Covid19PRO-CARFNCT04477655
Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure
A study testing Awake prone positioning and Standard oxygen therapy in people with Covid19, run by Hospital Civil de Guadalajara at 2 sites in Mexico.
Trial summary
Besides protective ventilation with low tidal volumes, prone positioning is a proven intervention to decrease mortality in mechanically ventilated patients with moderate-severe acute respiratory distress syndrome. However, the evidence of this strategy in awake non-intubated patients is scarce. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid19
- What is being tested?
- Awake prone positioning and Standard oxygen therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 2 sitesMexico
- Study dates
- 3 May 2020to 26 Jan 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients with confirmed COVID-19, and requirement of a fraction of inspired oxygen (FiO2) ≥30% through high-flow nasal cannula (HFNC) to maintain a capillary saturation of ≥90%
Who cannot join
- Less than 18 years-old
- Pregnancy
- Patients with immediate need of invasive mechanical ventilation
- Contraindications for prone positioning therapy
- Do-not-resuscitate or do-not-intubate order
- Refusal of the patient or decision maker to enroll in the study
Trial locations and contacts
2 sites in 1 country.
Mexico2 sites
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, 44280
Hospital General de Occidente
Guadalajara, Jalisco, 45170
About this study
Official title: Prone Positioning in Non-intubated Patients With Severe COVID-19: a Randomized Controlled Trial
Besides protective ventilation with low tidal volumes, prone positioning is a proven intervention to decrease mortality in mechanically ventilated patients with moderate-severe acute respiratory distress syndrome. However, the evidence of this strategy in awake non-intubated patients is scarce. The investigators will perform a randomized controlled trial to define if prone positioning can reduce the requirement of mechanical ventilation.
Read the detailed description
Despite ongoing trials of antivirals and immunomodulatory therapies against COVID-19, the treatment of moderate/severe disease is mainly supportive, including oxygen therapy and invasive mechanical ventilation when impending respiratory failure is established. Moreover, the associated mortality among mechanically intubated patients is overwhelmingly high. Prone position relieves the dependent lung regions from the compressive forces of the mediastinum's weight, leading to homogenization of the gas:tissue ratio between ventral and dorsal lung regions. According to a few case series, and observational non-randomized studies with small sample sizes, there is a consistent improvement in oxygenation in COVID-19 patients during prone positioning, however there are no clinical evidence that this improvement is associated with a decrease in the risk of invasive mechanical ventilation. Considering that prone positioning is a low cost, low risk and widely available therapy, more high quality evidence is needed, to determine if the benefits of prone positioning in awake patients also include a lower requirement of mechanical ventilation.
- Conditions
- Covid19
- Being tested
- Awake prone positioning, Standard oxygen therapy
- Keywords
- COVID-19, Severe, Prone positioning, High-flow nasal cannula
- Medical subject headings
- COVID-19, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Awake prone positioningProcedure or surgery
Patients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible.
Standard oxygen therapyProcedure or surgery
Oxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%
| Study group | Role | What they receive |
|---|---|---|
| Standard oxygen therapy | Active comparator | Oxygen therapy through high flow nasal cannula (HFNC). Continuous monitoring of vital signs. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Prone positioning will be allowed as a rescue therapy. Receives: Procedure: Standard oxygen therapy |
| Awake prone positioning | Experimental | Oxygen therapy through high flow nasal cannula (HFNC). Patients will be asked to remain in prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Receives: Procedure: Awake prone positioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intubation rate
Measured: 28 days
Secondary outcomes (11)
Total hours of prone position at day
Measured: 28 days
Total number of prone sessions at day
Measured: 28 days
Hours of the longest prone session each day
Measured: 28 days
Change in oxygenation 1-hour after first prone session
Measured: 1 hour
Change in the ROX-index 1-hour after first prone session
The change in the Ratio of Oxygen saturation to respiratory rate (ROX-index)
Measured: 1 hour
Total days of prone positioning therapy
Measured: 28 days
Adverse effects of prone positioning therapy
Measured: 28 days
Mechanical ventilation days
Measured: 28 days
Intensive care unit length of stay
Measured: 28 days
Hospital length of stay
Measured: 28 days
Hospital mortality
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start3 May 2020
- Primary completion26 Jan 2021
- Study completion26 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 430 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Civil de Guadalajara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miguel Á Ibarra-Estrada, Hospital Civil de Guadalajara
- Investigators
- Miguel Ibarra-Estrada, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04477655
- Sponsor's protocol ID
- 048/20
- Acronym
- PRO-CARF
- Status last verified
- Apr 2021
- First submitted
- 15 Jul 2020
- Last updated
- 13 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ibarra-Estrada M, Li J, Pavlov I, Perez Y, Roca O, Tavernier E, McNicholas B, Vines D, Marin-Rosales M, Vargas-Obieta A, Garcia-Salcido R, Aguirre-Diaz SA, Lopez-Pulgarin JA, Chavez-Pena Q, Mijangos-Mendez JC, Aguirre-Avalos G, Ehrmann S, Laffey JG. Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial. Crit Care. 2022 Mar 28;26(1):84. doi: 10.1186/s13054-022-03950-0.
PubMed 35346319Ehrmann S, Li J, Ibarra-Estrada M, Perez Y, Pavlov I, McNicholas B, Roca O, Mirza S, Vines D, Garcia-Salcido R, Aguirre-Avalos G, Trump MW, Nay MA, Dellamonica J, Nseir S, Mogri I, Cosgrave D, Jayaraman D, Masclans JR, Laffey JG, Tavernier E; Awake Prone Positioning Meta-Trial Group. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021 Dec;9(12):1387-1395. doi: 10.1016/S2213-2600(21)00356-8. Epub 2021 Aug 20.
PubMed 34425070Ibarra-Estrada MA, Marin-Rosales M, Garcia-Salcido R, Aguirre-Diaz SA, Vargas-Obieta A, Chavez-Pena Q, Lopez-Pulgarin JA, Mijangos-Mendez JC, Aguirre-Avalos G. Prone positioning in non-intubated patients with COVID-19 associated acute respiratory failure, the PRO-CARF trial: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 23;21(1):940. doi: 10.1186/s13063-020-04882-2.
PubMed 33225990
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prone Positioning in Non-intubated Patients With Severe COVID-19: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04477655
- Acronym / sponsor ID
- PRO-CARF / 048/20
- Conditions
- Covid19
- Keywords
- COVID-19, Severe, Prone positioning, High-flow nasal cannula
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 430 participants (actual)
- Lead sponsor
- Hospital Civil de GuadalajaraUniversity, hospital or other
- Study start
- 3 May 2020 (actual)
- Primary completion
- 26 Jan 2021 (actual)
- Study completion
- 26 Jan 2021 (actual)
- First posted
- 20 Jul 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.
Besides protective ventilation with low tidal volumes, prone positioning is a proven intervention to decrease mortality in mechanically ventilated patients with moderate-severe acute respiratory distress syndrome. However, the evidence of this strategy in awake non-intubated patients is scarce. The investigators will perform a randomized controlled trial to define if prone positioning can reduce the requirement of mechanical ventilation.
Detailed description
Despite ongoing trials of antivirals and immunomodulatory therapies against COVID-19, the treatment of moderate/severe disease is mainly supportive, including oxygen therapy and invasive mechanical ventilation when impending respiratory failure is established. Moreover, the associated mortality among mechanically intubated patients is overwhelmingly high. Prone position relieves the dependent lung regions from the compressive forces of the mediastinum's weight, leading to homogenization of the gas:tissue ratio between ventral and dorsal lung regions. According to a few case series, and observational non-randomized studies with small sample sizes, there is a consistent improvement in oxygenation in COVID-19 patients during prone positioning, however there are no clinical evidence that this improvement is associated with a decrease in the risk of invasive mechanical ventilation. Considering that prone positioning is a low cost, low risk and widely available therapy, more high quality evidence is needed, to determine if the benefits of prone positioning in awake patients also include a lower requirement of mechanical ventilation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard oxygen therapy | Active comparator | Procedure: Standard oxygen therapyOxygen therapy through high flow nasal cannula (HFNC). Continuous monitoring of vital signs. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Prone positioning will be allowed as a rescue therapy. |
| Awake prone positioning | Experimental | Procedure: Awake prone positioningOxygen therapy through high flow nasal cannula (HFNC). Patients will be asked to remain in prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients with confirmed COVID-19, and requirement of a fraction of inspired oxygen (FiO2) ≥30% through high-flow nasal cannula (HFNC) to maintain a capillary saturation of ≥90%
Key exclusion criteria (6 listed)
- Less than 18 years-old
- Pregnancy
- Patients with immediate need of invasive mechanical ventilation
- Contraindications for prone positioning therapy
- Do-not-resuscitate or do-not-intubate order
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 |
|---|---|---|
| Awake prone positioningPatients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible. | Procedure or surgery | Awake prone positioning |
| Standard oxygen therapyOxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92% | Procedure or surgery | Standard oxygen therapy |
Primary outcome
Intubation rate
Time frame: 28 days
11 secondary outcomes
Total hours of prone position at day
Time frame: 28 days
Total number of prone sessions at day
Time frame: 28 days
Hours of the longest prone session each day
Time frame: 28 days
Change in oxygenation 1-hour after first prone session
Time frame: 1 hour
Change in the ROX-index 1-hour after first prone session
Time frame: 1 hour
Total days of prone positioning therapy
Time frame: 28 days
Adverse effects of prone positioning therapy
Time frame: 28 days
Mechanical ventilation days
Time frame: 28 days
Intensive care unit length of stay
Time frame: 28 days
Hospital length of stay
Time frame: 28 days
Hospital mortality
Time frame: 28 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 13 Apr 2021.
- Derived from this study: PubMed 35346319Ibarra-Estrada M, Li J, Pavlov I, Perez Y, Roca O, Tavernier E, McNicholas B, Vines D, Marin-Rosales M, Vargas-Obieta A, Garcia-Salcido R, Aguirre-Diaz SA, Lopez-Pulgarin JA, Chavez-Pena Q, Mijangos-Mendez JC, Aguirre-Avalos G, Ehrmann S, Laffey JG. Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial. Crit Care. 2022 Mar 28;26(1):84. doi: 10.1186/s13054-022-03950-0.
- Derived from this study: PubMed 34425070Ehrmann S, Li J, Ibarra-Estrada M, Perez Y, Pavlov I, McNicholas B, Roca O, Mirza S, Vines D, Garcia-Salcido R, Aguirre-Avalos G, Trump MW, Nay MA, Dellamonica J, Nseir S, Mogri I, Cosgrave D, Jayaraman D, Masclans JR, Laffey JG, Tavernier E; Awake Prone Positioning Meta-Trial Group. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021 Dec;9(12):1387-1395. doi: 10.1016/S2213-2600(21)00356-8. Epub 2021 Aug 20.
- Derived from this study: PubMed 33225990Ibarra-Estrada MA, Marin-Rosales M, Garcia-Salcido R, Aguirre-Diaz SA, Vargas-Obieta A, Chavez-Pena Q, Lopez-Pulgarin JA, Mijangos-Mendez JC, Aguirre-Avalos G. Prone positioning in non-intubated patients with COVID-19 associated acute respiratory failure, the PRO-CARF trial: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 23;21(1):940. doi: 10.1186/s13063-020-04882-2.
- 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.
Miguel Ibarra-Estrada principal investigator
Investigator
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Awake prone positioning and Standard oxygen therapy in people with Covid19, run by Hospital Civil de Guadalajara at 2 sites in Mexico.
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 1 inclusion and 6 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 13 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Mexico. 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?
Intubation rate (time frame: 28 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 NCT04477655, which also lists 3 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 13 Apr 2021; AzTrials last refreshed its copy on 6 Nov 2026.