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

Acute Respiratory Distress Syndrome Clinical Trial

— PHARLAP  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01667146
• Other study ID #: ANZIC-RC/AD002 Version 8
• Status: Terminated
• Phase: N/A
• Start date: October 2012
• Est. completion date: March 2018

Study information

• Verified date: November 2018
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 115
• Est. completion date: March 2018
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Hypercapnia
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Albury/Wodonga	Albury	New South Wales
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	Geelong Hospital	Geelong	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Hosptial	Melbourne	Victoria
Australia	Royal Prince Alfred	Sydney	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Ireland	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
New Zealand	Auckland City Hospital (DCCM)	Auckland
New Zealand	Auckland City Hospital CVICU	Auckland
New Zealand	Middlemore Hospital	Otahuhu	Auckland
Saudi Arabia	King Abdulaziz Medical City	Riyadh
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
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	Princess Royal University Hospital	Orpington	Kent
United Kingdom	Peterborough City Hospital	Peterborough	Cambridgeshire
United Kingdom	Derriford Hospital	Plymouth	Devon

Sponsors (1)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of ventilator free days at day 28 post randomisation		28 days post randomisation
Secondary	PaO2/FiO2 ratio and static lung compliance		Up to day 28 post randomisation
Secondary	Baseline to day 3 change in IL-8 and IL-6 concentrations in broncho-alveolar lavage and plasma		Day 3 post randomisation
Secondary	Incidence of severe hypotension		Up to 90 days post randomisation
Secondary	Incidence of barotrauma		Up to 90 days post randomisation
Secondary	Use of rescue therapies for severe hypoxaemia - inhaled nitric oxide, inhaled prostacyclin, prone positioning, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)		Within hospital admission
Secondary	Mortality	At timepoints: ICU discharge, hospital discharge, 28 days, 90 days and 6 months	Up to 6 months post randomisation
Secondary	ICU and hospital length of stay		Up to 6 months
Secondary	Incidence of AKI		Within hospital admission
Secondary	Quality of life assessment	SF36v2	6 months post randomisation
Secondary	Cost effectiveness analysis	Based on EQ-5D	6 months post randomisation