COVID-19 Patient Positioning Pragmatic Trial

December 22, 2021 updated by: Todd Rice, Vanderbilt University Medical Center

Pragmatic Trial Exploring Impact of Patient Positioning in the Management of Patients Infected With COVID-19: Supine vs. Prone

This study aims to determine if provider-recommended guidance on supine (on back) vs. prone (on stomach) positioning of patients testing positive for COVID-19 requiring supplemental oxygen, but not yet mechanically ventilated, improves outcomes in the inpatient setting. This study will be performed as a pragmatic clinical trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Disease Progression and Timing of Intervention The intervention described herein focuses on adjustment of patient positioning aimed at improving gas exchange and lung function in patients harboring COVID-19. This intervention will target the inpatient setting generally.

Scientific/Clinical Rationale for Approach Since emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) now designated coronavirus disease 2019 (COVID-19), one in six affected patients becomes seriously ill. The lung appears to be the most susceptible target organ, with a large swath of symptomatic patients struggling with mild upper respiratory tract illness and severe viral pneumonia resulting in respiratory failure. This respiratory failure is often fatal, with one study showing 28% non-survivors having experienced respiratory failure. Moreover, 81-97% of patients requiring mechanical ventilation do not survive.

Like its interaction with Severe Acute Respiratory Syndrome (SARS-CoV), angiotensin converting enzyme 2 (ACE2) is the functional receptor for COVID-19. Viral adherence to host-cell membrane associated ACE2 facilitates the proximity required for viral "spike" mediated genetic material injection. In COVID-19, this spike is 10-20 times more likely to bind ACE2 than SARS. ACE2 is expressed in 0.64% of all human lung cells, with 83% of those cells being alveolar epithelial type II. In addition, gene ontology enrichment analysis showed that the ACE2-expressing alveolar epithelial type II have high levels of multiple viral process-related genes, including regulatory genes for viral processes, viral life cycle, viral assembly, and viral genome replication, suggesting that the ACE2-expressing alveolar epithelial type II cells facilitate coronaviral replication in the lung. Thus, these cells likely serve as a ready reservoir for viral invasion. Perhaps more importantly, alveolar type II cells function to generate and recycle surfactant essential to respiratory activity. Surfactant defends against alveolar collapse at low lung volume and protects the lung from injuries/infections caused by inhaled particles and micro-organisms. In COVID-19, if these vital cells are being destroyed, alveolar failure may ensue with severe lung impairment. Thus, interventions that are aimed at improving pressure normalization and alveolar protection may be beneficial in these patients.

Prone positioning (PP) has long been used to combat hypoxemia in acute respiratory distress syndrome (ARDS). Improvements in gas exchange result from improved alveolar ventilation and blood flow redistribution with enhanced perfusion following. PP reduces lung over inflation and bolsters alveolar recruitment. PP also promotes uniformity of vertical pleural pressure gradients resulting in more uniform alveolar size. Considering these physiologic factors together, the investigators hypothesize PP serves to balance stress and strain within the lungs of non-critically ill patients with COVID-19 leading to improved outcomes compared to traditional supine positioning.

Prior Research Supporting the Positioning Model:

Multiple studies have been conducted that support the use of PP as a proactive treatment to combat hypoxemia in ARDS. Each year, approximately 170,000 people are diagnosed with ARDS, and those diagnosed face mortality rates between 25% and 40%. The use of PP stretches back to the 1970s, as providers began to search for ways to ameliorate ARDS symptomatology and reduce the then even higher levels of mortality associated with it. Following initial reports that PP significantly improved oxygenation in 70-80% of patients with ARDS, it was adopted as a standard treatment option. Initially, randomized clinical trials struggled to replicate these findings, citing multiple limitations to study enrollment and treatment standardization that made ascertaining conclusive results difficult. Only as RCT construction has been refined to accommodate for these limitations have the benefits of PP been more clearly demonstrated.

These beneficial effects have been recently upheld by the landmark PROSEVA study, a multicenter, prospective, randomized, controlled trial, that randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Their results demonstrated a significant improvement in both 28- and 90-day mortality rates: "the 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67)".

Per these positive findings, PP has been consistently shown to be an effective mechanism to increase oxygenation in patients with ARDS when implemented under the following conditions: early enlisting of treatment and its consistent maintenance for at least 16 hours per day, and with concurrent use of lung-protective therapies. Translating these findings towards treatment of COVID-19 positive patients seems promising given the similarity of manifested symptoms and complications.

Study Type

Interventional

Enrollment (Actual)

501

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Highland Park, Illinois, United States, 60035
        • Northshore University Healthsystem
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • This study will enroll all patients admitted to VUMC who test positive for COVID-19 and require supplemental oxygen, but are not yet mechanically ventilated.

Exclusion Criteria:

  • Patients admitted on mechanical ventilation will be excluded from enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Usual Care
Participants randomized to this arm will remain in their natural choice of position, which is anticipated to favor a supine, semi-recumbent position.
Other: Usual Care
No provider-recommendation, patients will remain in their natural choice of position
Active Comparator: Prone
Participants randomized to this arm will be encouraged to lay in a completely prone position for as much time as is tolerable during hospitalization.
Other: Prone
Provider-recommended guidance on prone positioning of patients
Other Names:
  • Proning

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Categorized on the Modified WHO Ordinal Scale by the Highest Level of Support on Day 5
Time Frame: 5 days post-randomization

The highest level of support on the 5th day after enrollment according to the following scale adjusted for patient status at enrollment according to the same scale and ranked by mean FIO2 within each category, as appropriate.

  • Death
  • ECMO
  • Mechanical ventilation (ranked by mean FIO2)
  • Non-invasive ventilation such as BiPAP (ranked by mean FIO2)
  • High flow nasal cannula, e.g. Optiflow, Vapotherm or other similar device (titrated by FiO2%) (ranked by mean FIO2)
  • Standard nasal cannula (titrated by L/min up to 15 L/min) or face mask (ranked by mean FIO2)
  • Room air
5 days post-randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FIO2
Time Frame: First 5 days post-randomization
For each day, the investigators will record the most intensive oxygen delivery mode and then, for that highest level of oxygen support device, the max FiO2 while exposed to that device.
First 5 days post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Todd W Rice, MD, MSc, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2020

Primary Completion (Actual)

December 17, 2020

Study Completion (Actual)

January 17, 2021

Study Registration Dates

First Submitted

April 20, 2020

First Submitted That Met QC Criteria

April 20, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

December 27, 2021

Last Update Submitted That Met QC Criteria

December 22, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200727

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.

IPD Sharing Time Frame

The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.

IPD Sharing Access Criteria

Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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