Early Versus Delayed Intubation of Patients With COVID-19

Study Overview
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Brief Summary
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Although management of acute hypoxemic respiratory failure associated with coronavirus disease 2019 (COVID-19) often includes mechanical ventilation, the optimal timing of initiation of invasive mechanical ventilation remains unknown. We hypothesise that a randomized controlled trial comparing early intubation as opposed to delayed intubation among patients with COVID-19 suffering from severe acute hypoxemic respiratory failure is feasible.

Detailed Description
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A common manifestation of COVID-19 is severe acute hypoxemic respiratory failure. Management of acute hypoxemic respiratory failure associated with COVID-19 often includes mechanical ventilation. The optimal timing of initiation of invasive mechanical ventilation remains unknown. On the one hand, early initiation of invasive mechanical ventilation (i.e. early endotracheal intubation) has been advocated as a means to reduce subsequent possible aerosolization of the virus, as would happen by alternate means of oxygenation/ventilation allowing air leaks. Also, early intubation may prevent the induction of self-inflicted lung injury in patients who breath spontaneously and have high respiratory drive and, therefore, large transpulmonary pressure swings. On the other hand, delaying intubation, by trying alternate means of oxygenation/ventilation, may mean that some of the patients may not be intubated at all and therefore will be protected from the adverse events of invasive mechanical ventilation (such as ventilator-induced lung injury, ventilator-associated pneumonia and ventilator-induced diaphragmatic dysfunction). The latter strategy may also address the unavailability of enough ventilators to meet the increased demand of treating patients with COVID-19. Given that no randomized controlled trials are currently available to guide clinical practice regarding optimal timing of intubation, we propose a single-center randomized controlled feasibility trial to compare early intubation versus delayed intubation among patients with COVID-19 suffering from severe acute hypoxemic respiratory failure. The aim is that we gain experience and produce pilot data, which could inform the design of a subsequent large multi-center clinical trial.

Official Title
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Effect of Early versUs Delayed intubatiOn on Clinical Outcomes of Patients With COVID-19 (EUDOCO): a Feasibility Randomized Controlled Trial

Conditions
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COVID-19, Acute Hypoxemic Respiratory Failure

Intervention / Treatment
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* Other: Endotracheal intubation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with confirmed COVID-19 and severe acute hypoxemic respiratory failure Exclusion Criteria: Postoperative acute respiratory failure (within one week from surgery) After cardiac arrest Chronic hypoxemic respiratory failure Hypercapnic respiratory failure No full code Lack of equipoise of the clinical team Lack of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early intubation<br>Patients with COVID-19 suffering from severe acute hypoxemic respiratory failure (defined as the need for non-rebreather mask or high flow nasal oxygen with setting FiO2 of at least 90% or non-invasive mechanical ventilation to maintain a SpO2 >92%) for at least 48 hours will undergo intubation. | Other: Endotracheal intubation<br>* Endotracheal intubation<br>|
| Active Comparator: Delayed intubation<br>Patients with COVID-19 suffering from severe acute hypoxemic respiratory failure (defined as the need for non-rebreather mask or high flow nasal oxygen with setting FiO2 of at least 90% or non-invasive mechanical ventilation to maintain a SpO2 >92%) for at least 48 hours will continue to receive non-rebreather mask, high-flow nasal oxygen or non-invasive mechanical ventilation in an attempt to avoid intubation. | Other: Endotracheal intubation<br>* Endotracheal intubation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from onset of severe acute hypoxemic respiratory failure to intubation | Difference in time from onset of severe acute hypoxemic respiratory failure to intubation between the two groups will be the primary (feasibility) outcome | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ failure-free days | Number of days without the need for invasive mechanical ventilation, vasopressors and continuous renal replacement therapy with days after death not to be considered as organ failure-free days | 28 days | 
| Need for continuous renal replacement therapy |  | 28 days | 
| Ventilator-free days |  | 28 days | 
| ICU-free days | Intensive care unit-free days | 28 days | 
| Mortality | All-cause ICU-mortality | 28 days | 
| Number of severe post-intubation adverse events | Cardiac arrest and severe arterial desaturation (defined as SpO2 <80% for >5 minutes) | Within 30 minutes from intubation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19