Pragmatic Investigation of optimaL Oxygen Targets Trial

NCT03537937 | Completed Results DMC

• 1 other identifier: 171272
• Study Type: interventional
• Target: 2,541
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 28-day, In-hospital Mortality (Secondary Outcome)

  28 days

• Intensive Care Unit Mortality (Exploratory Clinical Outcome)

  28 days

• Vasopressor-free Days (Exploratory Clinical Outcome)

  28 days

• Renal Replacement Therapy-free Days (Exploratory Clinical Outcome)

  28 days

• Intensive Care Unit-free Days (Exploratory Clinical Outcome)

  28 days

Other Outcomes (6)

• Atrial Arrhythmia (Exploratory Safety Outcome)

  28 days

• Ventricular Arrhythmia (Exploratory Safety Outcome)

  28 days

• Cardiac Arrest (Exploratory Safety Outcome)

  28 days

Study Arms (3)

Lower SpO2 Target

ACTIVE COMPARATOR

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

Intermediate SpO2 Target

ACTIVE COMPARATOR

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

Higher SpO2 Target

ACTIVE COMPARATOR

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

Interventions

Lower SpO2 Target OTHER

SpO2 target 90% (range 88-92%)

Lower SpO2 Target

Intermediate SpO2 Target OTHER

SpO2 target 94% (range 92-96%)

Intermediate SpO2 Target

Higher SpO2 Target OTHER

SpO2 target 98% (range 96-100%)

Higher SpO2 Target

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Shapiro JC, Casey JD, Qian ET, Seitz KP, Wang L, Lloyd BD, Stollings JL, Freundlich RE, Self WH, Rice TW, Wanderer JP, Semler MW; Pragmatic Critical Care Research Group. Oxygen Targets for Mechanically Ventilated Adults with Sepsis: Secondary Analysis of the PILOT Trial. J Intensive Care Med. 2025 May;40(5):486-494. doi: 10.1177/08850666241299378. Epub 2025 Jan 9.

  PMID: 39784122 DERIVED

• 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.

  PMID: 36278971 DERIVED

• 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.

  PMID: 34711597 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Results Point of Contact

• Title: Chair of the Steering Committee
• Organization: Pragmatic Critical Care Research Group

matthew.w.semler@vumc.org

(615) 322-3412

Study Officials

• Matthew W Semler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: 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).

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: May 25, 2018
• Study Start: July 1, 2018
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2022
• Last Updated: September 25, 2023
• Results First Posted: September 25, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE

Locations

US (1)