# Cognitive Outcomes in the Pragmatic Investigation of Optimal Oxygen Targets (CO-PILOT) Trial

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $212,500

## Abstract

PROJECT SUMMARY
Based upon our previous work, one out of four intensive care unit (ICU) survivors will acquire cognitive
impairment similar to Alzheimer’s disease and related dementias (ADRD) at 12-months. This leads to reduced
employment, decreased quality of life, and loss of independence. This growing public health problem
especially affects the 2 to 3 million ICU patients who are mechanically ventilated each year. Currently,
mechanical ventilation of critically ill adults universally involves titration of the fraction of inspired oxygen (FiO2)
to maintain arterial oxygen saturation (SpO2). The optimal SpO2 target, however, remains unknown; current
recommendations range from tolerating SpO2 values as low as 88% (Acute Respiratory Distress Syndrome
Network) to pursuing SpO2 values as high as 98% (British Thoracic Society). Because hypoxia is strongly
implicated in ADRD pathogenesis, we hypothesize that targeting lower SpO2 during mechanical ventilation is
significantly associated with worse long-term global cognition compared with higher SpO2 targets. To address
this hypothesis, we propose this ancillary study to the NIH-funded Pragmatic Investigation of optimaL Oxygen
Targets (PILOT) trial. The PILOT parent trial is a cluster-randomized, cluster-crossover trial comparing low
(88% to 92%), intermediate (93% to 96%), and high (>96%) SpO2 targets during mechanical ventilation and
will enroll 2,250 patients from the medical ICU over a three-year period. PILOT’s outcomes are ventilator-free
days and mortality but is not assessing long-term global cognition. Therefore, we propose this ancillary study
titled Cognitive Outcomes in PILOT (CO-PILOT) which has the following specific aims: (1) determine if the
lower SpO2 target (88 to 92%) is significantly associated with worse 6-month global cognition compared with
higher (>92%) SpO2 targets in mechanically ventilated ICU patients; and (2) determine how low SpO2 targets
(88-92%) affects individual cognitive domains, particularly immediate and delayed memory, at 6-months
compared with higher (>92%) SpO2 targets among mechanically ventilated ICU patients. CO-PILOT will enroll
a subset of 189 survivors who are enrolled in PILOT over an 18-month period. This R21 will provide the
funding and resources needed to obtain 6-month cognitive and secondary outcome measurements. Six-month
global cognition and its individual cognitive domains (intermediate and delayed memory, attention, visuospatial
construction, and language) will be determined by face-to-face neuropsychological testing using the
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). It is possible that the PILOT
parent trial may report that a lower SpO2 target improves survival, but the CO-PILOT ancillary trial may reveal
that this will come at the expense of long-term cognition. Because patients and their families likely have
different preferences for what they consider the ideal outcome is, both studies are necessary to provid...

## Key facts

- **NIH application ID:** 10077810
- **Project number:** 5R21AG063126-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jin Ho Han
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $212,500
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077810

## Citation

> US National Institutes of Health, RePORTER application 10077810, Cognitive Outcomes in the Pragmatic Investigation of Optimal Oxygen Targets (CO-PILOT) Trial (5R21AG063126-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10077810. Licensed CC0.

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