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

• ClinicalTrials.gov Identifier: NCT04358939
• Recruitment Status: Recruiting
• First Posted: April 24, 2020
• Last Update Posted: January 11, 2021
• Sponsor: University Hospital, Tours
• Information provided by (Responsible Party): University Hospital, Tours

Tracking Information

• First Submitted Date: April 16, 2020
• First Posted Date: April 24, 2020
• Last Update Posted Date: January 11, 2021
• Actual Study Start Date: April 27, 2020
• Estimated Primary Completion Date: November 10, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2020)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 4, 2020)

• Therapeutic failure within 28 days of randomization [ Time Frame: From randomization to day 28 ]
  Therapeutic failure is defined by death or intubation or use of non-invasive ventilation at two pressure levels.
• 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 ]
  ROX index is the ratio of pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate.
• Evolution of the World Health Organization disease severity score of COVID [ Time Frame: From randomization to day 28 ]
  Score reaches from 1 to 7, 7 indicates worse outcome
• Patient comfort before, during and after the first prone position session [ Time Frame: From randomization to day 1 ]
  Comfort evaluted by the patient through a visual analogical scale
• 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 ]
  Invasive devices include : central and peripheric vascular catheters, tracheal tube, urinary catheter, chest tubes.
• 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 ]

Original Secondary Outcome Measures (submitted: April 20, 2020)

• 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 ]
  ROX index is the ratio of pulse oximetry (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate.
• Evolution of the World Health Organization disease severity score of COVID [ Time Frame: From randomization to day 28 ]
  Score reaches from 1 to 7, 7 indicates worse outcome
• Patient comfort before, during and after the first prone position session [ Time Frame: From randomization to day 1 ]
  Comfort evaluted by the patient through a visual analogical scale
• 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 ]
  Invasive devices include : central and peripheric vascular catheters, tracheal tube, urinary catheter, chest tubes.
• Days of nasal High-Flow therapy use [ 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prone Position in Patients on High-flow Nasal Oxygen Therapy for COVID-19 (HIGH-PRONE-COVID-19)
• Official Title: Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

Brief 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 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Respiratory Distress Syndrome
• COVID-19

Intervention

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.

Study Arms

• Experimental: Prone decubitus group
  Prone positioning of patients on nasal high-flow oxygen therapy with usual care
  Intervention: Other: Prone decubitus
• No Intervention: Control group
  Patients on nasal high-flow oxygen therapy with usual care and positioned in supine

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 12, 2020): 404
• Original Estimated Enrollment (submitted: April 20, 2020): 248
• Estimated Study Completion Date: November 24, 2021
• Estimated Primary Completion Date: November 10, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Yonatan PEREZ, MD; (0)2.47.47.98.51 ext +33; yonatperez@gmail.com

Contact: Stephan EHRMANN, MD-PhD; (0)2.47.47.98.51 ext +33; stephan.ehrmann@univ-tours.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04358939
• Other Study ID Numbers: HIGH-PRONE-COVID-19; 2020-A01121-38 ( Other Identifier: IdRCB ); DR200125 ( Other Identifier: University Hospital, Tours )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data after de-identification can be obtained by contacting the corresponding author.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data will be available immediately following publication and ending in 5 years.
• Access Criteria: Contact with the corresponding author.

• Responsible Party: University Hospital, Tours
• Study Sponsor: University Hospital, Tours
• Collaborators: Not Provided

Investigators

• Study Director: Yonatan PEREZ, MD; No affiliation

• PRS Account: University Hospital, Tours
• Verification Date: January 2021