An interventional study of PHARLAP mechanical ventilation strategy and Control group mechanical ventilation strategy in Acute Respiratory Distress Syndrome, sponsored by Australian and New Zealand Intensive Care Research Centre. Terminated at 27 sites in 5 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2024-07-18.
Sponsored by Australian and New Zealand Intensive Care Research Centre · Not applicable, Interventional, and Treatment
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.
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
1,597 studies on the registry are indexed under Respiratory Distress Syndrome; 312 are open to participants now.
This study's enrollment of 115 is above the median of 60 across 961 interventional studies indexed under Respiratory Distress Syndrome.
Browse Respiratory Distress Syndrome studies →Australian and New Zealand Intensive Care Research Centre is the lead sponsor of 48 studies on the registry; 16 are open to participants now.
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Adult ICU patients who met all of the following criteria:
Exclusion Criteria:
PHARLAP mechanical ventilation strategy
Other: PHARLAP mechanical ventilation strategy
Control group mechanical ventilation strategy
Other: Control group 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.
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.
Number of Ventilator Free Days at Day 28 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).
Time frame: 28 days post randomisation
PaO2/FiO2 Ratio and Static Lung Compliance
PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage). ARDS severity Mild 200-300 / Moderate 100-200 / Severe \<100.
Time frame: Up to day 28 post randomisation
Baseline to Day 3 Change in IL-8 and IL-6 Concentrations in Broncho-alveolar Lavage and Plasma
IL-8 is an important protein related to inflammation, Interleukin (IL)-6 is produced at the site of inflammation and plays a key role in the acute phase response
Time frame: Day 3 post randomisation
Number of Severe Hypotension Events
Hypotension requiring increased vasopressor Days 1-28
Time frame: Up to 28 days post randomisation
Number of Participants With Barotrauma
Evidence of Pneumothorax requiring Drainage
Time frame: 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)
The use of various rescue therapies (each of the therapies is compared between groups - per patient). the various therapies measured are inhaled nitric oxide, inhaled prostacyclin, prone positioning, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)
Time frame: Within hospital admission
Mortality
At timepoints: day 28
Time frame: at day 28
ICU Length of Stay
The number of days a person stayed in the ICU. A fraction of a day is considered a day
Time frame: From admission to ICU up to 6 months
Incidence of Acute Kidney Injury (AKI)
The incidence of Acute Renal Injury - measured by the use of Continuous Renal Replacement Therapy (CRRT) in each person
Time frame: Within hospital admission
Quality of Life Assessment
SF36v2 will be used Medical Outcomes Study. Scoring the RAND is a two-step process. First, pre-coded numeric values are recoded. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores.
Time frame: 6 months post randomisation
Cost Effectiveness Analysis
This will be based on EQ-5D. EQ-5D is the most widely used health-related quality of life questionnaire in health economic evaluations.\[62\] EQ-5D can be used to derive a set of values that reflect people's opinions of the relative importance of different health problems. These values can be used to derive QALYs for application in cost-effectiveness and cost-utility evaluations.
Time frame: 6 months post randomisation
Hospital Length of Stay
The length of time in days a participant stayed in hospital. A fraction of a day is considered 1 day.
Time frame: From admission up to 6 months
| Milestone | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Started | 58 | 57 |
| Completed | 57 | 56 |
| Not completed | 1 | 1 |
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).
| days | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Number of Ventilator Free Days at Day 28 Post Randomisation | 16 (0 to 21) | 14.5 (0 to 21.5) |
PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage). ARDS severity Mild 200-300 / Moderate 100-200 / Severe \<100.
Results for this outcome have not been posted.
IL-8 is an important protein related to inflammation, Interleukin (IL)-6 is produced at the site of inflammation and plays a key role in the acute phase response
Results for this outcome have not been posted.
Hypotension requiring increased vasopressor Days 1-28
| events | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Number of Severe Hypotension Events | 20 | 12 |
Evidence of Pneumothorax requiring Drainage
| Participants | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Number of Participants With Barotrauma | 3 | 2 |
The use of various rescue therapies (each of the therapies is compared between groups - per patient). the various therapies measured are inhaled nitric oxide, inhaled prostacyclin, prone positioning, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)
Results for this outcome have not been posted.
At timepoints: day 28
| Participants | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Mortality | 14 | 15 |
The number of days a person stayed in the ICU. A fraction of a day is considered a day
| days | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| ICU Length of Stay | 11.1 (6.2 to 20.1) | 13.8 (6.8 to 22.5) |
The incidence of Acute Renal Injury - measured by the use of Continuous Renal Replacement Therapy (CRRT) in each person
Results for this outcome have not been posted.
SF36v2 will be used Medical Outcomes Study. Scoring the RAND is a two-step process. First, pre-coded numeric values are recoded. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores.
Results for this outcome have not been posted.
This will be based on EQ-5D. EQ-5D is the most widely used health-related quality of life questionnaire in health economic evaluations.\[62\] EQ-5D can be used to derive a set of values that reflect people's opinions of the relative importance of different health problems. These values can be used to derive QALYs for application in cost-effectiveness and cost-utility evaluations.
Results for this outcome have not been posted.
The length of time in days a participant stayed in hospital. A fraction of a day is considered 1 day.
| Days | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Hospital Length of Stay | 20.1 (8.1 to 37.2) | 17.9 (9.0 to 39.0) |
Collected over Adverse events will be collected from randomisation up until the 90 day follow up, up to 90 days in total. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PHARLAP Ventilation Group | 14/57 (24.6%) | 23/58 (39.7%) | 9/58 (15.5%) |
| Control Group Ventilation | 17/56 (30.4%) | 15/56 (26.8%) | 4/56 (7.1%) |
| Event | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| Severe HypotensionCardiac disorders | 20/58 | 12/56 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 3/58 | 3/56 |
| Event | PHARLAP Ventilation Group | Control Group Ventilation |
|---|---|---|
| refractory acidosisMetabolism and nutrition disorders | 9/58 | 4/56 |
| Age, Continuous(years) | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|
| Mean | 54.2 ± 14.0 | 53.2 ± 14.4 | 53.7 ± 14.2 |
| Sex: Female, Male(Participants) | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|
| Female | 22 | 26 | 48 |
| Male | 36 | 30 | 66 |
| Race and Ethnicity Not Collected(Participants) | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| APACHE II score(units on a scale) | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|
| Median | 23.2 ± 6.8 | 22.3 ± 7.7 | 22.8 ± 7.2 |
| BMI(kg/m^2) | PHARLAP Intervention Arm | Control Group | Total |
|---|---|---|---|
| Mean | 31.3 ± 10.1 | 30.3 ± 7.2 | 30.8 ± 8.6 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — The Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Monash University supports the view that: * Publicly funded research data should be made available with as few restrictions as possible * Data sharing could enhance public well-being by maximising utilisation of gained knowledge, reducing redundant research and facilitating scientific innovation, * Data sharing must be responsible, recognise legal, regulatory, ethical and commercial constraints. The ANZIC-RC has formulated a policy and process to allow appropriate and responsible sharing of research data including prospective and completed studies. This Policy was guided by, Institute of Medicine principles for responsible sharing of clinical trial data: * Maximise the benefits of clinical trials * Minimising the risks of data sharing * Respect individual participants * Increase public trust in clinical trials * Conduct the sharing of trial data in a fair manner * Appropriately manage conflicts of interest.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
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