The Effect of Non-invasive Respiratory Support on Outcome and Its Risks in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2)-Related Hypoxemic Respiratory Failure

Study Overview
=================
Brief Summary
-----------------
Coronavirus disease (COVID-19) can result in severe hypoxemic respiratory failure that ultimately may require invasive mechanical ventilation in the Intensive Care Unit (ICU). Although lifesaving, invasive mechanical ventilation is associated with high mortality, severe discomfort for patient, long-term sequelae, stress to loved-ones and high costs for society. During the ongoing pandemic high number of invasively ventilated COVID-19 patients overwhelmed ICU capacity. Non-invasive respiratory support, such as high flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) have the potential to reduce the risk for invasive mechanical ventilation and in selected cases ICU admission. However, data from different studies are conflicting and studies performed in COVID-19 patients are of limited quality. Furthermore, identification of early predictors of HFNO/NIV treatment failure may prevent unnecessary delay of initiation of invasive ventilation, which may be associated with adverse clinical outcome. The development and validation of a prediction model, that incorporates readily available clinically data may prove pivotal to fine-tune non-invasive respiratory support. The overall aim of the NORMO2 project is to investigate the role and risks of HFNO and NIV to improve outcome in hospitalized hypoxemic COVID-19 patients.

Official Title
-----------------
The Effect of Non-invasive Respiratory Support on Outcome and Its Risks in SARS-COV-2-related Hypoxemic Respiratory Failure

Conditions
-----------------
COVID-19, Hypoxemic Respiratory Failure

Intervention / Treatment
-----------------
* Device: High flow nasal oxygen (HFNO, more than 15 L/min)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sars-Cov-2 infection hospital admission (emergency department, inpatient or ICU) hypoxemic respiratory failure, defined as P/F ratio below or including 200 Exclusion Criteria: hypercapnia (PCO2 > 45 mmHG in combination with acidemia (pH < 7.35)) pregnancy do not resuscitate order

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Full analysis<br>All eligible patients. | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|
| P/F ratio subgroups<br>Patients with a P/F ratio split in groups of <=100; 100-150; 150-200 | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|
| Respiratory rate subgroups<br>Patients with a respiratory rate split in groups of <=25; >25 breaths/min | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|
| Body mass index (BMI) subgroups<br>Patients with BMI split in groups of <=25; 25-30; 30-35; >35 kg/m^2 | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|
| Immunocompromised subgroups<br>Immunocompromised patients due to medication or an underlined condition. | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|
| Intensive care unit (ICU) subgroup<br>Only patients eligible within 24 hours of ICU admission. | Device: High flow nasal oxygen (HFNO, more than 15 L/min)<br>* Non-invasive respiratory support strategy<br>* Other names: Conventional oxygen (COT, between 10 - 15 L/min);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients requiring invasive mechanical ventilation |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at day 30 |  | 30 days | 
| ICU-free days |  | 30 days |