Prone Positioning for Patients on General Medical Wards With COVID19 (COVID-PRONE)

• ClinicalTrials.gov Identifier: NCT04383613
• Recruitment Status: Unknown
• First Posted: May 12, 2020
• Last Update Posted: May 13, 2021
• Sponsor: Unity Health Toronto
• Collaborators: Sunnybrook Health Sciences Centre; Sinai Health System; Toronto General Hospital; University Health Network, Toronto; William Osler Health System
• Information provided by (Responsible Party): Unity Health Toronto

Tracking Information

• First Submitted Date: May 5, 2020
• First Posted Date: May 12, 2020
• Last Update Posted Date: May 13, 2021
• Actual Study Start Date: May 15, 2020
• Estimated Primary Completion Date: June 1, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 8, 2020): Composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more [ Time Frame: From date of randomization until the date of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, need for FiO2 of 60% or more, or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 5, 2021)

• Length of hospitalization [ Time Frame: Up to 4 weeks [or until hospital discharge] ]
• Adverse events of prone positioning (i.e., venous thromboembolism, pneumonia) [ Time Frame: Up to 7 days [or until hospital discharge] ]
• In-hospital all-cause mortality [ Time Frame: From date of randomization until the date of in-hospital all-cause mortality or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Invasive or non-invasive mechanical ventilation [ Time Frame: From date of randomization until the date of invasive or non-invasive mechanical ventilation, or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Need for FiO2 of 60% or more [ Time Frame: From date of randomization until the date of need for FiO2 of 60% or more, or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more assessed at 30 days, 90 days and 1 year [ Time Frame: 30 days, 90 days and 1 year after randomization ]
• Time spent in prone positioning among patients achieving the composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more [ Time Frame: Up to 7 days ]

Original Secondary Outcome Measures (submitted: May 8, 2020)

• Length of hospitalization [ Time Frame: Up to 4 weeks ]
• Adverse events of prone positioning (i.e., venous thromboembolism, pneumonia) [ Time Frame: Up to 7 days [or until hospital discharge] ]
• In-hospital all-cause mortality [ Time Frame: From date of randomization until the date of in-hospital all-cause mortality or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Invasive or non-invasive mechanical ventilation [ Time Frame: From date of randomization until the date of invasive or non-invasive mechanical ventilation, or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Need for FiO2 of 60% or more [ Time Frame: From date of randomization until the date of need for FiO2 of 60% or more, or date of hospital discharge, whichever came first, assessed up to 4 weeks ]
• Ventilator-free days (i.e., the number of days in hospital the patient was not on a ventilator) [ Time Frame: Up to 8 weeks ]
• Composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more assessed at 30 days, 90 days and 1 year [ Time Frame: 30 days, 90 days and 1 year after randomization ]
• Time spent in prone positioning among patients achieving the composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more [ Time Frame: Up to 7 days ]

Current Other Pre-specified Outcome Measures (submitted: September 14, 2020)

• Feasibility outcome: Change in oxygen saturation before and after prone positioning (to be measured for 72 hours beginning at the time of randomization), which will be calculated as: [ Time Frame: 72 hours ]
  I) The ratio between the patient's oxygen saturation and the amount of oxygen they're inspiring, II) Sustained (i.e., more than 5 minutes) drop in oxygen saturation less than 88% in the prone position on the same oxygen therapy required to maintain a saturation of >92% in the supine position.
• Feasibility outcome: Rate or serious adverse events [ Time Frame: Up to 7 days ]
  Rate of serious adverse events as identified through routine care by the patient's attending physician (e.g., venous thromboembolism, pneumonia) or through objective testing (i.e., death, transfer to the intensive care unit). Notably, bacterial pneumonia will be pragmatically defined through the combination of a chest x-ray report identifying evidence of pneumonia and the receipt of antibiotics known to treat pneumonia
• Feasibility outcome: Adherence to prone positioning [ Time Frame: Day 3 and day 7 ]
  The patients will be called on day 3 and 7. The research assistant/coordinator will ask the patient to estimate the number of hours spent in prone position.

Original Other Pre-specified Outcome Measures (submitted: May 8, 2020)

• Feasibility outcome: Change in oxygen saturation before and after prone positioning (to be measured for 72 hours beginning at the time of randomization), which will be calculated as: [ Time Frame: 72 hours ]
  I) The ratio between the patient's oxygen saturation and the amount of oxygen they're inspiring, II) Sustained (i.e., more than 5 minutes) drop in oxygen saturation less than 88% in the prone position on the same oxygen therapy required to maintain a saturation of >92% in the supine position.
• Feasibility outcome: Rate or serious adverse events [ Time Frame: Up to 7 days ]
  Rate of serious adverse events as identified through routine care by the patient's attending physician (e.g., venous thromboembolism, pneumonia) or through objective testing (i.e., death, transfer to the intensive care unit). Notably, bacterial pneumonia will be pragmatically defined through the combination of a chest x-ray report identifying evidence of pneumonia and the receipt of antibiotics known to treat pneumonia
• Feasibility outcome: Adherence to prone positioning [ Time Frame: Up to 72 hours ]
  The patients will be called each day for the first 72 hours by the research assistant/coordinator and will be asked to provide an estimate of the number of hours spent in prone position in the previous 24 hours.

Descriptive Information

• Brief Title: Prone Positioning for Patients on General Medical Wards With COVID19
• Official Title: Prone Positioning for Patients on General Medical Wards With COVID19: A Multicenter Pragmatic Randomized Trial [COVID-PRONE]
• Brief Summary: COVID-PRONE is a multicenter, pragmatic, unblinded, 2-arm, parallel, randomized controlled trial seeking to compare the pre-emptive prone positioning (i.e. encouraging patients to adopt a prone position before they require mechanical ventilation) to the control arm of standard care alone. Randomization will be stratified by site.

Detailed Description

COVID-PRONE is a multicenter, pragmatic, unblinded, 2-arm, parallel, randomized controlled trial. The intervention is not a medication or a medical device. Instead, the intervention is instructing patients to lie on their stomach while they are in bed.

Patients will be randomized to receive either standard-of-care or pre-emptive prone positioning while in bed plus standard of care. Randomization will be stratified by site. Patients randomized to prone positioning will be instructed to i) lie on their stomach supported by their arms and a pillow at the level of their shoulders and another pillow at the level of the pelvis, ii) immediately thereafter their oxygen saturation will be checked, iii) after a two hour period they can reposition to supine (but should be educated on the use of prone position and encouraged to adopt prone position as often as tolerated while in bed); the 2-hour period will be encouraged four times each day in addition to during sleep overnight.

Since there are limited data on the potential risks and benefits of prone positioning, a feasibility analysis will be performed after 30 patients are randomized to identify the rate of serious adverse events in the prone group (e.g., rate of pneumonia, death, intubation) and to understand the change in oxygenation as a result of prone positioning.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study is a multicenter, pragmatic, unblinded, 2-arm, parallel, randomized controlled trial.

Masking: None (Open Label)
Masking Description:

The study will be unblinded

Primary Purpose: Other

Condition

• Covid-19
• ARDS

Intervention

Other: Prone positioning

The intervention is prone positioning (i.e., instructing a patient to lie on their stomach while they are in bed) for 7 days or until the first of study hospital discharge or not requiring supplemental oxygen for >24 hours or study outcome. Patients will be asked to aim for prone positioning four times per day for at least two hours each time, and will be encouraged to sleep on their stomach at night.

Study Arms

• Experimental: PRONE POSITIONING
  Patients in this arm will be instructed to lie on their stomach while they are in bed for 7 days or until the first of study hospital discharge or not requiring supplemental oxygen for >24 hours or study outcome.
  Intervention: Other: Prone positioning
• No Intervention: STANDARD OF CARE
  Patients in this arm are not specifically instructed to lie on their stomach while they are in bed.

• Publications *: Fralick M, Colacci M, Munshi L, Venus K, Fidler L, Hussein H, Britto K, Fowler R, da Costa BR, Dhalla I, Dunbar-Yaffe R, Branfield Day L, MacMillan TE, Zipursky J, Carpenter T, Tang T, Cooke A, Hensel R, Bregger M, Gordon A, Worndl E, Go S, Mandelzweig K, Castellucci LA, Tamming D, Razak F, Verma AA; COVID Prone Study Investigators. Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE). BMJ. 2022 Mar 23;376:e068585. doi: 10.1136/bmj-2021-068585.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: March 16, 2021): 340
• Original Estimated Enrollment (submitted: May 8, 2020): 350
• Estimated Study Completion Date: June 1, 2021
• Estimated Primary Completion Date: June 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients ≥ 18 years of age
2. COVID-19 infection is suspected by the treating clinician or confirmed by diagnostic test
3. Able to lie on their stomach with verbal instruction
4. Requiring supplemental oxygen less than or equal to 50% FiO2
5. Capable to make treatment related decisions
6. Hospitalized in the last 48 hours with suspected or confirmed COVID-19 infection or diagnosed for nosocomial infection in the last 48 hours during their hospital stay

Exclusion Criteria:

1. Inability to follow commands (e.g., delirium, dementia)
2. indication for mechanical ventilation (e.g., reduced level of consciousness, rapid clinical deterioration)
3. contraindication to prone positioning (spinal cord injury, unstable c-spine, pelvic fracture, unstable airway, open chest or abdomen, anterior chest tube, recent abdominal surgery in past 14 days)
4. patients on home CPAP (continue positive airway pressure)
5. transfer from ICU in past 72 hours
6. need for telemetry at the time of randomization
7. pregnant (i.e., more than 20 weeks)
8. body mass index above 40 kg/m2 (based on clinician's assessment)
9. Recently completed or plan for intrathoracic or intra-abdominal surgical procedure
10. severe hemoptysis
11. pace-maker inserted in past 48 hours

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: Canada

Administrative Information

• NCT Number: NCT04383613
• Other Study ID Numbers: 2020-1
• 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: No

• Current Responsible Party: Unity Health Toronto
• Original Responsible Party: Same as current
• Current Study Sponsor: Unity Health Toronto
• Original Study Sponsor: Same as current

Collaborators

• Sunnybrook Health Sciences Centre
• Sinai Health System
• Toronto General Hospital
• University Health Network, Toronto
• William Osler Health System

Investigators

• Principal Investigator: Michael Fralick, MD, PhD; Sinai Health System
• Principal Investigator: Fahad Razak, MD, MSc; St. Michael's Hospital (Unity Health Toronto)
• Principal Investigator: Amol Verma, MD, MPhil; St. Michael's Hospital (Unity Health Toronto)

• PRS Account: Unity Health Toronto
• Verification Date: May 2021