Prone Position in Patients on High-flow Nasal Oxygen Therapy for COVID-19 (HIGH-PRONE-COVID-19)

Study Overview
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Brief Summary
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Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. Preliminary data from patients with ARDS related to COVID-19 disease appear to show significant effectiveness of prone positioning in intubated patients in terms of oxygenation as well as nasal high flow therapy before intubation. It should be noted that in Jiangsu province, secondarily affected, nasal high flow combined with the prone position was successfully integrated into care protocols. The investigators hypothesize that the combined application of nasal high flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for tracheal intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources. Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

Detailed Description
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Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. In patients with ARDS who are mechanically ventilated invasively through a tracheal tube and with a PaO2/FiO2 ratio (arterial oxygen partial pressure to inspired oxygen fraction ratio) of less than 150 mmHg, prone positioning significantly reduced mortality. Furthermore, nasal high flow, a non-invasive respiratory support and oxygenation technique, reduced the need for tracheal intubation and reduced mortality among the most severe patients (PaO2/FiO2 ratio less than 200 mmHg) suffering from acute hypoxemic respiratory failure. Prone positioning of ARDS patients treated with nasal high-flow was evaluated in 20 patients with predominantly viral pneumonia. The prone positioning was found to be feasible and associated with an increased PaO2/FiO2 ratio. Preliminary data from patients with ARDS related to COVID-19 disease appear to show a significant effect of prone positioning in intubated patients in terms of oxygenation improvement as well as nasal high-high flow appears effective in non-intubated patients. For instance, nearly half intensive care unit patients described in the princeps cohort in Wuhan City, Hubei Province, China, had received nasal high-flow. It should be noted that in Jiangsu province, secondarily affected, nasal high-flow combined with prone positioning was successfully integrated into care protocols. Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

Official Title
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Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

Conditions
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Acute Respiratory Distress Syndrome, COVID-19

Intervention / Treatment
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* Other: Prone decubitus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient with COVID-19 pneumonia according to the diagnostic criteria in effect at the time of inclusion or very highly suspected. Patient treated with nasal high-flow Mild, moderate or severe ARDS: bilateral radiological opacities not fully explained by effusions, atelectasis or nodules; acute hypoxemia with worsening within the previous 7 days, not fully explained by left ventricular failure; PaO2/FiO2 ratio < 300 mmHg (or equivalent SpO2/FiO2). Covered by or having the rights to French social security Informed Consent Exclusion Criteria: Pregnant or breastfeeding woman Indication for immediate tracheal intubation Progressive significant acute circulatory insufficiency Impaired alertness, confusion, restlessness Body mass index > 40 kg/m2 Thoracic trauma or other contraindication to prone position Pneumothorax with single anterior thoracic drain and persistent bubbling Vulnerable person: safeguard of justice, guardianship or authorship known at inclusion

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prone decubitus group<br>Prone positioning of patients on nasal high-flow oxygen therapy with usual care | Other: Prone decubitus<br>* According to the tolerance, the objective is to spend as much time as possible, up to 16 hours and beyond in prone position every 24 hours. At least two sessions of at least 30 minutes each must be performed daily.<br>|
| No Intervention: Control group<br>Patients on nasal high-flow oxygen therapy with usual care and positioned in supine | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic failure within 14 days of randomization | Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels. | From randomization to day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic failure within 28 days of randomization | Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels. | From randomization to day 28 | 
| Timeframe of intubation or death |  | From randomization to day 28 | 
| Timeframe of therapeutic escalation (in case of non-invasive ventilation at two pressure levels) |  | From randomization to day 28 | 
| Evolution of oxygenation (PaO2/FiO2 ratio or SpO2/FiO2 surrogate) over the 14 days following randomization |  | From randomization to day 14 | 
| Evolution of the SpO2/FiO2 ratio during the first prone session |  | From randomization to day 1 | 
| Evolution of the ROX index during the first prone session | ROX index is the ratio of pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate. | From randomization to day 1 | 
| Evolution of the World Health Organization disease severity score of COVID | Score reaches from 1 to 7, 7 indicates worse outcome | From randomization to day 28 | 
| Patient comfort before, during and after the first prone position session | Comfort evaluted by the patient through a visual analogical scale | From randomization to day 1 | 
| Occurrence of skin lesions on the anterior surface of the body |  | From randomization to day 28 | 
| Displacement of invasive devices during reversals | Invasive devices include : central and peripheric vascular catheters, tracheal tube, urinary catheter, chest tubes. | From randomization to day 28 | 
| Days of nasal High-Flow therapy use in the general population, in non-intubated patients and in intubated patients |  | From randomization to day 28 | 
| Days spent in the intensive care unit and in the hospital |  | From randomization to day 28 | 
| Mortality in the intensive care unit and in the hospital |  | From randomization to day 28 | 
| Ventilator-free-days within 28 days of randomization |  | From randomization to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, COVID-19, SARS-CoV-2, Nasal High-Flow, Prone position