APPROVE-CARE: Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE

• Sponsor: University College Hospital Galway (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04347941
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.5
• Patients Per Site Per Month: 3.7

Study Details

Study Description

Brief Summary

Prone positioning (PP) is an effective first-line intervention to treat moderate-severe acute respiratory distress syndrome (ARDS) patients receiving invasive mechanical ventilation, as it improves gas exchanges and lowers mortality.The use of PP in awake self-ventilating patients with (e.g. COVID-19 induced) ARDS could improve gas exchange and reduce the need for invasive mechanical ventilation, but has not been studied outside of case series.The investigators will conduct a randomized controlled study of patients with COVID-19 induced respiratory failure to determine if prone positioning reduces the need for mechanical ventilation compared to standard management.

Condition or Disease	Intervention/Treatment	Phase
ARDS, Human; Mechanical Ventilation Complication; COVID19	Procedure: Prone Positioning; Procedure: Standard of care.	N/A

Detailed Description

Prone positioning (PP) is an adjunctive therapy used that has been proven to save lives in sedated patients with confirmed moderate-severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation (MV). PP involves placing patients in the prone, i.e. face down position for time periods of up to 16 hours per day. PP promotes lung homogeneity, improves gas exchange and respiratory mechanics permitting reduction of ventilation intensity, and reducing ventilator-induced lung injury (VILI).

Maintaining self-ventilation is associated with increased aeration of dependent lung regions, less need for sedation, improved cardiac filling and removes the risk of VILI, and so is an important therapeutic goal in hypoxic patients. The use of PP in awake self-ventilating patients with COVID-19 induced acute hypoxic respiratory failure (AHRF) and/or ARDS could improve gas exchange and reduce the need for invasive MV, but has not been studied outside of case series.

However, an increase in oxygenation does not necessarily reduce the risk of invasive MV. PP has significant attached risks such as causing pressure sores in patients, PP is uncomfortable for some patients, it increases nursing workload, and if ineffective could hinder the delivery of other (effective) medical care. Hence there is a need to determine if PP of awake patients is effective in reducing the need for invasive MV. This multi-centre, open label, randomized controlled study of COVID-19 induced AHRF/ARDS will determine if PP reduces the need for mechanical ventilation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE
• Actual Study Start Date: Jul 11, 2020
• Actual Primary Completion Date: Jan 26, 2021
• Actual Study Completion Date: Jan 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prone Positioning Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals	Procedure: Prone Positioning; Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula
Active Comparator: Standard Care Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded.	Procedure: Standard of care.; Standard of care. Prone positioning may be administered as a rescue therapy

Outcome Measures

Primary Outcome Measures

1. The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. [Up to 28 days post randomisation]

   A measure of effect of awake prone positioning in patients with confirmed or suspected COVID-19 acute hypoxemic respiratory failure undergoing supplemental oxygen via high flow nasal cannular oxygen on reducing requirement for invasive mechanical ventilation or death. Outcome measure is calculated as a count of the number of patients who went onto require invasive mechanical ventilation or died up to 28 days post randomization.

Secondary Outcome Measures

1. Length of Time Tolerating Prone Positioning [Daily during intervention up to 14 days post randomisation]

   description of duration of prone positioning in hours per day from day 0 to day 14 in trial

2. PaO2/FiO2 Ratio Measured Before Prone Positioning [Immediately before intervention]

   Measure of change in oxygenation before intervention in the patients assigned to awake prone positioning

3. PaO2/FiO2 Ratio After 1 Hours of Prone Positioning [During intervention]

   Measure of change in oxygenation following patients being placed in the prone position for 1 hour

4. SpO2/FiO2 Ratio Measured Before Prone Positioning [Immediately before intervention]

   Measure of oxygenation using pulse oximetry before intervention where ABG not available

5. SpO2/FiO2 Ratio After 1 Hour in Prone Positioning [During Intervention]

   Measure of oxygenation 1 hour after intervention where ABG not available

6. Number Requiring Increase in Ventilatory Assistance [Up to 28 days post randomisation]

   Number of patients in each group requiring an increase in the respiratory support from baseline high flow nasal cannula oxygen post randomization up to 28 days later, defined as need for continuous positive airway pressure (CPAP), bilevel positive airway pressure (biPAP)

7. Work of Breathing Assessment (Respiratory Distress Scale) [Immediately before and during intervention]

   Measure of work of breathing in COVID-19 based on Oxygen Delivery Device, Oxygen Saturation and respiratory rate and accessory muscle use with 0-3 Mild, 4-6 Moderate and 7-10 Severe

8. Changes in Bioimpedance Measures of Lung Edema in Patients in PP [During intervention]

   Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning

9. Use of Awake Prone Positioning as a Rescue Intervention in Control Patients [Up to 28 days post randomisation]

   Number of patients who underwent rescue awake prone positioning in control patients by physicians in response to hypoxia

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Suspected or confirmed COVID19 infection

• Bilateral Infiltrates on CXR

• SpO2 <94% on FiO2 40% by either venturi facemask or high flow nasal cannula

• RR <40

• Written informed consent

Exclusion Criteria:

• Age <18

• Uncooperative or likely to be unable to lie on abdomen for 16 hours

• Receiving comfort care only

• Multi-organ failure

• RR>40

• Contraindication to PP (e.g. vomiting, abdominal wound, unstable pelvic/spinal lesions, pregnancy >20/40 gestation, severe brain injury).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Galway University Hospital	Galway		Ireland

Sponsors and Collaborators

• University College Hospital Galway

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 1, 2020

More Information

Additional Information:

• Result of Meta-trial in which RCT was incorporated

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.

• Responsible Party: John Laffey, Professor, Anaesthesia and Intensive Care Medicine, School of Medicine, NUI Galway, University College Hospital Galway
• ClinicalTrials.gov Identifier: NCT04347941
• Other Study ID Numbers: APPROVE-CARE-2020
• First Posted: Apr 15, 2020
• Last Update Posted: Dec 2, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Respiratory Insufficiency; Respiratory Distress Syndrome

Study Results

Participant Flow

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Prone Positioning	Standard Care	Total
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 58.3%	7 58.3%	14 58.3%
>=65 years	5 41.7%	5 41.7%	10 41.7%
Sex: Female, Male (Count of Participants)
Female	3 25%	5 41.7%	8 33.3%
Male	9 75%	7 58.3%	16 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	12 100%	12 100%	24 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Ireland	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure.
Description	A measure of effect of awake prone positioning in patients with confirmed or suspected COVID-19 acute hypoxemic respiratory failure undergoing supplemental oxygen via high flow nasal cannular oxygen on reducing requirement for invasive mechanical ventilation or death. Outcome measure is calculated as a count of the number of patients who went onto require invasive mechanical ventilation or died up to 28 days post randomization.
Time Frame	Up to 28 days post randomisation

Outcome Measure Data

Analysis Population Description

Number of patients who required invasive mechanical ventilation or who died in each group up to 28 days post randomization.

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	12	12
Count of Participants [Participants]	0 0%	2 16.7%

2. Secondary Outcome

Title	Length of Time Tolerating Prone Positioning
Description	description of duration of prone positioning in hours per day from day 0 to day 14 in trial
Time Frame	Daily during intervention up to 14 days post randomisation

Outcome Measure Data

Analysis Population Description

description of duration of prone positioning in hours per day from day 0 to day 14 in trial

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	12	12
Mean (Standard Deviation) [hours]	3.3 (2.7)	1.0 (2.5)

3. Secondary Outcome

Title	PaO2/FiO2 Ratio Measured Before Prone Positioning
Description	Measure of change in oxygenation before intervention in the patients assigned to awake prone positioning
Time Frame	Immediately before intervention

Outcome Measure Data

Analysis Population Description

paO2 to fiO2 ratio before prone positioning in the group assigned to undergo awake prone positioning

Arm/Group Title	Prone Positioning	Standard of Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Patients with suspected or confirmed COVID-19 pneumonia who are randomized to not undergo awake prone positioning but receive otherwise identical care as the awake prone positioning group.
Measure Participants	12	12
Mean (Standard Deviation) [ratio]	144 (52)	114 (40)

4. Secondary Outcome

Title	PaO2/FiO2 Ratio After 1 Hours of Prone Positioning
Description	Measure of change in oxygenation following patients being placed in the prone position for 1 hour
Time Frame	During intervention

Outcome Measure Data

Analysis Population Description

change in paO2 one hour after proning in the individuals who were in the intervention group and underwent awake prone positioning

Arm/Group Title	Prone Positioning
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula
Measure Participants	12
Mean (Standard Deviation) [ratio]	33 (32)

5. Secondary Outcome

Title	SpO2/FiO2 Ratio Measured Before Prone Positioning
Description	Measure of oxygenation using pulse oximetry before intervention where ABG not available
Time Frame	Immediately before intervention

Outcome Measure Data

Analysis Population Description

spO2 to fiO2 ratio at baseline prior to awake prone position in those undergoing awake prone position, and on the morning post enrolment for patients undergoing standard of care treatment

Arm/Group Title	Prone Positioning	Standard of Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Patients with suspected or confirmed COVID-19 pneumonia requiring high flow nasal cannula oxygen who were randomized to not undergo awake prone positioning as part of their management and received otherwise identical treatment as the awake prone positioning arm.
Measure Participants	12	12
Mean (Standard Deviation) [ratio]	193 (45)	178 (52)

6. Secondary Outcome

Title	SpO2/FiO2 Ratio After 1 Hour in Prone Positioning
Description	Measure of oxygenation 1 hour after intervention where ABG not available
Time Frame	During Intervention

Outcome Measure Data

Analysis Population Description

spO2 to fiO2 ratio following 1 hour in prone position

Arm/Group Title	Prone Positioning
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula
Measure Participants	12
Mean (Standard Deviation) [ratio]	247 (53)

7. Secondary Outcome

Title	Number Requiring Increase in Ventilatory Assistance
Description	Number of patients in each group requiring an increase in the respiratory support from baseline high flow nasal cannula oxygen post randomization up to 28 days later, defined as need for continuous positive airway pressure (CPAP), bilevel positive airway pressure (biPAP)
Time Frame	Up to 28 days post randomisation

Outcome Measure Data

Analysis Population Description

Number of patients in each group requiring an increase in the respiratory support from baseline high flow nasal cannula oxygen post randomization up to 28 days later, defined as need for continuous positive airway pressure (CPAP), bilevel positive airway pressure (biPAP)

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	12	12
Count of Participants [Participants]	4 33.3%	4 33.3%

8. Secondary Outcome

Title	Work of Breathing Assessment (Respiratory Distress Scale)
Description	Measure of work of breathing in COVID-19 based on Oxygen Delivery Device, Oxygen Saturation and respiratory rate and accessory muscle use with 0-3 Mild, 4-6 Moderate and 7-10 Severe
Time Frame	Immediately before and during intervention

Outcome Measure Data

Analysis Population Description

We did not carry out this aspect of the study due to constraints related to the Pandemic

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	0	0

9. Secondary Outcome

Title	Changes in Bioimpedance Measures of Lung Edema in Patients in PP
Description	Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning
Time Frame	During intervention

Outcome Measure Data

Analysis Population Description

Due to constraints related to the pandemic, this aspect of the study was not carried out.

Arm/Group Title	Prone Positioning	Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	0	0

10. Secondary Outcome

Title	Use of Awake Prone Positioning as a Rescue Intervention in Control Patients
Description	Number of patients who underwent rescue awake prone positioning in control patients by physicians in response to hypoxia
Time Frame	Up to 28 days post randomisation

Outcome Measure Data

Analysis Population Description

Number of patients who underwent awake prone positioning in the control arm of the study as a rescue manoeuvre in response to hypoxia.

Arm/Group Title	Standard Care
Arm/Group Description	Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
Measure Participants	12
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	hospital discharge or 28 days
Arm/Group Title	Prone Positioning		Standard Care
Arm/Group Description	Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals Prone Positioning: Patient will be asked to remain for at least one hour and to a maximum total of 16 hours in prone position with 45 minutes breaks for meals. Immediately prior to proning, if spO2 <94% on FiO2 0.4, start on 100% O2 to ensure stability during proning. A nurse or assistant will assist patient to turn on side and then face down with the support of pillows as required for comfort, ensure that they are predominantly on their chest rather than on their side. Arms can be at side, in swimmer position and can be moved to patients' comfort, pillows under knees and chest for comfort and call bell to be at patient's arm's length. Vitals and work of breathing score will be measured before and at 1 hour into each proning session and at the end of each session. Total length of time in prone position will be recorded. Intervention to continue daily until oxygen requirement to maintain spO2 >94% is below FiO2 0.4 via venturi facemask or high flow nasal cannula		Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. Standard of care.: Standard of care. Prone positioning may be administered as a rescue therapy
All Cause Mortality
	Prone Positioning		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Prone Positioning		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Prone Positioning		Standard Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

Study was terminated after an interim analysis of a prospective meta-trial in which the patients reached statistical criteria for efficiency

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.