COVID-19APPEX-19NCT04344587
Awake Prone Position for Early Hypoxemia in COVID-19
A study testing Self-prone position recommendation in people with COVID-19, run by Boston University at 13 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Self-prone position recommendation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 305 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 23 Apr 2020to 7 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
- Receiving ≥6 liters per minute of supplemental oxygen via nasal cannula, nasal pendant, or shovel mask
- Receiving supplemental oxygen via more aggressive methods (e.g. Venturi mask or non-rebreather mask)
- 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
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
University of Michigan
Ann Arbor, Michigan, 48109
Piedmont Atlanta
Atlanta, Georgia, 30309
Boston Medical Center
Boston, Massachusetts, 02118
St. Joseph's Hospital National Jewish Health
Denver, Colorado, 80218
Michael E. DeBakey Veteran Affairs Medical Center
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Kansas Medical Center
Kansas City, Kansas, 66160
Long Beach Medical Center - MemorialCare
Long Beach, California, 90806
Creighton University
Omaha, Nebraska, 68178
VCU Medical Center
Richmond, Virginia, 23219
Alvarado Hospital
San Diego, California, 92120
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Self-prone position recommendation, Usual care
- Keywords
- Prone position, Coronavirus, Inhalation oxygen therapy, Pragmatic Clinical Tria, Hypoxia
- Medical subject headings
- COVID-19, Coronavirus Infections, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Self-prone position recommendationOther
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
Usual careOther
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
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Participants in the intervention arm will receive a text message on their smartphones linking to the Qualtrics intervention website Receives: Other: Self-prone position recommendation |
| Usual care group | Active comparator | Participants in the usual care arm will receive a text message on their smartphone linking to the Qualtrics usual care website Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in respiratory status
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.
Measured: up to 30 days
Secondary outcomes (12)
Length of time participant spends in the prone position
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.
Measured: up to 30 days
Length of time participant spends in the supine position
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.
Measured: up to 30 days
Length of time participant spends lying on side
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.
Measured: up to 30 days
Length of time participant spends sitting up
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.
Measured: up to 30 days
Length of time participant spends standing or walking
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.
Measured: up to 30 days
Dyspnea or difficult/labored breathing
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.
Measured: up to 30 days
Discomfort with proning
Discomfort with proning (4-point ordinal scale: very comfortable, somewhat comfortable, somewhat uncomfortable, very uncomfortable)
Measured: up to 30 days
Length of hospital stay
Total number of days hospitalized will be abstracted from the electronic medical record.
Measured: up to 30 days
Invasive mechanical ventilation
Invasive mechanical ventilation will be abstracted from the electronic medical record.
Measured: up to 30 days
Loss of IV access as a consequence of turning in bed
Loss of IV access as a consequence of turning in bed will be reported by participant using monitoring surveys
Measured: up to 30 days
Acute respiratory distress syndrome (ARDS) diagnosis
ARDS diagnosis will be abstracted from the electronic medical record
Measured: up to 30 days
Hospital mortality
Hospital mortality will be abstracted from the electronic medical record
Measured: up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2020
- Study start23 Apr 2020
- Primary completion7 May 2021
- Study completion7 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Boston UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 305 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allan J Walkey, MD, Study director, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04344587
- Sponsor's protocol ID
- H-40070
- Acronym
- APPEX-19
- Status last verified
- Oct 2021
- First submitted
- 8 Apr 2020
- Last updated
- 1 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Garcia MA, Rampon GL, Doros G, Jia S, Jagan N, Gillmeyer K, Berical A, Hudspeth J, Ieong M, Modzelewski KL, Schechter-Perkins EM, Ross CS, Rucci JM, Simpson S, Walkey AJ, Bosch NA. Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial. Ann Am Thorac Soc. 2021 Sep;18(9):1560-1566. doi: 10.1513/AnnalsATS.202009-1124SD.
PubMed 33647225Rampon G, Jia S, Agrawal R, Arnold N, Martin-Quiromicrons A, Fischer EA, Malatack J, Jagan N, Sergew A, Case AH, Miller K, Tanios M, Doros G, Ross CS, Garcia MA, Gillmeyer KR, Griffiths NG, Jandali B, Modzelewski KL, Rucci JM, Simpson SQ, Walkey AJ, Bosch NA. Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial. Chest. 2022 Oct;162(4):782-791. doi: 10.1016/j.chest.2022.05.009. Epub 2022 May 18.
PubMed 35597286
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Awake Prone Position for Early Hypoxemia in COVID-19
- ClinicalTrials.gov ID
- NCT04344587
- Acronym / sponsor ID
- APPEX-19 / H-40070
- Conditions
- COVID-19
- Keywords
- Prone position, Coronavirus, Inhalation oxygen therapy, Pragmatic Clinical Tria, Hypoxia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 305 participants (actual)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Study start
- 23 Apr 2020 (actual)
- Primary completion
- 7 May 2021 (actual)
- Study completion
- 7 May 2021 (actual)
- First posted
- 14 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Self-prone position recommendationParticipants in the intervention arm will receive a text message on their smartphones linking to the Qualtrics intervention website |
| Usual care group | Active comparator | Other: Usual careParticipants in the usual care arm will receive a text message on their smartphone linking to the Qualtrics usual care website |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Self-prone position recommendationThe 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 | Intervention group |
| Usual careThe 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 | Other | Usual care group |
Primary outcome
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.
12 secondary outcomes
Length of time participant spends in the prone position
Time frame: up to 30 days
Length of time participant spends in the supine position
Time frame: up to 30 days
Length of time participant spends lying on side
Time frame: up to 30 days
Length of time participant spends sitting up
Time frame: up to 30 days
Length of time participant spends standing or walking
Time frame: up to 30 days
Dyspnea or difficult/labored breathing
Time frame: up to 30 days
Discomfort with proning
Time frame: up to 30 days
Length of hospital stay
Time frame: up to 30 days
Invasive mechanical ventilation
Time frame: up to 30 days
Loss of IV access as a consequence of turning in bed
Time frame: up to 30 days
Acute respiratory distress syndrome (ARDS) diagnosis
Time frame: up to 30 days
Hospital mortality
Time frame: up to 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 33647225Garcia MA, Rampon GL, Doros G, Jia S, Jagan N, Gillmeyer K, Berical A, Hudspeth J, Ieong M, Modzelewski KL, Schechter-Perkins EM, Ross CS, Rucci JM, Simpson S, Walkey AJ, Bosch NA. Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial. Ann Am Thorac Soc. 2021 Sep;18(9):1560-1566. doi: 10.1513/AnnalsATS.202009-1124SD.
- Derived from this study: PubMed 35597286Rampon G, Jia S, Agrawal R, Arnold N, Martin-Quiromicrons A, Fischer EA, Malatack J, Jagan N, Sergew A, Case AH, Miller K, Tanios M, Doros G, Ross CS, Garcia MA, Gillmeyer KR, Griffiths NG, Jandali B, Modzelewski KL, Rucci JM, Simpson SQ, Walkey AJ, Bosch NA. Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial. Chest. 2022 Oct;162(4):782-791. doi: 10.1016/j.chest.2022.05.009. Epub 2022 May 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allan J Walkey, MD study director
Boston University
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Self-prone position recommendation in people with COVID-19, run by Boston University at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in respiratory status (time frame: up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04344587, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021; AzTrials last refreshed its copy on 6 Nov 2026.