ARDS, Human, COVID19, Mechanical Ventilation Complication
Conditions
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.
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.
Interventions
PROCEDUREProne 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
PROCEDUREStandard of care.
Standard of care. Prone positioning may be administered as a rescue therapy
Sponsors
University College Hospital Galway
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| SpO2/FiO2 Ratio Measured Before Prone Positioning | Immediately before intervention | Measure of oxygenation using pulse oximetry before intervention where ABG not available |
| SpO2/FiO2 Ratio After 1 Hour in Prone Positioning | During Intervention | Measure of oxygenation 1 hour after intervention where ABG not available |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
Countries
Ireland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 12 |
| 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 | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | Prone Positioning | Standard Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 5 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 12 Participants | 12 Participants |
| Region of Enrollment Ireland | 24 participants | 12 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 16 Participants | 9 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
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.
Time frame: Up to 28 days post randomisation
Population: Number of patients who required invasive mechanical ventilation or who died in each group up to 28 days post randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prone Positioning | The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. | 0 Participants |
| Standard Care | The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. | 2 Participants |
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
Time frame: During intervention
Population: Due to constraints related to the pandemic, this aspect of the study was not carried out.
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
Time frame: Daily during intervention up to 14 days post randomisation
Population: description of duration of prone positioning in hours per day from day 0 to day 14 in trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prone Positioning | Length of Time Tolerating Prone Positioning | 3.3 hours | Standard Deviation 2.7 |
| Standard Care | Length of Time Tolerating Prone Positioning | 1.0 hours | Standard Deviation 2.5 |
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)
Time frame: Up to 28 days post randomisation
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prone Positioning | Number Requiring Increase in Ventilatory Assistance | 4 Participants |
| Standard Care | Number Requiring Increase in Ventilatory Assistance | 4 Participants |
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
Time frame: During intervention
Population: change in paO2 one hour after proning in the individuals who were in the intervention group and underwent awake prone positioning
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prone Positioning | PaO2/FiO2 Ratio After 1 Hours of Prone Positioning | 33 ratio | Standard Deviation 32 |
Secondary
PaO2/FiO2 Ratio Measured Before Prone Positioning
Measure of change in oxygenation before intervention in the patients assigned to awake prone positioning
Time frame: Immediately before intervention
Population: paO2 to fiO2 ratio before prone positioning in the group assigned to undergo awake prone positioning
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prone Positioning | PaO2/FiO2 Ratio Measured Before Prone Positioning | 144 ratio | Standard Deviation 52 |
| Standard Care | PaO2/FiO2 Ratio Measured Before Prone Positioning | 114 ratio | Standard Deviation 40 |
Secondary
SpO2/FiO2 Ratio After 1 Hour in Prone Positioning
Measure of oxygenation 1 hour after intervention where ABG not available
Time frame: During Intervention
Population: spO2 to fiO2 ratio following 1 hour in prone position
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prone Positioning | SpO2/FiO2 Ratio After 1 Hour in Prone Positioning | 247 ratio | Standard Deviation 53 |
Secondary
SpO2/FiO2 Ratio Measured Before Prone Positioning
Measure of oxygenation using pulse oximetry before intervention where ABG not available
Time frame: Immediately before intervention
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prone Positioning | SpO2/FiO2 Ratio Measured Before Prone Positioning | 193 ratio | Standard Deviation 45 |
| Standard Care | SpO2/FiO2 Ratio Measured Before Prone Positioning | 178 ratio | Standard Deviation 52 |
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
Time frame: Up to 28 days post randomisation
Population: Number of patients who underwent awake prone positioning in the control arm of the study as a rescue manoeuvre in response to hypoxia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prone Positioning | Use of Awake Prone Positioning as a Rescue Intervention in Control Patients | 0 Participants |
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
Time frame: Immediately before and during intervention
Population: We did not carry out this aspect of the study due to constraints related to the Pandemic