Clinical trial NCT04383613: 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]
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Covid-19
ARDS
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Sunnybrook Health Sciences Centre
name: Sinai Health System
name: Toronto General Hospital
name: University Health Network, Toronto
name: William Osler Health System
First posted: 2020-05-12
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a multicenter, pragmatic, unblinded, 2-arm, parallel, randomized controlled trial.
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Composite outcome of in-hospital all-cause mortality, invasive or non-invasive mechanical ventilation, or need for FiO2 of 60% or more
timeFrame: 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 outcomes:
measure: Length of hospitalization
timeFrame: Up to 4 weeks [or until hospital discharge]
measure: Adverse events of prone positioning (i.e., venous thromboembolism, pneumonia)
timeFrame: Up to 7 days [or until hospital discharge]
measure: In-hospital all-cause mortality
timeFrame: 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
measure: Invasive or non-invasive mechanical ventilation
timeFrame: 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
measure: Need for FiO2 of 60% or more
timeFrame: 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
measure: 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
timeFrame: 30 days, 90 days and 1 year after randomization
measure: 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
timeFrame: Up to 7 days
Other outcomes:
measure: 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:
timeFrame: 72 hours
measure: Feasibility outcome: Rate or serious adverse events
timeFrame: Up to 7 days
measure: Feasibility outcome: Adherence to prone positioning
timeFrame: Day 3 and day 7
Locations:
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Etobicoke
country: Canada
facility: William Osler Health System
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sinai Health System
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre
state: Ontario
Study officials:
affiliation: Sinai Health System
name: Michael Fralick, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Michael's Hospital (Unity Health Toronto)
name: Fahad Razak, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Michael's Hospital (Unity Health Toronto)
name: Amol Verma, MD, MPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.