Open Lung Ventilation in ARDS: The PHARLAP Trial

Australian and New Zealand Intensive Care Research Centre

Status: Terminated

Conditions: Acute Respiratory Distress Syndrome

Treatments: Other: PHARLAP mechanical ventilation strategy; Other: Control group mechanical ventilation strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT01667146

ANZIC-RC/AD002 Version 8

Details and patient eligibility

About

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.

Full 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

Enrollment: 115 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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115 participants in 2 patient groups

PHARLAP ventilation group

Experimental group

Description:

PHARLAP mechanical ventilation strategy

Treatment:

Other: PHARLAP mechanical ventilation strategy

Control group ventilation

Active Comparator group

Description:

Control group mechanical ventilation strategy

Treatment:

Other: Control group mechanical ventilation strategy