Pragmatic Investigation of optimaL Oxygen Targets Trial

Study Overview
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Brief Summary
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Mechanical ventilation of ICU patients universally involves titration of the fraction of inspired oxygen (FiO2) to maintain arterial oxygen saturation (SpO2). Despite decades of ICU practice, however, the optimal SpO2 target remains unknown. Current guidelines offer divergent recommendations as to the optimal SpO2 target. Therefore, we propose a 2,250-patient cluster-randomized cluster-crossover trial comparing a lower SpO2 target (90%; range 88-92%), an intermediate SpO2 target (94%; range 92-96%), and a higher SpO2 target (98%; range 96-100%) with regard to the outcome of days alive and free of invasive mechanical ventilation.

Official Title
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Pragmatic Investigation of optimaL Oxygen Targets (PILOT) Trial

Conditions
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Respiratory Failure

Intervention / Treatment
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* Other: Lower SpO2 Target
* Other: Intermediate SpO2 Target
* Other: Higher SpO2 Target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Receiving mechanical ventilation through an endotracheal tube or tracheostomy Admitted to the study ICU or admission to the study ICU from the emergency department is planned Exclusion Criteria: Known pregnancy or beta hCG level greater than the laboratory upper limit of normal in a patient capable of becoming pregnant Known to be a prisoner

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: Crossover Assignment
Interventional Model Description: In the PILOT trial, the entire study ICU will be assigned to a single SpO2 target (cluster-randomized) and the ICU will switch between lower, intermediate, and higher SpO2 targets every two months in a randomly generated sequence (cluster-crossover).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lower SpO2 Target<br>During invasive mechanical ventilation in a study location, the fraction of inspired oxygen will be titrated to target an arterial oxygen saturation of 90% (range 88-92%). | Other: Lower SpO2 Target<br>* SpO2 target 90% (range 88-92%)<br>|
| Active Comparator: Intermediate SpO2 Target<br>During invasive mechanical ventilation in a study location, the fraction of inspired oxygen will be titrated to target an arterial oxygen saturation of 94% (range 92-96%). | Other: Intermediate SpO2 Target<br>* SpO2 target 94% (range 92-96%)<br>|
| Active Comparator: Higher SpO2 Target<br>During invasive mechanical ventilation in a study location, the fraction of inspired oxygen will be titrated to target an arterial oxygen saturation of 98% (range 96-100%). | Other: Higher SpO2 Target<br>* SpO2 target 98% (range 96-100%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free Days (VFDs) to Study Day 28 | Number of days alive and free from invasive mechanical ventilation between the final liberation from invasive mechanical ventilation before 28 days and study day 28. Patients who continue to receive invasive mechanical ventilation at day 28 or have died prior to day 28 will receive zero VFDs. For patients who return to invasive mechanical ventilation and are subsequently liberated from invasive mechanical ventilation prior to day 28, VFDs will be counted from final liberation from mechanical ventilation. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day, In-hospital Mortality (Secondary Outcome) | All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment (Secondary Outcome). | 28 days | 
| Intensive Care Unit Mortality (Exploratory Clinical Outcome) | All-cause mortality prior to transfer out of the intensive care unit | 28 days | 
| Vasopressor-free Days (Exploratory Clinical Outcome) | Number of days alive and free from vasopressor receipt between the final receipt of vasopressors before 28 days and study day 28. | 28 days | 
| Renal Replacement Therapy-free Days (Exploratory Clinical Outcome) | Number of days alive and free from renal replacement therapy between the final receipt of renal replacement therapy before 28 days and study day 28 | 28 days | 
| Intensive Care Unit-free Days (Exploratory Clinical Outcome) | Number of days alive and free from intensive care unit admission after the final transfer out of the intensive care unit before 28 days to study day 28 | 28 days | 
| Hospital-free Days (Exploratory Clinical Outcome) | Number of days alive and free from hospital admission to study day 28 | 28 days | 
| Acute Kidney Injury (AKI) (Exploratory Organ Function Outcome) | Presence of Stage II or greater AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria | 28 days |