Acute Respiratory Distress SyndromeNCT04358939
Prone Position in Patients on High-flow Nasal Oxygen Therapy for COVID-19 (HIGH-PRONE-COVID-19)
A study testing Prone decubitus in people with Acute Respiratory Distress Syndrome and COVID-19, run by University Hospital, Tours at 24 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome, COVID-19
- What is being tested?
- Prone decubitus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 405 participants
- Where
- 24 sitesFrance
- Study dates
- 27 Apr 2020to 21 Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
France24 sites
Intensive Care Unit, University Hospital, Aix
Aix-en-Provence, 13616
Medical Intensive Care Unit, University Hospital, Amiens
Amiens, 80054
Intensive Care Unit, Hospital, Argenteuil
Argenteuil, 95100
Medical Intensive Care Unit, Hospital, Béthune
Béthune, 62408
Intensive Care Unit, Hospital,
Blois, 41016
Medical Intensive Care Unit, University Hospital, Brest
Brest, 29609
Medical Intensive Care Unit, University Hospital, Caen
Caen, 14033
Intensive Care Unit, Louis Mourier-APHP
Colombes, 92700
Intensive Care Unit, Hospital, Dax
Dax, 40107
Medical Intensive Care Unit, University Hospital, Dijon
Dijon, 21033
Medical Intensive Care Unit, University Hospital, Grenoble
Grenoble
Intensive Care Unit, Hospital, La Roche-sur-Yon
La Roche-sur-Yon, 85925
Intensive Care Unit, Hospital, Le Mans
Le Mans, 72037
Intensive Care Unit, University Hospital, Lille
Lille, 59037
Medical Intensive Care Unit, University Hospital, Nantes
Nantes, 44093
Medical Intensive Care Unit, University Hospital, Nice
Nice, 06202
Medical Intensive Care Unit, Hospital, Orléans
Orléans, 45067
Medical Intensive Care Unit, Tenon-APHP
Paris, 75020
Medical Intensive Care Unit, University Hospital, Poitiers
Poitiers, 86021
Medical Intensive Care Unit, University Hospital, Tours
Tours, 37044
Surgical Intensive Care Unit, University Hospital, Tours
Tours, 37170
Intensive Care Unit, Hospital, Valence
Valence, 26953
Medical Intensive Care Unit, University Hospital, Nancy
Vandœuvre-lès-Nancy, 54511
Intensive Care Unit, Hospital, Vannes
Vannes, 56017
About this study
Official title: 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.
Read the 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.
- Conditions
- Acute Respiratory Distress Syndrome, COVID-19
- Being tested
- Prone decubitus
- Keywords
- Acute Respiratory Distress Syndrome, COVID-19, SARS-CoV-2, Nasal High-Flow, Prone position
- Medical subject headings
- Respiratory Distress Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prone decubitusOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Prone decubitus group | Experimental | Prone positioning of patients on nasal high-flow oxygen therapy with usual care Receives: Other: Prone decubitus |
| Control group | No intervention | Patients on nasal high-flow oxygen therapy with usual care and positioned in supine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization to day 14
Secondary outcomes (14)
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.
Measured: From randomization to day 28
Timeframe of intubation or death
Measured: From randomization to day 28
Timeframe of therapeutic escalation (in case of non-invasive ventilation at two pressure levels)
Measured: From randomization to day 28
Evolution of oxygenation (PaO2/FiO2 ratio or SpO2/FiO2 surrogate) over the 14 days following randomization
Measured: From randomization to day 14
Evolution of the SpO2/FiO2 ratio during the first prone session
Measured: 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.
Measured: 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
Measured: 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
Measured: From randomization to day 1
Occurrence of skin lesions on the anterior surface of the body
Measured: 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.
Measured: From randomization to day 28
Days of nasal High-Flow therapy use in the general population, in non-intubated patients and in intubated patients
Measured: From randomization to day 28
Days spent in the intensive care unit and in the hospital
Measured: From randomization to day 28
Mortality in the intensive care unit and in the hospital
Measured: From randomization to day 28
Ventilator-free-days within 28 days of randomization
Measured: From randomization to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start27 Apr 2020
- Primary completion21 Feb 2021
- Study completion21 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 405 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yonatan PEREZ, MD, Study director, No affiliation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358939
- Sponsor's protocol ID
- HIGH-PRONE-COVID-19
- Other IDs
- 2020-A01121-38, DR200125
- Status last verified
- Dec 2025
- First submitted
- 16 Apr 2020
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data after de-identification can be obtained by contacting the corresponding author.
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.
PubMed 34425070Ibarra-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.
PubMed 34861160Tavernier 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.
PubMed 33177145
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04358939
- Acronym / sponsor ID
- HIGH-PRONE-COVID-19
- Conditions
- Acute Respiratory Distress Syndrome, COVID-19
- Keywords
- Acute Respiratory Distress Syndrome, COVID-19, SARS-CoV-2, Nasal High-Flow, Prone position
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 405 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 27 Apr 2020 (actual)
- Primary completion
- 21 Feb 2021 (actual)
- Study completion
- 21 Feb 2021 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prone decubitus group | Experimental | Other: Prone decubitusProne positioning of patients on nasal high-flow oxygen therapy with usual care |
| Control group | No intervention | –Patients on nasal high-flow oxygen therapy with usual care and positioned in supine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- Pregnant or breastfeeding woman
- Indication for immediate tracheal intubation
- Progressive significant acute circulatory insufficiency
- Impaired alertness, confusion, restlessness
- Body mass index > 40 kg/m2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prone decubitusAccording 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. | Other | Prone decubitus group |
Primary outcome
Therapeutic failure within 14 days of randomization
Time frame: From randomization to day 14
Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.
14 secondary outcomes
Therapeutic failure within 28 days of randomization
Time frame: From randomization to day 28
Timeframe of intubation or death
Time frame: From randomization to day 28
Timeframe of therapeutic escalation (in case of non-invasive ventilation at two pressure levels)
Time frame: From randomization to day 28
Evolution of oxygenation (PaO2/FiO2 ratio or SpO2/FiO2 surrogate) over the 14 days following randomization
Time frame: From randomization to day 14
Evolution of the SpO2/FiO2 ratio during the first prone session
Time frame: From randomization to day 1
Evolution of the ROX index during the first prone session
Time frame: From randomization to day 1
Evolution of the World Health Organization disease severity score of COVID
Time frame: From randomization to day 28
Patient comfort before, during and after the first prone position session
Time frame: From randomization to day 1
Occurrence of skin lesions on the anterior surface of the body
Time frame: From randomization to day 28
Displacement of invasive devices during reversals
Time frame: From randomization to day 28
Days of nasal High-Flow therapy use in the general population, in non-intubated patients and in intubated patients
Time frame: From randomization to day 28
Days spent in the intensive care unit and in the hospital
Time frame: From randomization to day 28
Mortality in the intensive care unit and in the hospital
Time frame: From randomization to day 28
Ventilator-free-days within 28 days of randomization
Time frame: From randomization to day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Results publication: PubMed 34425070Ehrmann 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.
- Results publication: PubMed 34861160Ibarra-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.
- Results publication: PubMed 33177145Tavernier 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.
- Individual participant dataSharing planned: Yes. Individual participant data after de-identification can be obtained by contacting the corresponding author.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yonatan PEREZ, MD study director
No affiliation
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prone decubitus in people with Acute Respiratory Distress Syndrome and COVID-19, run by University Hospital, Tours at 24 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapeutic failure within 14 days of randomization (time frame: From randomization to day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04358939, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.