Prone Positioning on Admission for Hospitalized COVID-19 Pneumonia Protocol

In hypoxic respiratory failure, placing patients in the prone position improves ventilation
to perfusion matching, alveolar recruitment, and alveolar to arterial oxygen gradients.
Specifically, in Acute Respiratory Distress Syndrome ARDS, proning intubated patients
improves overall mortality. With the emergence of SARS-COV-2, hospitals around the world have
seen a marked increase in patients with acute hypoxic respiratory failure and ARDS. This
surge in cases has prompted a search for more effective strategies to reduce intubation and
improve patient morbidity and mortality. One such strategy is that of voluntary proning, in
which awake patients are instructed to prone themselves (Early PP With High Flow Nasal
Cannula (HFNC) Versus HFNC in COVID-19 Induced Moderate to Severe ARDS) (COVID-19
smArtphone-based Trial of Non-ICU Admission Prone Positioning (CATNAP)).

This trial proposes a voluntary proning strategy in patients admitted to the hospital, not
yet requiring mechanical ventilation. Given the clear evidence that proning improves outcomes
in ARDS, investigators hypothesize that early, voluntary self-proning may prevent intubation
and improve mortality in patients with SARS-COV-2.

Methods

This is a pilot study of up to 100 participants at UCHealth facilities.

Patients will be assessed if they can self prone safely and be assessed against inclusion and
exclusion criteria within 12 hours of admission and randomized to either prone or supine
positioning. Baseline labs will be measured and all participants will be monitored
continuously via pulse oximetry.

The Standard Supine Control Group will utilize standard oxygen (O2) device in supine position
at approximately 30-60 degrees to target peripheral capillary oxygen saturation (SpO2) >90%
and the participant or nurse will document time in non-supine position.

The Prone Experimental Group will position patient in approximately 15-degree reverse
trendelenburg and prone using pillows for comfort. The participant will be asked to rotate to
prone positioning every 2 hours while awake and encourage to sleep prone overnight as
possible with a goal of 10-12 hours daily. Patient to log all time prone.

Treatment Failure may occur and termination of Intermittent Prone Positioning will occur.
This is defined as respiratory distress or a decrease in O2 saturations <90% for more than 2
minutes as determined by bedside nursing or per virtual pulse oximetry monitoring
notifications during the study on two consecutive occasions. The participant will be returned
to supine positioning and follow standard supine oxygenation. The participant can be
re-challenged in the prone position after the participant stabilizes for 2 hours. The
participant can also choose to stop proning and would be considered a treatment failures.

Statistical Analysis and Sample Size In New York City the intubation rate has been reported
at 1/3 of COVID-19 positive patients admitted to the hospital. The table below shows the
sample size needed for a binomial outcome of intubation when 50% of the sample is randomized
to Prone Positioning (PP):

Alpha 0.05 0.05 0.05 0.05 Beta 0.80 0.80 0.80 0.80 Probability of intubation with PP 0.05
0.10 0.15 0.20 Probability of intubation 0.33 0.33 0.33 0.33 Proportion receiving PP 0.50
0.50 0.50 0.50 Sample size 33 39 56 97

Expecting a 13% decrease in intubations with the prone position, investigators will use a
sample size of N = 100 (50 per group) in order to have 80% power with a two-sided alpha =
0.05 for logistic regression. ANCOVA will be used to evaluate continuous, secondary variables
in order to adjust for covariates. The study is powered for the primary outcome of intubation
or no intubation. No adjustments will be made for the secondary endpoints.

The investigators and statistician will validate the data and the study will be subject to
institutional quality assurance reviews.