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

Prone Positioning for Patients on General Medical Wards With COVID19: A Multicenter Pragmatic Randomized Trial [COVID-PRONE]

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid-19; ARDS
• Intervention / Treatment: Other: Prone positioning

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
• Enrollment (Anticipated): 340
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada
      • William Osler Health System
    • Etobicoke, Ontario, Canada
      • William Osler Health System
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Sinai Health System
    • Toronto, Ontario, Canada
      • St. Joseph's Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
NO_INTERVENTION: STANDARD OF CARE; Patients in this arm are not specifically instructed to lie on their stomach while they are in bed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more	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

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of hospitalization	Up to 4 weeks [or until hospital discharge]
Adverse events of prone positioning (i.e., venous thromboembolism, pneumonia)	Up to 7 days [or until hospital discharge]
In-hospital all-cause mortality	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	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	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	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	Up to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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:	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.	72 hours
Feasibility outcome: Rate or serious adverse events	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	Up to 7 days
Feasibility outcome: Adherence to prone positioning	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.	Day 3 and day 7

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: University Health Network, Toronto; Sunnybrook Health Sciences Centre; Sinai Health System; Toronto General Hospital; 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)

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2020
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): June 1, 2021

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (ACTUAL): May 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 2020-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No