HYPoxaEmic Respiratory Failure and Awake Prone Ventilation

Study Overview
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Brief Summary
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The goal of this prospective multi-centre randomised controlled trial is to determine if addition of awake prone positioning to standard oxygen, high flow oxygen therapy and non-invasive ventilation may reduce the rates of endotracheal intubation and mechanical ventilation.

Detailed Description
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Effectiveness of prone position in mechanically ventilated patients was investigated extensively. During the Covid-19 pandemic a sudden increase in cases of acute respiratory failure, resulted in renewed interest and numerous studies on applying this concept in spontaneously breathing patients and using this in conjunction with less invasive respiratory support. However, evidence form the Covid-19 trials may not be directly extrapolated to other acute respiratory distress causes (for example bacterial pneumonia) as pathology of lung injury is distinctly different. Even though first reports of awake prone positioning were published nearly 30 years ago, but to date there are no prospective randomised trials in adult population treated for acute lung injury unrelated to Covid-19. Existing publications range from case reports (lung transplantation and drowning cases) to small feasibility trials involving 15-20 patients and also neonatal and paediatric populations. Considering that patients with acute lung injury constitute a significant proportion of routine intensive care unit population, results of this study would be highly relevant for the daily practice in intensive care medicine.We are aiming to conduct a prospective multi-centre randomised controlled trial comparing standard care alone with awake prone positioning and standard care in spontaneously breathing patients admitted to Intensive or Intermediate Care Units for acute non-Covid-19 hypoxemic respiratory failure.

Official Title
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HYPoxaEmic Respiratory Failure and Awake Prone Ventilation

Conditions
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Respiratory Failure, Hypoxemia

Intervention / Treatment
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* Behavioral: Awake prone position (APP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients admitted to intensive care unit for acute hypoxemic respiratory failure. Acute hypoxemic respiratory failure is defined by respiratory rate ≥25 breaths/min, and partial pressure of oxygen in the arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ≤300 mm Hg or oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio <235 while spontaneously breathing under standard oxygen with oxygen flow rate of at least 10 L/min, high flow oxygen therapy or non-invasive ventilation. For patients under standard oxygen, FiO2 is calculated according to the following formula: FiO2=0.21 + 0.03 per litre of supplemental oxygen. Informed consent Exclusion Criteria: impaired consciousness - Glasgow coma score <14; inability to cooperate or prone position intolerance; immediate indications for endotracheal intubation; patients with do-not-intubate order at time of inclusion; patients with contraindication to high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV); Partial pressure of carbon dioxide (PaCO2) above 50 mm Hg and quantitative measure of the acidity (pH) <7,3; vasopressor dose >0.3 µg/kg/min of norepinephrine-equivalent to maintain systolic blood pressure >90 mmHg; Covid-19 positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be allocated to the awake prone or standard care groups on a 1:1 ratio.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APP group<br>Awake prone position (APP) for 4 or more hours per day in addition to standard care for the first 72 hours from randomisation. After the initial period, use of APP is at discretion of the treating clinician. Awake prone can be discontinued earlier if patients meets pre-specified criteria of sustained improvement. | Behavioral: Awake prone position (APP)<br>* Awake prone position for 4 or more hours per day for the first 72 hours following randomisation.<br>|
| No Intervention: Control group<br>Standard care excluding APP | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of endotracheal intubation | Incidence of endotracheal intubation in both groups | Within 30 days of randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality during intensive care unit stay, in hospital, at day 90 and at 1 year | Within 1 year of randomisation | 
| Duration of mechanical ventilation | Total number of mechanical ventilation days from endotracheal intubation to discharge from intensive care unit | Within 30 days of randomisation | 
| Length of intensive care unit and hospital stay | Total cumulative number of days spent in intensive care unit and hospital | Within 30 days of randomisation | 
| One year mortality | Incidence or death during one year of randomisation | Within 1 year of randomisation | 
| Health related quality of life | Heath related quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) one year of randomisation | Within 1 year of randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Awake prone, Respiratory failure, ARDS, Hypoxaemia