Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure

Study Overview
=================
Brief Summary
-----------------
Besides protective ventilation with low tidal volumes, prone positioning is a proven intervention to decrease mortality in mechanically ventilated patients with moderate-severe acute respiratory distress syndrome. However, the evidence of this strategy in awake non-intubated patients is scarce. The investigators will perform a randomized controlled trial to define if prone positioning can reduce the requirement of mechanical ventilation.

Detailed Description
-----------------
Despite ongoing trials of antivirals and immunomodulatory therapies against COVID-19, the treatment of moderate/severe disease is mainly supportive, including oxygen therapy and invasive mechanical ventilation when impending respiratory failure is established. Moreover, the associated mortality among mechanically intubated patients is overwhelmingly high. Prone position relieves the dependent lung regions from the compressive forces of the mediastinum's weight, leading to homogenization of the gas:tissue ratio between ventral and dorsal lung regions. According to a few case series, and observational non-randomized studies with small sample sizes, there is a consistent improvement in oxygenation in COVID-19 patients during prone positioning, however there are no clinical evidence that this improvement is associated with a decrease in the risk of invasive mechanical ventilation. Considering that prone positioning is a low cost, low risk and widely available therapy, more high quality evidence is needed, to determine if the benefits of prone positioning in awake patients also include a lower requirement of mechanical ventilation.

Official Title
-----------------
Prone Positioning in Non-intubated Patients With Severe COVID-19: a Randomized Controlled Trial

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Procedure: Awake prone positioning
* Procedure: Standard oxygen therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients with confirmed COVID-19, and requirement of a fraction of inspired oxygen (FiO2) ≥30% through high-flow nasal cannula (HFNC) to maintain a capillary saturation of ≥90% Exclusion Criteria: Less than 18 years-old Pregnancy Patients with immediate need of invasive mechanical ventilation Contraindications for prone positioning therapy Do-not-resuscitate or do-not-intubate order Refusal of the patient or decision maker to enroll in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard oxygen therapy<br>Oxygen therapy through high flow nasal cannula (HFNC). Continuous monitoring of vital signs. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Prone positioning will be allowed as a rescue therapy. | Procedure: Standard oxygen therapy<br>* Oxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%<br>|
| Experimental: Awake prone positioning<br>Oxygen therapy through high flow nasal cannula (HFNC). Patients will be asked to remain in prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. | Procedure: Awake prone positioning<br>* Patients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intubation rate |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total hours of prone position at day |  | 28 days | 
| Total number of prone sessions at day |  | 28 days | 
| Hours of the longest prone session each day |  | 28 days | 
| Change in oxygenation 1-hour after first prone session |  | 1 hour | 
| Change in the ROX-index 1-hour after first prone session | The change in the Ratio of Oxygen saturation to respiratory rate (ROX-index) | 1 hour | 
| Total days of prone positioning therapy |  | 28 days | 
| Adverse effects of prone positioning therapy |  | 28 days | 
| Mechanical ventilation days |  | 28 days | 
| Intensive care unit length of stay |  | 28 days | 
| Hospital length of stay |  | 28 days | 
| Hospital mortality |  | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Severe, Prone positioning, High-flow nasal cannula