Clinical trial NCT04344561: Incline Positioning in COVID-19 Patients for Improvement in Oxygen Saturation
Official title: UPright Incline Positioning in COVID-19 Patients for Oxygen SATuration Improvement With Hypoxemic Respiratory Failure (UPSAT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: COVID
Hypoxic Respiratory Failure
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Mechanical Ventilation
timeFrame: 72 hours
Secondary outcomes:
measure: Number of participants with supplemental oxygen requirements
timeFrame: 72 hours
measure: Mean oxyhemoglobin saturation
timeFrame: At 24, 48 and 72 hours
measure: Mean Nocturnal Oxyhemoglobin Saturation
timeFrame: Measured between 10pm and 6am daily, up to 72 hours
measure: Heart Rate
timeFrame: At 10, 24, 48 and 72 hours
measure: Respiratory Rate
timeFrame: At 10, 24, 48 and 72 hours
measure: Percentage of time in the assigned position
timeFrame: 72 hours
Other outcomes:
measure: Acute change in oxyhemoglobin saturation
timeFrame: During the final 7 minutes at each position, up to 72 hours
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Luu Pham, MD
role: PRINCIPAL_INVESTIGATOR
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