Pragmatic Investigation of optimaL Oxygen Targets Trial (PILOT)

Pragmatic Investigation of optimaL Oxygen Targets (PILOT) Trial

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure
• Intervention / Treatment: Other: Lower SpO2 Target; Other: Intermediate SpO2 Target; Other: Higher SpO2 Target

• Study Type: Interventional
• Enrollment (Actual): 2541
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Receiving mechanical ventilation through an endotracheal tube or tracheostomy
3. Admitted to the study ICU or admission to the study ICU from the emergency department is planned

Exclusion Criteria:

1. Known pregnancy or beta hCG level greater than the laboratory upper limit of normal in a patient capable of becoming pregnant
2. Known to be a prisoner

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lower SpO2 Target; 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; SpO2 target 90% (range 88-92%)
Active Comparator: Intermediate SpO2 Target; 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; SpO2 target 94% (range 92-96%)
Active Comparator: Higher SpO2 Target; 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; SpO2 target 98% (range 96-100%)

What is the study measuring?

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
Intensive Care Unit Mortality (Exploratory Clinical Outcome)	All-cause mortality prior to transfer out of the intensive care unit	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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial Arrhythmia (Exploratory Safety Outcome)	Documented atrial arrhythmia	28 days
Ventricular Arrhythmia (Exploratory Safety Outcome)	Documented ventricular arrhythmia	28 days
Cardiac Arrest (Exploratory Safety Outcome)	Cardiac arrest with return of spontaneous circulation	28 days
Pneumothorax or Pneumomediastinum (Exploratory Safety Outcome)	Pneumothorax or pneumomediastinum as defined by documentation in the electronic health record by treating clinicians or radiology of a pneumothorax on thoracic imaging or thoracic ultrasound.	28 days
Ischemic Stroke (Exploratory Safety Outcome)	New ischemic stroke between enrollment and 28 days after enrollment as diagnosed by computed tomography, magnetic resonance imaging, or cerebral angiography.	28 days
Myocardial Infarction (Exploratory Safety Outcome)	New myocardial infarction between enrollment and 28 days after enrollment, defined as detection of a rise in cardiac troponin values with at least one value above the 99th percentile and clinical evidence of acute myocardial ischemia.	28 days

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Matthew W Semler, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Semler MW, Casey JD, Lloyd BD, Hastings PG, Hays MA, Stollings JL, Buell KG, Brems JH, Qian ET, Seitz KP, Wang L, Lindsell CJ, Freundlich RE, Wanderer JP, Han JH, Bernard GR, Self WH, Rice TW; PILOT Investigators and the Pragmatic Critical Care Research Group. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Engl J Med. 2022 Nov 10;387(19):1759-1769. doi: 10.1056/NEJMoa2208415. Epub 2022 Oct 24.
• Semler MW, Casey JD, Lloyd BD, Hastings PG, Hays M, Roth M, Stollings J, Brems J, Buell KG, Wang L, Lindsell CJ, Freundlich RE, Wanderer JP, Bernard GR, Self WH, Rice TW; PILOT Investigators and the Pragmatic Critical Care Research Group. Protocol and statistical analysis plan for the Pragmatic Investigation of optimaL Oxygen Targets (PILOT) clinical trial. BMJ Open. 2021 Oct 28;11(10):e052013. doi: 10.1136/bmjopen-2021-052013.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: May 15, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 25, 2018

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: November 11, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: 171272

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The NIH's guidelines for data sharing will serve as the model for the approach we will follow for the proposed investigation;

http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm

Even though the final dataset will be stripped of identifiers prior to release for sharing, the inherent link between the period in which the patient was admitted to the study ICU and group assignment in a cluster-crossover trial introduces a significant risk for deductive disclosure of subjects. Thus, we will make the data and associated documentation available to users only under a data sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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