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 May 2013 by Australian and New Zealand Intensive Care Research Centre
Sponsor:
Australian and New Zealand Intensive Care Research Centre
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: May 6, 2013
Last verified: May 2013
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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
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 | Not yet 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 | Not yet recruiting |
| Wollongong, New South Wales, Australia, 2500 | |
| Contact: Alan Davey-Quinn | |
| Australia, Queensland | |
| The Prince Charles Hospital | Not yet 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 | Not yet 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 | 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 4 |
| Study First Received: | August 12, 2012 |
| Last Updated: | May 6, 2013 |
| Health Authority: | Australia: Human Research Ethics Committee Australia: National Health and Medical Research Council |
Additional relevant MeSH terms:
|
Hypercapnia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Signs and Symptoms, Respiratory Signs and Symptoms |
Lung Diseases Respiratory Tract Diseases Respiration Disorders Infant, Premature, Diseases Infant, Newborn, Diseases Lung Injury |
ClinicalTrials.gov processed this record on May 22, 2013