Incline Positioning in COVID-19 Patients for Improvement in Oxygen Saturation
Incline Positioning in COVID-19 Patients for Improvement in Oxygen Saturation
COVID-19 is a respiratory illness caused by SARS-CoV-2 with a range of symptoms from mild,
 self-limiting respiratory tract infections to severe progressive pneumonia, multiorgan
 dysfunction and death. A portion of individuals with COVID-19 experience life-threatening
 hypoxia requiring supplemental oxygen and mechanical ventilation. Management of hypoxia in
 this population is complicated by contraindication of non-invasive ventilation and
 limitations in access to mechanical ventilation and critical care staff given the clinical
 burden of disease. Positional therapy is readily deployable and may ultimately be used to
 treat COVID-19 related respiratory failure in resources limited settings; and, it has been
 demonstrated to improve oxygenation and is easy to implement in the clinical setting.

 The overall goal of this randomized controlled trial is to establish the feasibility of
 performing a randomized trial using a simple, minimally invasive positional therapy approach
 to improve hypoxia and reduce progression to mechanical ventilation. The objectives are to
 examine the effectiveness and feasibility of maintaining an inclined position in patients
 with confirmed or suspected COVID-19 associated hypoxemic respiratory failure. The
 investigators hypothesize that (1) oxyhemoglobin saturation will improve with therapy, (2)
 participants will tolerate and adhere to the intervention, and that (3) participants who
 adhere to positional therapy will have reduced rates of mechanical ventilation at 72 hours.
 If successful, this feasibility trial will demonstrate that a simple, readily deployed
 nocturnal postural maneuver is well tolerated and reverses underlying defects in ventilation
 and oxygenation due to COVID-19. It will also inform the design of a pivotal Phase III trial
 with estimates of sample sizes for clinically relevant outcomes.
Study Design: The investigators will conduct a pilot study to examine the acute effects of
 inclined posture on oxyhemoglobin saturation and the feasibility of conducting randomized
 controlled clinical trial among patients with confirmed or suspected COVID-19-associated
 hypoxia.

 In a subgroup of participants, the investigators will examine the acute effect of postural
 therapy (15-degree incline on hospital beds) on oxyhemoglobin saturation among hypoxic
 patients to establish a biologic response. The investigators will enroll a subset of
 participants (n=16) who will lie supine on hospital beds, which will be placed in the
 horizontal (flat) or 15-degree inclined (reverse Trendelenberg) orientation in random order.
 During this time, the investigators will continuous record pulse oximetry, pulse rate and
 variations in peripheral arterial tone with WatchPAT one devices. Subjects will be visually
 monitored for work of breathing during this time. If work of breathing becomes excessive, as
 defined as a sustain respiratory rate of >25 and an increase of >5 breaths per minute from
 baseline, or oxygenation decreases below 88% for > 30 seconds in the inclined position, then
 maneuvers will be stopped. If the patient meets these criteria in the flat position, then the
 investigators sit the patient upright, and allow breathing to return to baseline before
 examining responses in the inclined position.

 The investigators will randomize participants to have beds placed in 15-degree incline or
 usual care (ad-lib positioning) for 72 hours. During the first night in a subgroup of
 participants, the investigators will record oxygenation, sleep wake state and markers of
 sympathetic activity with WatchPAT One devices, which can obtain cardiopulmonary parameters
 with high temporal resolution. The investigators will obtain vital signs from the data
 warehouse, which archives telemetry data with a maximum sampling frequency of 1 minute. The
 investigators will record adherence with continuous accelerometry sensors placed on the bed
 rails and on the anterolateral surface of participants' chests to measure bed and
 participants' positions, respectively. Aside from position, participants will receive usual
 treatment for COVID-19.

 The investigators will enroll in 3 phases. At the end of each phase, the investigators will
 assess for completion of milestones for proceeding to the subsequent phase, as detailed
 below:

 1. Pilot Study: The investigators will pilot the study in 16 participants to obtain
 critical information on logistics of conducting the trial including performance of
 recording instruments in a biocontainment environment, to examine the feasibility of the
 intervention, perform preliminary safety evaluations to ascertain potential harm and to
 determine whether the intervention results in a meaningful difference in body position.

 2. Phase II RCT: If inclined therapy results in a difference in body position and no
 significant safety issues were detected, the investigators will conduct a phase II
 randomized-controlled trial (RCT) in 70 participants (see sample size calculation below)
 to estimate the effect size of inclined position on rates of intubation and determine
 sample size for a Phase III trial.

 Randomization will be occur in both phases and will be stratified by study phase and study
 site.
Inclusion Criteria:

 -  COVID-19 positive

 -  Pneumonia defined as hospitalization for acute (< 7 days) onset of symptoms (cough,
 sputum production, or dyspnea).

 -  Hypoxemia defined as ≥ 2 L/min oxygen

 Exclusion Criteria:

 -  Intubation

 -  Inability to lie supine