2017 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult ICU patients who met all of the following criteria:

  • Currently intubated and receiving mechanical ventilation
  • Within 72 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:

  • > 72 hours since diagnosis of ARDS
  • > 10 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
  • Clinical suspicion for significant restrictive lung disease (history of pulmonary fibrosis or suggestive pulmonary function tests)
  • 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
  • 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01667146


Contacts
Contact: Meredith E Young +61 399030280 meredith.young@monash.edu

Locations
Australia, New South Wales
Nepean Hospital Recruiting
Kingswood, New South Wales, Australia, 2747
Contact: Ian Seppelt         
Royal Prince Alfred Recruiting
Sydney, New South Wales, Australia
Contact: Richard Totaro         
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         
Australia, Victoria
Albury/Wodonga Recruiting
Albury, Victoria, Australia
Contact: David Tuxen         
Geelong Hospital Recruiting
Geelong, Victoria, Australia, 3220
Contact: Neil Orford         
The Alfred Hosptial Recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: David Tuxen         
Ireland
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: Ger Curley         
Mater Misericordiae University Hospital Recruiting
Dublin, Ireland
Contact: Colman O'Loughlin         
St Vincents Hospital Recruiting
Dublin, Ireland
Contact: Alistair Nichol         
New Zealand
Middlemore Hospital Recruiting
Otahuhu, Auckland, New Zealand, 1640
Contact: Anthony Williams         
Auckland City Hospital (DCCM) Recruiting
Auckland, New Zealand, 1142
Contact: Colin McArthur         
Auckland City Hospital CVICU Recruiting
Auckland, New Zealand, 1142
Contact: Shay McGuinness         
Saudi Arabia
King Abdulaziz Medical City Recruiting
Riyadh, Saudi Arabia
Contact: Yaseen Arabi         
United Kingdom
Peterborough City Hospital Recruiting
Peterborough, Cambridgeshire, United Kingdom
Contact: Coralie Carle         
Derriford Hospital Recruiting
Plymouth, Devon, United Kingdom
Contact: Peter MacNaughton         
Princess Royal University Hospital Recruiting
Orpington, Kent, United Kingdom
Contact: Tom Williams         
Royal Surrey County Hospital Recruiting
Guildford, Surrey, United Kingdom
Contact: Mehrun Zuleika         
Southmead Hospital Recruiting
Bristol, United Kingdom
Contact: Matt Thomas         
Hull Royal Infirmary Recruiting
Hull, United Kingdom
Contact: Andrew Gratrix         
King's College Hospital Recruiting
London, United Kingdom
Principal Investigator: Phil Hopkins         
North Middlesex University Hospital Recruiting
London, United Kingdom
Contact: Jeronimo Moreno Cuesta         
University Hospital, Lewisham Recruiting
London, United Kingdom
Contact: Mick Jennings         
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

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 8
First Submitted: August 12, 2012
First Posted: August 17, 2012
Last Update Posted: September 8, 2017
Last Verified: September 2017

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