Respiratory FailurePILOTNCT03537937
Pragmatic Investigation of optimaL Oxygen Targets Trial
A study testing Lower SpO2 Target, Intermediate SpO2 Target and Higher SpO2 Target in people with Respiratory Failure, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure
- What is being tested?
- Lower SpO2 Target, Intermediate SpO2 Target and Higher SpO2 Target
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,541 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2018to 31 Jan 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: 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.
- Conditions
- Respiratory Failure
- Being tested
- Lower SpO2 Target, Intermediate SpO2 Target, Higher SpO2 Target
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lower SpO2 TargetOther
SpO2 target 90% (range 88-92%)
Intermediate SpO2 TargetOther
SpO2 target 94% (range 92-96%)
Higher SpO2 TargetOther
SpO2 target 98% (range 96-100%)
| Study group | Role | What they receive |
|---|---|---|
| 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%). Receives: 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%). Receives: 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%). Receives: Other: Higher SpO2 Target |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (7)
28-day, In-hospital Mortality (Secondary Outcome)
All-cause mortality prior to discharge from the hospital, assessed at 28 days after enrollment (Secondary Outcome).
Measured: 28 days
Intensive Care Unit Mortality (Exploratory Clinical Outcome)
All-cause mortality prior to transfer out of the intensive care unit
Measured: 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.
Measured: 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
Measured: 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
Measured: 28 days
Hospital-free Days (Exploratory Clinical Outcome)
Number of days alive and free from hospital admission to study day 28
Measured: 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
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start1 Jul 2018
- Primary completion31 Jan 2022
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,541 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew Semler, Vanderbilt University Medical Center
- Investigators
- Matthew W Semler, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537937
- Sponsor's protocol ID
- 171272
- Acronym
- PILOT
- Status last verified
- Nov 2022
- First submitted
- 15 May 2018
- Last updated
- 25 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39784122Semler 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.
PubMed 36278971Semler 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.
PubMed 34711597
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Investigation of optimaL Oxygen Targets (PILOT) Trial
- ClinicalTrials.gov ID
- NCT03537937
- Acronym / sponsor ID
- PILOT / 171272
- Conditions
- Respiratory Failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,541 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Posted 25 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| Lower SpO2 Target | Active comparator | Other: Lower SpO2 TargetDuring 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%). |
| Intermediate SpO2 Target | Active comparator | Other: Intermediate SpO2 TargetDuring 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%). |
| Higher SpO2 Target | Active comparator | Other: Higher SpO2 TargetDuring 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%). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lower SpO2 TargetSpO2 target 90% (range 88-92%) | Other | Lower SpO2 Target |
| Intermediate SpO2 TargetSpO2 target 94% (range 92-96%) | Other | Intermediate SpO2 Target |
| Higher SpO2 TargetSpO2 target 98% (range 96-100%) | Other | Higher SpO2 Target |
Primary outcome
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.
7 secondary outcomes
28-day, In-hospital Mortality (Secondary Outcome)
Time frame: 28 days
Intensive Care Unit Mortality (Exploratory Clinical Outcome)
Time frame: 28 days
Vasopressor-free Days (Exploratory Clinical Outcome)
Time frame: 28 days
Renal Replacement Therapy-free Days (Exploratory Clinical Outcome)
Time frame: 28 days
Intensive Care Unit-free Days (Exploratory Clinical Outcome)
Time frame: 28 days
Hospital-free Days (Exploratory Clinical Outcome)
Time frame: 28 days
Acute Kidney Injury (AKI) (Exploratory Organ Function Outcome)
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39784122Shapiro 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.
- Derived from this study: PubMed 36278971Semler 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.
- Derived from this study: PubMed 34711597Semler 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew W Semler, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lower SpO2 Target, Intermediate SpO2 Target and Higher SpO2 Target in people with Respiratory Failure, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator-free Days (VFDs) to Study Day 28 (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03537937, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2023.