Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure (PRO-CARF)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Procedure: Standard oxygen therapy; Procedure: Awake prone positioning

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 Type: Interventional
• Enrollment (Actual): 430
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil Fray Antonio Alcalde
    • Guadalajara, Jalisco, Mexico, 45170
      • Hospital General de Occidente

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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%

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard oxygen therapy; 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.	Procedure: Standard oxygen therapy; Oxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%
Experimental: Awake prone positioning; 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%.	Procedure: Awake prone positioning; Patients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intubation rate	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total hours of prone position at day		28 days
Total number of prone sessions at day		28 days
Hours of the longest prone session each day		28 days
Change in oxygenation 1-hour after first prone session		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)	1 hour
Total days of prone positioning therapy		28 days
Adverse effects of prone positioning therapy		28 days
Mechanical ventilation days		28 days
Intensive care unit length of stay		28 days
Hospital length of stay		28 days
Hospital mortality		28 days

Collaborators and Investigators

• Sponsor: Hospital Civil de Guadalajara
• Investigators: Principal Investigator: Miguel Ibarra-Estrada, Investigator

Publications and helpful links

General Publications

• Ehrmann 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.
• 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.
• Ibarra-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.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2020
• Primary Completion (Actual): January 26, 2021
• Study Completion (Actual): January 26, 2021

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Severe; Prone positioning; High-flow nasal cannula
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 048/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No