Trial Outcomes & Findings for Pragmatic Investigation of optimaL Oxygen Targets Trial (NCT NCT03537937)

NCT ID: NCT03537937

Last Updated: 2023-09-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 2541 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2023-09-25

Participant Flow

Participant milestones

Measure	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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Overall Study STARTED	808	859	874
Overall Study COMPLETED	808	859	874
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pragmatic Investigation of optimaL Oxygen Targets Trial

Baseline characteristics by cohort

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)	Total n=2541 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	59 years n=7 Participants	59 years n=5 Participants	58 years n=4 Participants
Sex: Female, Male Female	361 Participants n=5 Participants	385 Participants n=7 Participants	409 Participants n=5 Participants	1155 Participants n=4 Participants
Sex: Female, Male Male	447 Participants n=5 Participants	474 Participants n=7 Participants	465 Participants n=5 Participants	1386 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	28 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	121 Participants n=5 Participants	140 Participants n=7 Participants	136 Participants n=5 Participants	397 Participants n=4 Participants
Race (NIH/OMB) White	649 Participants n=5 Participants	666 Participants n=7 Participants	695 Participants n=5 Participants	2010 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	28 Participants n=5 Participants	38 Participants n=7 Participants	34 Participants n=5 Participants	100 Participants n=4 Participants
Overall Number of Participants	808 Participants n=5 Participants	859 Participants n=7 Participants	874 Participants n=5 Participants	2541 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Ventilator-free Days (VFDs) to Study Day 28	20 number of days Interval 0.0 to 25.0	21 number of days Interval 0.0 to 25.0	21 number of days Interval 0.0 to 26.0

SECONDARY outcome

Timeframe: 28 days

All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment (Secondary Outcome).

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
28-day, In-hospital Mortality (Secondary Outcome)	281 Participants	292 Participants	290 Participants

SECONDARY outcome

Timeframe: 28 days

All-cause mortality prior to transfer out of the intensive care unit

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Intensive Care Unit Mortality (Exploratory Clinical Outcome)	244 Participants	259 Participants	249 Participants

SECONDARY outcome

Timeframe: 28 days

Number of days alive and free from vasopressor receipt between the final receipt of vasopressors before 28 days and study day 28.

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Vasopressor-free Days (Exploratory Clinical Outcome)	25 number of days Interval 0.0 to 28.0	25 number of days Interval 0.0 to 28.0	25 number of days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Renal Replacement Therapy-free Days (Exploratory Clinical Outcome)	28 number of days Interval 0.0 to 28.0	28 number of days Interval 0.0 to 28.0	0 number of days Interval 0.0 to 28.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Intensive Care Unit-free Days (Exploratory Clinical Outcome)	20 number of days Interval 0.0 to 24.0	19 number of days Interval 0.0 to 24.0	20 number of days Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: 28 days

Number of days alive and free from hospital admission to study day 28

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Hospital-free Days (Exploratory Clinical Outcome)	10 number of days Interval 0.0 to 20.0	10 number of days Interval 0.0 to 21.0	10 number of days Interval 0.0 to 20.0

SECONDARY outcome

Timeframe: 28 days

Presence of Stage II or greater AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Acute Kidney Injury (AKI) (Exploratory Organ Function Outcome)	230 Participants	253 Participants	251 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Documented atrial arrhythmia

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Atrial Arrhythmia (Exploratory Safety Outcome)	64 Participants	100 Participants	95 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Documented ventricular arrhythmia

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Ventricular Arrhythmia (Exploratory Safety Outcome)	20 Participants	21 Participants	20 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Cardiac arrest with return of spontaneous circulation

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Cardiac Arrest (Exploratory Safety Outcome)	26 Participants	26 Participants	31 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Pneumothorax or Pneumomediastinum (Exploratory Safety Outcome)	17 Participants	24 Participants	36 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

New ischemic stroke between enrollment and 28 days after enrollment as diagnosed by computed tomography, magnetic resonance imaging, or cerebral angiography.

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Ischemic Stroke (Exploratory Safety Outcome)	12 Participants	17 Participants	16 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Lower SpO2 Target n=808 Participants 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 Participants 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 Participants 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Myocardial Infarction (Exploratory Safety Outcome)	16 Participants	28 Participants	14 Participants

Adverse Events

Lower SpO2 Target

Serious events: 0 serious events

Other events: 1 other events

Deaths: 285 deaths

Intermediate SpO2 Target

Serious events: 0 serious events

Other events: 0 other events

Deaths: 296 deaths

Higher SpO2 Target

Serious events: 0 serious events

Other events: 0 other events

Deaths: 297 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lower SpO2 Target n=808 participants at risk 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%). Lower SpO2 Target: SpO2 target 90% (range 88-92%)	Intermediate SpO2 Target n=859 participants at risk 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%). Intermediate SpO2 Target: SpO2 target 94% (range 92-96%)	Higher SpO2 Target n=874 participants at risk 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%). Higher SpO2 Target: SpO2 target 98% (range 96-100%)
Cardiac disorders Relative bradycardia	0.12% 1/808 • Number of events 1 • enrollment to day 28	0.00% 0/859 • enrollment to day 28	0.00% 0/874 • enrollment to day 28

Additional Information

Chair of the Steering Committee

Pragmatic Critical Care Research Group

Phone: (615) 322-3412

Email: matthew.w.semler@vumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place