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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Prone decubitus

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 405
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Aix-en-Provence, France, 13616
    • Intensive Care Unit, University Hospital, Aix
  • Amiens, France, 80054
    • Medical Intensive Care Unit, University Hospital, Amiens
  • Argenteuil, France, 95100
    • Intensive Care Unit, Hospital, Argenteuil
  • Blois, France, 41016
    • Intensive Care Unit, Hospital,
  • Brest, France, 29609
    • Medical Intensive Care Unit, University Hospital, Brest
  • Béthune, France, 62408
    • Medical Intensive Care Unit, Hospital, Béthune
  • Caen, France, 14033
    • Medical Intensive Care Unit, University Hospital, Caen
  • Colombes, France, 92700
    • Intensive Care Unit, Louis Mourier-APHP
  • Dax, France, 40107
    • Intensive Care Unit, Hospital, Dax
  • Dijon, France, 21033
    • Medical Intensive Care Unit, University Hospital, Dijon
  • Grenoble, France
    • Medical Intensive Care Unit, University Hospital, Grenoble
  • La Roche-sur-Yon, France, 85925
    • Intensive Care Unit, Hospital, La Roche-sur-Yon
  • Le Mans, France, 72037
    • Intensive Care Unit, Hospital, Le Mans
  • Lille, France, 59037
    • Intensive Care Unit, University Hospital, Lille
  • Nantes, France, 44093
    • Medical Intensive Care Unit, University Hospital, Nantes
  • Nice, France, 06202
    • Medical Intensive Care Unit, University Hospital, Nice
  • Orléans, France, 45067
    • Medical Intensive Care Unit, Hospital, Orléans
  • Paris, France, 75020
    • Medical Intensive Care Unit, Tenon-APHP
  • Poitiers, France, 86021
    • Medical Intensive Care Unit, University Hospital, Poitiers
  • Tours, France, 37044
    • Medical Intensive Care Unit, University Hospital, Tours
  • Tours, France, 37170
    • Surgical Intensive Care Unit, University Hospital, Tours
  • Valence, France, 26953
    • Intensive Care Unit, Hospital, Valence
  • Vandœuvre-lès-Nancy, France, 54511
    • Medical Intensive Care Unit, University Hospital, Nancy
  • Vannes, France, 56017
    • Intensive Care Unit, Hospital, Vannes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prone decubitus group; Prone positioning of patients on nasal high-flow oxygen therapy with usual care	Other: Prone decubitus; 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.
No Intervention: Control group; Patients on nasal high-flow oxygen therapy with usual care and positioned in supine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Yonatan PEREZ, MD, No Affiliation

Publications and helpful links

General Publications

• Ehrmann S, Li J, Ibarra-Estrada M, Perez Y, Pavlov I, McNicholas B, Roca O, Mirza S, Vines D, Garcia-Salcido R, Aguirre-Avalos G, Trump MW, Nay MA, Dellamonica J, Nseir S, Mogri I, Cosgrave D, Jayaraman D, Masclans JR, Laffey JG, Tavernier E; Awake Prone Positioning Meta-Trial Group. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021 Dec;9(12):1387-1395. doi: 10.1016/S2213-2600(21)00356-8. Epub 2021 Aug 20.
• Tavernier E, McNicholas B, Pavlov I, Roca O, Perez Y, Laffey J, Mirza S, Cosgrave D, Vines D, Frat JP, Ehrmann S, Li J. Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial. BMJ Open. 2020 Nov 11;10(11):e041520. doi: 10.1136/bmjopen-2020-041520.
• Ibarra-Estrada M, Li J, Laffey JG, Pavlov I, Roca O, Perez Y, McNicholas B, Vines D, Tavernier E, Ehrmann S. Prone positioning might reduce the need for intubation in people with severe COVID-19 - Authors' reply. Lancet Respir Med. 2021 Dec;9(12):e111. doi: 10.1016/S2213-2600(21)00449-5. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): February 21, 2021
• Study Completion (Actual): February 21, 2021

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Estimated): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Acute Respiratory Distress Syndrome; Nasal High-Flow; Prone position
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Respiratory Distress Syndrome
• Other Study ID Numbers: HIGH-PRONE-COVID-19; 2020-A01121-38 (Other Identifier: IdRCB); DR200125 (Other Identifier: University Hospital, Tours)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data after de-identification can be obtained by contacting the corresponding author.
• IPD Sharing Time Frame: Data will be available immediately following publication and ending in 5 years.
• IPD Sharing Access Criteria: Contact with the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No