Open Lung Ventilation in ARDS: The PHARLAP Trial

NCT ID: NCT01667146

Last Updated: 2024-07-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2018-03-31

Brief Summary

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.

Detailed Description

340 adult patients who have developed ARDS within the last 72 hours (and within 10 days of commencing mechanical ventilation) will be enrolled in 25- 30 intensive care units (ICUs) and randomly allocated to either the PHARLAP or a control ventilation strategy. PHARLAP 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 Positive-end expiratory pressure (PEEP) titration.

Control strategy: Mechanical ventilation based on the ARDSnet protocol with tidal volume 6 ml/kg, plateau pressure ≤ 30 cmH2O and fraction inspired oxygen (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. A standardised weaning from mechanical ventilation guideline will be used in both groups

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PHARLAP ventilation group

PHARLAP mechanical ventilation strategy

Group Type: EXPERIMENTAL

PHARLAP mechanical ventilation strategy

Intervention Type: OTHER

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.

Control group ventilation

Control group mechanical ventilation strategy

Group Type: ACTIVE_COMPARATOR

Control group mechanical ventilation strategy

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

Eligibility 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 chest x-ray (CXR) which are not fully explained by effusions, lobar/lung collapse or nodules
• Respiratory failure not fully explained by cardiac failure or fluid overload
• Arterial oxygen pressure (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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College Dublin

OTHER

Sponsor Role: collaborator

Australian and New Zealand Intensive Care Research Centre

OTHER

Sponsor Role: lead

Responsible Party

Carol Hodgson

Dr Carol Hodgson

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carol Hodgson, PhD, FACP, BAppSc

Role: STUDY_CHAIR

Australian and New Zealand Intensive Care Research Centre (ANZIC-RC)

Alistair Nichol, PhD, FCICM

Role: STUDY_CHAIR

Australian and New Zealand Intensive Care Research Centre (ANZIC-RC)

Locations

Albury/Wodonga

Albury, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Royal Prince Alfred

Sydney, New South Wales, Australia

Wollongong Hospital

Wollongong, New South Wales, Australia

The Prince Charles Hospital

Brisbane, Queensland, Australia

Flinders Medical Centre

Adelaide, South Australia, Australia

Geelong Hospital

Geelong, Victoria, Australia

The Alfred Hosptial

Melbourne, Victoria, Australia

Adelaide and Meath (Tallaght) Hospital

Dublin, , Ireland

Beaumont Hospital

Dublin, , Ireland

Mater Misericordiae University Hospital

Dublin, , Ireland

St Vincents Hospital

Dublin, , Ireland

University Hospital Limerick

Limerick, , Ireland

Middlemore Hospital

Otahuhu, Auckland, New Zealand

Auckland City Hospital (DCCM)

Auckland, , New Zealand

Auckland City Hospital CVICU

Auckland, , New Zealand

King Abdulaziz Medical City

Riyadh, , Saudi Arabia

Peterborough City Hospital

Peterborough, Cambridgeshire, United Kingdom

Derriford Hospital

Plymouth, Devon, United Kingdom

Princess Royal University Hospital

Orpington, Kent, United Kingdom

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Southmead Hospital

Bristol, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

King's College Hospital

London, , United Kingdom

North Middlesex University Hospital

London, , United Kingdom

University Hospital, Lewisham

London, , United Kingdom

James Cook University Hospital

Middlesbrough, , United Kingdom

Countries

Australia; Ireland; New Zealand; Saudi Arabia; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 31356105 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29852853 (View on PubMed)

Bihari S, Bersten A, Paul E, McGuinness S, Dixon D, Sinha P, Calfee CS, Nichol A, Hodgson C; PHARLAP Study Investigators. Acute respiratory distress syndrome phenotypes with distinct clinical outcomes in PHARLAP trial cohort. Crit Care Resusc. 2023 Oct 18;23(2):163-170. doi: 10.51893/2021.2.oa3. eCollection 2021 Jun.

Reference Type: BACKGROUND

PMID: 38045528 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

ANZIC-RC/AD002 Version 8

Identifier Type: -

Identifier Source: org_study_id