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: November 10, 2020
• Sponsor: Boston University
• Information provided by (Responsible Party): Boston University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Other: Self-prone position recommendation; Other: Usual care	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 560 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Awake Prone Position for Early Hypoxemia in COVID-19
• Actual Study Start Date: April 23, 2020
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group; Participants in the intervention arm will receive a text message on their smartphones linking to the Qualtrics intervention website	Other: Self-prone position recommendation; The Qualtrics self-prone position recommendation intervention website will include the following sections: Welcome message; Educational review of the potential benefits of prone positioning; How-To guide to safely "prone" in a hospital bed; A recommendation to "prone" while lying in bed (4 times for 1-2 hours each during the day and at night every 24 hours).; 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
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	Other: Usual care; The Qualtrics usual care website will include the following sections: Welcome message; 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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Discomfort with proning [ Time Frame: up to 30 days ]
   Discomfort with proning (4-point ordinal scale: very comfortable, somewhat comfortable, somewhat uncomfortable, very uncomfortable)
8. Length of hospital stay [ Time Frame: up to 30 days ]
   Total number of days hospitalized will be abstracted from the electronic medical record.
9. Invasive mechanical ventilation [ Time Frame: up to 30 days ]
   Invasive mechanical ventilation will be abstracted from the electronic medical record.
10. 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
11. Acute respiratory distress syndrome (ARDS) diagnosis [ Time Frame: up to 30 days ]
    ARDS diagnosis will be abstracted from the electronic medical record
12. Hospital mortality [ Time Frame: up to 30 days ]
    Hospital mortality will be abstracted from the electronic medical record

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Alvarado Hospital

San Diego, California, United States, 92120

United States, Colorado

St. Joseph's Hospital National Jewish Health

Denver, Colorado, United States, 80218

United States, District of Columbia

MedStar Georgetown University Hospital

Washington, District of Columbia, United States, 20007

United States, Georgia

Piedmont Atlanta

Atlanta, Georgia, United States, 30309

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Nebraska

Creighton University

Omaha, Nebraska, United States, 68178

United States, Texas

Michael E. DeBakey Veteran Affairs Medical Center

Houston, Texas, United States, 77030

United States, Virginia

VCU Medical Center

Richmond, Virginia, United States, 23219

Spain

Hospital Universitario La Paz

Madrid, Spain, 28049

Sponsors and Collaborators

Boston University

Investigators

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

More Information

• Responsible Party: Boston University
• ClinicalTrials.gov Identifier: NCT04344587
• Other Study ID Numbers: H-40070
• First Posted: April 14, 2020
• Last Update Posted: November 10, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Boston University:

Prone position; Coronavirus; Inhalation oxygen therapy; Pragmatic Clinical Tria; Hypoxia

Additional relevant MeSH terms:

Hypoxia; Signs and Symptoms, Respiratory