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

• ClinicalTrials.gov Identifier: NCT04347941
• Recruitment Status: Terminated
• First Posted: April 15, 2020
• Results First Posted: December 2, 2021
• Last Update Posted: December 2, 2021
• Sponsor: University College Hospital Galway
• Information provided by (Responsible Party): John Laffey, University College Hospital Galway

Tracking Information

• First Submitted Date: April 8, 2020
• First Posted Date: April 15, 2020
• Results First Submitted Date: November 20, 2021
• Results First Posted Date: December 2, 2021
• Last Update Posted Date: December 2, 2021
• Actual Study Start Date: July 11, 2020
• Actual Primary Completion Date: January 26, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2021)

The Effect of Prone Positioning on Requirement for Invasive Mechanical Ventilation or Death in Patients With COVID 19 Induced Respiratory Failure. [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 14, 2020)

The effect of prone positioning on requirement for invasive mechanical ventilation in patients with COVID 19 induced respiratory failure. [ Time Frame: Up to 28 days post randomisation ]

A measure of effect of awake prone positioning in reducing requirement for invasive mechanical ventilation.

Current Secondary Outcome Measures (submitted: November 30, 2021)

• Length of Time Tolerating Prone Positioning [ Time Frame: 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
• PaO2/FiO2 Ratio Measured Before Prone Positioning [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Immediately before intervention ]
  Measure of oxygenation using pulse oximetry before intervention where ABG not available
• SpO2/FiO2 Ratio After 1 Hour in Prone Positioning [ Time Frame: During Intervention ]
  Measure of oxygenation 1 hour after intervention where ABG not available
• Number Requiring Increase in Ventilatory Assistance [ Time Frame: 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)
• Work of Breathing Assessment (Respiratory Distress Scale) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 28 days post randomisation ]
  Number of patients who underwent rescue awake prone positioning in control patients by physicians in response to hypoxia

Original Secondary Outcome Measures (submitted: April 14, 2020)

• Length of time tolerating prone positioning [ Time Frame: Daily during intervention up to 28 days post randomisation ]
  Total time spent in prone and supine position as recorded by nurse
• PaO2/FiO2 measured before prone positioning [ Time Frame: Immediately before intervention ]
  Measure of change in oxygenation before intervention
• PaO2/FiO2 ratio after 1 hours of prone positioning [ Time Frame: During intervention ]
  Measure of change in oxygenation following intervention
• SpO2/FiO2 ratio measured before prone positioning [ Time Frame: Immediately before intervention ]
  Measure of change in oxygenation using pulse oximetry before intervention where ABG not available
• SpO2/FiO2 ratio after 1 hours of prone positioning [ Time Frame: During Intervention ]
  Measure of change in oxygenation before intervention where ABG not available
• Number requiring increase in ventilatory assistance (CPAP+BIPAP+IMV etc) [ Time Frame: Up to 28 days post randomisation ]
  Escalation of ventilatory support
• Work of breathing assessment (Respiratory distress scale) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 28 days post randomisation ]
  Rescue awake prone positioning in control patients in response to hypoxia

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

Descriptive Information

• Brief Title: Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE
• Official Title: Awake Prone Positioning to Reduce Invasive VEntilation in COVID-19 Induced Acute Respiratory failurE
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• ARDS, Human
• Mechanical Ventilation Complication
• COVID19

Intervention

• 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
• Procedure: Standard of care.
  Standard of care. Prone positioning may be administered as a rescue therapy

Study Arms

• Experimental: Prone Positioning
  Intervention patients will remain up to 16 hours per day in Prone Positioning with 45 minutes breaks for meals
  Intervention: Procedure: Prone Positioning
• Active Comparator: Standard Care
  Control patients will receive full standard care. Prone Positioning as a rescue intervention is permitted and is recorded.
  Intervention: Procedure: Standard of care.

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.
• 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: Terminated
• Actual Enrollment (submitted: November 30, 2021): 24
• Original Estimated Enrollment (submitted: April 14, 2020): 200
• Actual Study Completion Date: January 26, 2021
• Actual Primary Completion Date: January 26, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Ireland

Administrative Information

• NCT Number: NCT04347941
• Other Study ID Numbers: APPROVE-CARE-2020
• 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: Electronic Case report form following informed consent, all patient identification removed, and individual patient response to intervention will be shared.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: up to 15 years post study

• Current Responsible Party: John Laffey, University College Hospital Galway
• Original Responsible Party: Same as current
• Current Study Sponsor: University College Hospital Galway
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University College Hospital Galway
• Verification Date: November 2021