CORONA (COvid pRONe hypoxemiA): Prone Positioning for Hypoxemic COVID-19 Patients With Do-not-intubate Goals (CORONA)

A Prospective Randomized Trial of Prone Positioning Versus Usual Care for Patients With Do-not-intubate Goals of Care and Hypoxemic Respiratory Failure During the Coronavirus SARS-CoV-2 (COVID-19) Pandemic

The purpose of this trial is to determine whether Prone Positioning (PP) improves outcomes for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure due to probable COVID-19.

Study Overview

• Status: Unknown
• Conditions: COVID-19; Acute Respiratory Distress Syndrome; ARDS; Severe Acute Respiratory Syndrome Coronavirus 2; Hypoxemic Respiratory Failure
• Intervention / Treatment: Procedure: Prone Positioning (PP)

Detailed Description

As part of the management of COVID-19 related severe ARDS, the World Health Organization (WHO) recommends prone positioned mechanical ventilation. At this time, it is unclear whether there is a role for prone positioning (PP) of non-mechanically ventilated patients.

The objective of this trial is to determine whether PP improves outcomes for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure due to probable COVID-19.

Patients randomized to the intervention arm will continue with prone positioning until study inclusion criteria are no longer met, discharge from hospital, day 60 in hospital, or until death or discharge to hospice. Daily assessments will occur until day 60 or until the patient is discharged from hospital or is deceased. The investigators anticipate recruitment to be completed within 12 months of starting the trial.

• Study Type: Interventional
• Enrollment (Anticipated): 596
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ken Parhar, MD, MSc; Phone Number: 403-944-0735; Email: ken.parhar@ahs.ca
• Study Contact Backup: Name: Jason Weatherald, MD; Phone Number: 403-943-4779; Email: jcweathe@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Recruiting
      • Peter Lougheed Centre (PLC)
      • Contact: Jason Weatherald, MD
    • Calgary, Alberta, Canada, T2N 2T9
      • Recruiting
      • Foothills Hospital Intensive Care Unit
      • Contact: Ken Parhar, MD, MSc
    • Calgary, Alberta, Canada, T2V 1P9
      • Not yet recruiting
      • Rockyview General Hospital
    • Calgary, Alberta, Canada, T3M 1M4
      • Not yet recruiting
      • South Health Campus
      • Contact: Henry T Stelfox, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hospitalized patients with probable COVID-19. Probable is defined as Influenza like illness (ILI) symptoms OR confirmed COVID-19 exposure AND COVID-19 testing performed. ILI is defined as any one of the following symptoms including: fever, new or worsening cough, coryza, new or worsening dyspnea, or sore throat.
• Goals of care are do-not-intubate (R3 or M1/M2 in Alberta).
• Need for oxygen ≥2 L to maintain SpO2 ≥92%. If the patient is on long-term oxygen, the O2 requirements must be ≥2 L above their baseline.
• Patient can be positioned to and from prone to supine with minimal assistance (maximum one person assistance).

Exclusion Criteria:

• Decreased level of consciousness (Glasgow Coma Scale < 10) or precluding ability to self-reposition.
• Hemodynamic instability (Systolic Blood Pressure < 90 mmHg and or Lactate >5 mmol/L or HR >120, not responsive to fluid resuscitation).
• Complete bowel obstruction.
• Active upper gastrointestinal bleeding.
• Poor neck mobility or patient inability to lie prone comfortably.
• Unstable spine, femur, or pelvic fractures.
• Pregnancy - third trimester.
• Full resuscitation status including ICU and willingness to accept invasive mechanical ventilation (i.e. R1/R2 goals of care).
• Imminent palliation or end of life expected on admission (i.e. C1/C2 goals of care).

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
Experimental: Prone Positioning (PP); The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day.	Procedure: Prone Positioning (PP); The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day until the occurrence of a primary outcome event or hospital discharge. The target duration (dose) of PP is > 8 hours per day for up to 60 days, or until oxygen requirements are < 2 L per minute or < 2 L per minute above baseline home oxygen requirements.
No Intervention: Control - usual management; The control group will consist of standard medical care with no instructions or prompts to change positioning to staff or patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital mortality or discharge to hospice	In-hospital mortality or discharge to hospice at Day 60.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	An Adverse Event (AE) is any unfavourable or other finding (including clinically significant laboratory tests), symptom or disease occurring during the during of the study, whether or not it is considered to be related to the medicinal (investigational) product, not explicitly classified elsewhere in this protocol, and whether or not it is expected. A Serious Adverse Event (AE) is any unfavourable medical finding (including clinically significant laboratory tests) at any dose that: Results in death (primary outcome); Is life threatening; Results in persistent of significant disability or incapacity; Requires in in-patient hospitalisation or prolongation of Hospitalisation	60 days
Change in SpO2	Change in SpO2 during each PP session (SpO2 in prone position - SpO2 prior to prone positioning). Clinicians will be asked to record this change for the first proning session per shift (for 12 hour shifts this will result in 2 proning sessions being documented per 24 hour period, and for 8 hour shifts this will result in 3 proning sessions being documented per 24 hour period).	60 days
Hospital free days	Number of hospital free days in the 60 days after enrolment.	60 days
Admission to ICU	Admission to the Intensive Care Unit.	60 days
Intubation and mechanical ventilation	Patient is intubated and requires mechanical ventilation.	60 days
Initiation of non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).	Patient requires non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).	60 days
Oxygen-free days	The number of oxygen-free days at Day 60 (censored at discharge).	60 days
In-hospital death (time)	Time from admission to all-cause in-hospital death.	60 days
Death at 90 days	Death at 90 days.	90 days

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Alberta Health services
• Investigators: Principal Investigator: Ken Parhar, MD, MSc, University of Calgary; Principal Investigator: Jason Weatherald, MD, University of Calgary

Publications and helpful links

General Publications

• Weatherald J, Norrie J, Parhar KKS. Awake prone positioning in COVID-19: is tummy time ready for prime time? Lancet Respir Med. 2021 Dec;9(12):1347-1349. doi: 10.1016/S2213-2600(21)00368-4. Epub 2021 Aug 20. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Prone positioning; non-intubated
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Syndrome; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: REB20-0518

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No