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.
Overview
- Phase
- Not Applicable
- Status
- Terminated
- Enrollment
- 115
- Locations
- 27
- Primary Endpoint
- Number of Ventilator Free Days at Day 28 Post Randomisation
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Number of Ventilator Free Days at Day 28 Post Randomisation
Time Frame: 28 days post randomisation
This is the total number of days calculated from day 1 (randomisation) to day 28 on which the patient was alive and received no assistance from invasive mechanical ventilation. Scores range between 0 (no ventilator free days) to 28 (no days on ventilator).
Secondary Outcomes
- PaO2/FiO2 Ratio and Static Lung Compliance(Up to day 28 post randomisation)
- Baseline to Day 3 Change in IL-8 and IL-6 Concentrations in Broncho-alveolar Lavage and Plasma(Day 3 post randomisation)
- ICU Length of Stay(From admission to ICU up to 6 months)
- Number of Severe Hypotension Events(Up to 28 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)(Within hospital admission)
- Incidence of Acute Kidney Injury (AKI)(Within hospital admission)
- Hospital Length of Stay(From admission up to 6 months)
- Number of Participants With Barotrauma(Up to 90 days post randomisation)
- Mortality(at day 28)
- Quality of Life Assessment(6 months post randomisation)
- Cost Effectiveness Analysis(6 months post randomisation)
Investigators
Carol Hodgson
Dr Carol Hodgson
Australian and New Zealand Intensive Care Research Centre