- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01667146
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)
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.
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
New South Wales
-
Albury, New South Wales, Australia
- Albury/Wodonga
-
Kingswood, New South Wales, Australia, 2747
- Nepean Hospital
-
Sydney, New South Wales, Australia
- Royal Prince Alfred
-
Wollongong, New South Wales, Australia, 2500
- Wollongong Hospital
-
-
Queensland
-
Brisbane, Queensland, Australia
- The Prince Charles Hospital
-
-
South Australia
-
Adelaide, South Australia, Australia
- Flinders Medical Centre
-
-
Victoria
-
Geelong, Victoria, Australia, 3220
- Geelong Hospital
-
Melbourne, Victoria, Australia, 3004
- The Alfred Hosptial
-
-
-
-
-
Dublin, Ireland
- Beaumont Hospital
-
Dublin, Ireland
- Mater Misericordiae University Hospital
-
Dublin, Ireland
- St Vincents Hospital
-
Dublin, Ireland
- Adelaide and Meath (Tallaght) Hospital
-
Limerick, Ireland
- University Hospital Limerick
-
-
-
-
-
Auckland, New Zealand, 1142
- Auckland City Hospital (DCCM)
-
Auckland, New Zealand, 1142
- Auckland City Hospital CVICU
-
-
Auckland
-
Otahuhu, Auckland, New Zealand, 1640
- Middlemore Hospital
-
-
-
-
-
Riyadh, Saudi Arabia
- King Abdulaziz Medical City
-
-
-
-
-
Bristol, United Kingdom
- Southmead Hospital
-
Hull, United Kingdom
- Hull Royal Infirmary
-
London, United Kingdom
- North Middlesex University Hospital
-
London, United Kingdom
- King's College Hospital
-
London, United Kingdom
- University Hospital, Lewisham
-
Middlesbrough, United Kingdom
- James Cook University Hospital
-
-
Cambridgeshire
-
Peterborough, Cambridgeshire, United Kingdom
- Peterborough City Hospital
-
-
Devon
-
Plymouth, Devon, United Kingdom
- Derriford Hospital
-
-
Kent
-
Orpington, Kent, United Kingdom
- Princess Royal University Hospital
-
-
Surrey
-
Guildford, Surrey, United Kingdom
- Royal Surrey County Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PHARLAP ventilation group
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of ventilator free days at day 28 post randomisation
Time Frame: 28 days post randomisation
|
28 days post randomisation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PaO2/FiO2 ratio and static lung compliance
Time Frame: Up to day 28 post randomisation
|
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
|
Day 3 post randomisation
|
|
Incidence of severe hypotension
Time Frame: Up to 90 days post randomisation
|
Up to 90 days post randomisation
|
|
Incidence of barotrauma
Time Frame: Up to 90 days post randomisation
|
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
|
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
|
Up to 6 months post randomisation
|
ICU and hospital length of stay
Time Frame: Up to 6 months
|
Up to 6 months
|
|
Incidence of AKI
Time Frame: Within hospital admission
|
Within hospital admission
|
|
Quality of life assessment
Time Frame: 6 months post randomisation
|
SF36v2
|
6 months post randomisation
|
Cost effectiveness analysis
Time Frame: 6 months post randomisation
|
Based on EQ-5D
|
6 months post randomisation
|
Collaborators and Investigators
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)
Publications and helpful links
General Publications
- Hodgson CL, Cooper DJ, Arabi Y, King V, Bersten A, Bihari S, Brickell K, Davies A, Fahey C, Fraser J, McGuinness S, Murray L, Parke R, Paul E, Tuxen D, Vallance S, Young M, Nichol A. Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP). A Phase II, Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1363-1372. doi: 10.1164/rccm.201901-0109OC.
- Hodgson C, Cooper DJ, Arabi Y, Bennett V, Bersten A, Brickell K, Davies A, Fahey C, Fraser J, McGuinness S, Murray L, Parke R, Tuxen D, Vallance S, Young M, Nichol AD; PHARLAP Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure (PHARLAP): a protocol for a phase 2 trial in patients with acute respiratory distress syndrome. Crit Care Resusc. 2018 Jun;20(2):139-149.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ANZIC-RC/AD002 Version 8
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Respiratory Distress Syndrome
-
Tanta UniversityRecruitingAcute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) | Respiratory Distress Syndrome, PediatricEgypt
-
University Hospital, Clermont-FerrandWithdrawn
-
China-Japan Friendship HospitalNot yet recruitingAcute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
-
Dr. Behcet Uz Children's HospitalRecruitingAcute Respiratory Distress Syndrome | Acute Respiratory Failure | Pediatric Acute Respiratory Distress Syndrome (PARDS)Turkey
-
Assistance Publique - Hôpitaux de ParisCompletedSevere Acute Respiratory Syndrome Coronavirus 2 | Severe Acute Respiratory Distress SyndromeFrance
-
Aqualung Therapeutics Corp.Not yet recruitingAcute Respiratory Distress Syndrome (ARDS)
-
Unity Health TorontoRecruitingAcute Respiratory Distress Syndrome (ARDS)Canada, Spain, Italy, Brazil
-
Western University, CanadaEnrolling by invitationCOVID-19 Acute Respiratory Distress SyndromeCanada
-
Ain Shams UniversityCompletedCOVID-19 Acute Respiratory Distress SyndromeEgypt
-
Hospices Civils de LyonTerminatedAcute Respiratory Distress Syndrome (ARDS)France
Clinical Trials on PHARLAP mechanical ventilation strategy
-
Beth Israel Deaconess Medical CenterNational Heart, Lung, and Blood Institute (NHLBI)CompletedAcute Respiratory Distress SyndromeUnited States, Canada
-
Assiut UniversityNot yet recruiting
-
University Health Network, TorontoRecruitingCardiac Surgery | Pulmonary ComplicationsCanada
-
Beijing Chao Yang HospitalRecruiting
-
United States Army Institute of Surgical ResearchTerminated
-
Affiliated Hospital of Nantong UniversityEnrolling by invitationTumor MicroenvironmentChina
-
Rui WangCompletedRespiratory Distress Syndrome, AdultChina
-
Peking Union Medical College HospitalThe First Affiliated Hospital with Nanjing Medical University; National Natural... and other collaboratorsUnknownAcute Respiratory Failure | Immunocompromised Patients
-
Ruijin HospitalUnknownAcute Pancreatitis | Complication of Ventilation TherapyChina
-
Azienda Ospedaliero Universitaria Maggiore della...CompletedSurgery | Atelectasis | Artificial RespirationItaly