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Enrollment for trial was terminated on January 26, 2021 after a third interim analysis demonstrated that a pre-defined statistical criteria for efficacy were met as part of meta-trial study of awake prone positioning.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prone Positioning | Experimental | Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals |
|
| Standard Care | Active Comparator | Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prone Positioning | Procedure | 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 | Description | Time Frame |
|---|---|---|
| The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. | 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. | Up to 28 days post randomisation |
| Measure | Description | Time Frame |
|---|---|---|
| Length of Time Tolerating Prone Positioning | description of duration of prone positioning in hours per day from day 0 to day 14 in trial | Daily during intervention up to 14 days post randomisation |
| PaO2/FiO2 Ratio Measured Before Prone Positioning |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Galway University Hospital | Galway | Ireland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34425070 | Background | 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. | |
| 33177145 |
| Label | URL |
|---|---|
| Result of Meta-trial in which RCT was incorporated | View source |
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Electronic Case report form following informed consent, all patient identification removed, and individual patient response to intervention will be shared.
up to 15 years post study
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| ID | Title | Description |
|---|---|---|
| FG000 | Prone Positioning | 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 |
| FG001 | Standard Care | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients with suspected or confirmed COVID-19 pneumonia requiring high flow nasal cannula oxygen were randomized to either awake prone positioning or standard of care. The primary outcome was the requirement for invasive mechanical or death post 28 days randomization.
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| ID | Title | Description |
|---|---|---|
| BG000 | Prone Positioning | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. | 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. | Number of patients who required invasive mechanical ventilation or who died in each group up to 28 days post randomization. | Posted | Count of Participants | Participants | Up to 28 days post randomisation |
|
hospital discharge or 28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prone Positioning | 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 |
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Study was terminated after an interim analysis of a prospective meta-trial in which the patients reached statistical criteria for efficiency
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Bairbre McNicholas | National University of Ireland, Galway | +35391893063 | bmcnicholas@nuigalway.ie |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 1, 2020 | Nov 28, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D011024 | Pneumonia, Viral |
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| ID | Term |
|---|---|
| D016684 | Prone Position |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D011187 | Posture |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
| D019984 | Quality Indicators, Health Care |
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|
| Standard of care. | Procedure | Standard of care. Prone positioning may be administered as a rescue therapy |
|
Measure of change in oxygenation before intervention in the patients assigned to awake prone positioning
| Immediately before intervention |
| PaO2/FiO2 Ratio After 1 Hours of Prone Positioning | Measure of change in oxygenation following patients being placed in the prone position for 1 hour | During intervention |
| SpO2/FiO2 Ratio Measured Before Prone Positioning | Measure of oxygenation using pulse oximetry before intervention where ABG not available | Immediately before intervention |
| SpO2/FiO2 Ratio After 1 Hour in Prone Positioning | Measure of oxygenation 1 hour after intervention where ABG not available | During Intervention |
| Number Requiring Increase in Ventilatory Assistance | 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) | Up to 28 days post randomisation |
| Work of Breathing Assessment (Respiratory Distress Scale) | 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 | Immediately before and during intervention |
| Changes in Bioimpedance Measures of Lung Edema in Patients in PP | Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning | During intervention |
| Use of Awake Prone Positioning as a Rescue Intervention in Control Patients | Number of patients who underwent rescue awake prone positioning in control patients by physicians in response to hypoxia | Up to 28 days post randomisation |
| Result |
| 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. |
| BG001 | Standard Care | 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Standard Care | 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 |
|
|
| Secondary | Length of Time Tolerating Prone Positioning | description of duration of prone positioning in hours per day from day 0 to day 14 in trial | description of duration of prone positioning in hours per day from day 0 to day 14 in trial | Posted | Mean | Standard Deviation | hours | Daily during intervention up to 14 days post randomisation |
|
|
|
| Secondary | PaO2/FiO2 Ratio Measured Before Prone Positioning | Measure of change in oxygenation before intervention in the patients assigned to awake prone positioning | paO2 to fiO2 ratio before prone positioning in the group assigned to undergo awake prone positioning | Posted | Mean | Standard Deviation | ratio | Immediately before intervention |
|
|
|
| Secondary | PaO2/FiO2 Ratio After 1 Hours of Prone Positioning | Measure of change in oxygenation following patients being placed in the prone position for 1 hour | change in paO2 one hour after proning in the individuals who were in the intervention group and underwent awake prone positioning | Posted | Mean | Standard Deviation | ratio | During intervention |
|
|
|
| Secondary | SpO2/FiO2 Ratio Measured Before Prone Positioning | Measure of oxygenation using pulse oximetry before intervention where ABG not available | 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 | Posted | Mean | Standard Deviation | ratio | Immediately before intervention |
|
|
|
| Secondary | SpO2/FiO2 Ratio After 1 Hour in Prone Positioning | Measure of oxygenation 1 hour after intervention where ABG not available | spO2 to fiO2 ratio following 1 hour in prone position | Posted | Mean | Standard Deviation | ratio | During Intervention |
|
|
|
| Secondary | Number Requiring Increase in Ventilatory Assistance | 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) | 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) | Posted | Count of Participants | Participants | Up to 28 days post randomisation |
|
|
|
| Secondary | Work of Breathing Assessment (Respiratory Distress Scale) | 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 | We did not carry out this aspect of the study due to constraints related to the Pandemic | Posted | Immediately before and during intervention |
|
|
| Secondary | Changes in Bioimpedance Measures of Lung Edema in Patients in PP | Substudy examining use of bioimpedance as a surrogate measure of lung edema following prone positioning | Due to constraints related to the pandemic, this aspect of the study was not carried out. | Posted | During intervention |
|
|
| Secondary | Use of Awake Prone Positioning as a Rescue Intervention in Control Patients | Number of patients who underwent rescue awake prone positioning in control patients by physicians in response to hypoxia | Number of patients who underwent awake prone positioning in the control arm of the study as a rescue manoeuvre in response to hypoxia. | Posted | Count of Participants | Participants | Up to 28 days post randomisation |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Standard Care | 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 | 0 | 12 | 0 | 12 | 0 | 12 |
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| D011014 |
| Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |