Pragmatic Investigation of optimaL Oxygen Targets Trial (PILOT)

• ClinicalTrials.gov Identifier: NCT03537937
• Recruitment Status: Completed
• First Posted: May 25, 2018
• Last Update Posted: May 23, 2022
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): Matthew Semler, Vanderbilt University Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Respiratory Failure	Other: Lower SpO2 Target; Other: Intermediate SpO2 Target; Other: Higher SpO2 Target	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2541 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention 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 (Outcomes Assessor)
• Masking Description: Observer bias will be minimized by use of objective endpoints collected in duplicate by [1] study personnel blinded to group assignment and [2] automated data extraction from the electronic health record.
• Primary Purpose: Treatment
• Official Title: Pragmatic Investigation of optimaL Oxygen Targets (PILOT) Trial
• Actual Study Start Date: July 1, 2018
• Actual Primary Completion Date: January 31, 2022
• Actual Study Completion Date: January 31, 2022

Arms and Interventions

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%)

Outcome Measures

Primary Outcome Measures :

1. Ventilator-free days (VFDs) to study day 28 [ Time Frame: 28 days ]
   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.

Secondary Outcome Measures :

1. 28-day, in-hospital Mortality (Secondary Outcome) [ Time Frame: 28 days ]
   All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment (Secondary Outcome).
2. Intensive Care Unit Mortality (Exploratory Clinical Outcome) [ Time Frame: 28 days ]
   All-cause mortality prior to transfer out of the intensive care unit
3. Vasopressor-free days (Exploratory Clinical Outcome) [ Time Frame: 28 days ]
   Number of days alive and free from vasopressor receipt between the final receipt of vasopressors before 28 days and study day 28.
4. Renal replacement therapy-free days (Exploratory Clinical Outcome) [ Time Frame: 28 days ]
   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
5. Intensive care unit-free days (Exploratory Clinical Outcome) [ Time Frame: 28 days ]
   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
6. Hospital-free days (Exploratory Clinical Outcome) [ Time Frame: 28 days ]
   Number of days alive and free from hospital admission to study day 28
7. Daily non-respiratory Sequential Organ Failure Assessment (SOFA) Score (Exploratory Organ Function Outcome) [ Time Frame: 28 days ]
   The Sequential Organ Failure Assessment (SOFA) score (Vincent et al Critical Care Medicine 1998) is composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction or failure. Scores range from 0 (no evidence of organ dysfunction or failure) to 24 (evidence of severe dysfunction failure in each of the six organ systems). The modified non-respiratory SOFA score is composed of scores from five of the six organ systems included in the complete SOFA score (excluding the respiratory system), graded on the same scale as the complete SOFA score. Scores range from 0 (no evidence of organ dysfunction or failure) to 20 (evidence of severe organ dysfunction or failure in each of the five organ systems assessed).
8. Plasma creatinine (Exploratory Organ Function Outcome) [ Time Frame: 28 days ]
   Daily plasma creatinine value (mg/dL)
9. Plasma lactate (Exploratory Organ Function Outcome) [ Time Frame: 28 days ]
   Daily plasma lactate value (mmol/L)
10. Acute respiratory distress syndrome (ARDS) (Exploratory Organ Function Outcome) [ Time Frame: 28 days ]
    Presence of ARDS by Berlin Criteria
11. Acute Kidney Injury (AKI) (Exploratory Organ Function Outcome) [ Time Frame: 28 days ]
    Presence of Stage II or greater AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria

Other Outcome Measures:

1. Atrial arrhythmia (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   Documented atrial arrhythmia
2. Ventricular arrhythmia (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   Documented ventricular arrhythmia
3. Cardiac arrest (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   Cardiac arrest with return of spontaneous circulation
4. Pneumothorax or pneumomediastinum (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   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.
5. Ischemic stroke (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   New ischemic stroke between enrollment and 28 days after enrollment as diagnosed by computed tomography, magnetic resonance imaging, or cerebral angiography.
6. Myocardial infarction (Exploratory Safety Outcome) [ Time Frame: 28 days ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Matthew Semler, Assistant Professor of Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT03537937
• Other Study ID Numbers: 171272
• First Posted: May 25, 2018
• Last Update Posted: May 23, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases