Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19)

• ClinicalTrials.gov Identifier: NCT04344587
• Recruitment Status: Enrolling by invitation
• First Posted: April 14, 2020
• Last Update Posted: December 29, 2020
• Sponsor: Boston University
• Information provided by (Responsible Party): Boston University

Tracking Information

• First Submitted Date: April 8, 2020
• First Posted Date: April 14, 2020
• Last Update Posted Date: December 29, 2020
• Actual Study Start Date: April 23, 2020
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 9, 2020)

Change in respiratory status [ Time Frame: up to 30 days ]

Change in respiratory status will be defined as:1) admission to the ICU and/or a 2) an increase in supplemental oxygen delivery (defined as an increase in oxygen delivery rate of ≥2 liter per minute compared to the oxygen delivery rate at the time of intervention or usual care text message that is sustained for ≥12 or more hours OR the switch to an oxygen delivery method that increases the level of supplemental oxygen.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 9, 2020)

• Length of time participant spends in the prone position [ Time Frame: up to 30 days ]
  Length of time in the prone position will be assessed from the smartphone survey and measured in categories of no time, up to 6 hours, 6 hours to 11 hours, 12 hours or more.
• Length of time participant spends in the supine position [ Time Frame: up to 30 days ]
  Length of time in the supine/lying on back position will be assessed from the smartphone survey and measured in categories of no time, up to 6 hours, 6 hours to 11 hours, 12 hours or more.
• Length of time participant spends lying on side [ Time Frame: up to 30 days ]
  Length of time lying on side will be assessed from the smartphone survey and measured in categories of no time, up to 6 hours, 6 hours to 11 hours, 12 hours or more.
• Length of time participant spends sitting up [ Time Frame: up to 30 days ]
  Length of time sitting up will be assessed from the smartphone survey and measured in categories of no time, up to 6 hours, 6 hours to 11 hours, 12 hours or more.
• Length of time participant spends standing or walking [ Time Frame: up to 30 days ]
  Length of time standing or walking will be assessed from the smartphone survey and measured in categories of no time, up to 6 hours, 6 hours to 11 hours, 12 hours or more.
• Dyspnea or difficult/labored breathing [ Time Frame: up to 30 days ]
  Dyspnea will be assessed by the modified Borg Dyspnea Score (10-point ordinal scale) from 1= nothing at all to 10= maximal. Higher scores indicate more dyspnea.
• Discomfort with proning [ Time Frame: up to 30 days ]
  Discomfort with proning (4-point ordinal scale: very comfortable, somewhat comfortable, somewhat uncomfortable, very uncomfortable)
• Length of hospital stay [ Time Frame: up to 30 days ]
  Total number of days hospitalized will be abstracted from the electronic medical record.
• Invasive mechanical ventilation [ Time Frame: up to 30 days ]
  Invasive mechanical ventilation will be abstracted from the electronic medical record.
• Loss of IV access as a consequence of turning in bed [ Time Frame: up to 30 days ]
  Loss of IV access as a consequence of turning in bed will be reported by participant using monitoring surveys
• Acute respiratory distress syndrome (ARDS) diagnosis [ Time Frame: up to 30 days ]
  ARDS diagnosis will be abstracted from the electronic medical record
• Hospital mortality [ Time Frame: up to 30 days ]
  Hospital mortality will be abstracted from the electronic medical record

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Awake Prone Position for Early Hypoxemia in COVID-19
• Official Title: Awake Prone Position for Early Hypoxemia in COVID-19

Brief Summary

Prone positioning is a well studied and validated treatment for severe acute respiratory distress syndrome (ARDS), however there are no randomized studies on the use of prone positioning in the non-intubated patient. It is unknown if this intervention would be helpful in preventing further respiratory deterioration in terms of increasing supplemental oxygen requirements, endotracheal intubation, and ICU admission.

The Awake Prone Position for Early hypoxemia in COVID-19 (APPEX-19) Study is a pragmatic adaptive randomized controlled unblinded trial. APPEX-19 randomizes non-ICU patients with COVID-19 or who are under evaluation for COVID-19 to lie in a prone position (i.e, with their stomach and chest facing down) or to usual care.

Detailed Description

The purpose of this multi-site trial is to investigate the use of prone positioning in SARS-CoV-2 infected patients who are not intubated. The APPEX-19 study is a pragmatic adaptive randomized controlled unblinded trial. The study compares a smartphone tool that recommends non-ICU patients with COVID-19 or who are under evaluation for COVID-19 to lie in a prone position (i.e, with their stomach and chest facing down) to usual care.

Participants who are assigned to the intervention arm will receive a text message containing a link to an online website that reviews how to safely self-prone position and a recommendation to self-prone position 4 times for 1-2 hours each during the day and at night every 24 hours. Participants will also receive twice daily reminders to self-prone using the same smartphone platform.

All participants will receive twice daily Qualtrics online surveys to answer questions about which body positions they used in bed and their level of comfort and shortness of breath. Participants will receive these twice daily text messages until they are discharged, until they are transferred to the ICU, until they die, until their lung function declines, or until 14 days pass since enrollment. Thus, most participants will receive twice daily text messages for about 1 week; it is expected that almost all patients will receive twice daily text messages for no longer than 14 days. Medical charts will be reviewed daily to track routine clinical data to determine outcomes.

Boston Medical Center (BMC) / Boston University will be one of the 16 sites and the data coordinating center for this multisite trial. The unique design of the study means that if evidence accumulates that one treatment is better than the other, more participants will be chosen to receive the prone position intervention that works over time. Thus, the trial will both show what works, implement what works, and make sure that the most participants receive the treatment that works.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care
• Condition: COVID-19

Intervention

• Other: Self-prone position recommendation

  The Qualtrics self-prone position recommendation intervention website will include the following sections:

  1. Welcome message
  2. Educational review of the potential benefits of prone positioning
  3. How-To guide to safely "prone" in a hospital bed
  4. A recommendation to "prone" while lying in bed (4 times for 1-2 hours each during the day and at night every 24 hours).
  5. A reminder to keep track of the time spent in 1) prone position, 2) lying flat on back, 3) lying on side, 4) sitting up, and 5) standing or walking
• Other: Usual care

  The Qualtrics usual care website will include the following sections:

  1. Welcome message
  2. A reminder to keep track of the time spent in 1) prone position, 2) lying flat on back, 3) lying on side, 4) sitting up, and 5) standing or walking

Study Arms

• Experimental: Intervention group
  Participants in the intervention arm will receive a text message on their smartphones linking to the Qualtrics intervention website
  Intervention: Other: Self-prone position recommendation
• Active Comparator: Usual care group
  Participants in the usual care arm will receive a text message on their smartphone linking to the Qualtrics usual care website
  Intervention: Other: Usual care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: May 11, 2020): 560
• Original Estimated Enrollment (submitted: April 9, 2020): 380
• Estimated Study Completion Date: April 2021
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Assigned to or admitted to a COVID-19 ward team at a participating site (these teams only admit patients who are under investigation for COVID-19 or who have confirmed COVID-19 infection) via the emergency department (ED) within the last 24 hours
• Have access to their own functioning smartphone in the hospital room
• English or Spanish-speaking
• Ability to read simple instructions and answer simple written questions

Exclusion Criteria:

Baseline patient factors

• Inability to operate the hospital bed
• Inability to lie flat comfortably
• Inability to lie flat without shortness of breath
• Inability to turn over independently

Medical comorbidities

• Hemoptysis in the last 2 days
• Prior lung transplant
• Dementia

Acute issues

• Deep venous thrombosis treated for less than 2 days
• Unstable spine, femur, or pelvic fractures
• Mean arterial pressure lower than 65 mmHg

Recent interventions

• Chest tube in place
• Tracheal surgery or sternotomy during the previous 15 days
• Serious facial trauma or facial surgery during the previous 15 days
• Cardiac pacemaker inserted in the last 2 days

Other

• Pregnancy
• Comfort measures only status
• Prisoner

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain, United States

Administrative Information

• NCT Number: NCT04344587
• Other Study ID Numbers: H-40070
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Boston University
• Study Sponsor: Boston University
• Collaborators: Not Provided

Investigators

• Study Director: Allan J Walkey, MD; Boston University

• PRS Account: Boston University
• Verification Date: December 2020