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

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.	Not Applicable

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 (Clinical Trial)
• 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: July 11, 2020
• Actual Primary Completion Date: January 26, 2021
• Actual Study Completion Date: January 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. [ 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.

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. SpO2/FiO2 Ratio Measured Before Prone Positioning [ Time Frame: 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 [ Time Frame: During Intervention ]
   Measure of oxygenation 1 hour after intervention where ABG not available
6. 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)
7. 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
8. 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
9. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

Ireland

Galway University Hospital

Galway, Ireland

Sponsors and Collaborators

University College Hospital Galway

  Study Documents (Full-Text)

Documents provided by John Laffey, University College Hospital Galway:

Study Protocol and Statistical Analysis Plan  [PDF] October 1, 2020

More Information

Additional Information:

Result of Meta-trial in which RCT was incorporated 

Publications of Results:

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.

Other 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: April 15, 2020
• Results First Posted: December 2, 2021
• Last Update Posted: December 2, 2021
• Last Verified: November 2021

Individual Participant Data (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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: up to 15 years post study

• 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; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders