Cerebral Oxygenation and Neurological Outcomes FOllowing CriticAL Illness-2 (CONFOCAL-2)

• ClinicalTrials.gov Identifier: NCT03141619
• Recruitment Status: Recruiting
• First Posted: May 5, 2017
• Last Update Posted: August 19, 2022
• Sponsor: Queen's University
• Collaborators: University Health Network, Toronto; Vancouver General Hospital; University of Western Ontario, Canada; University of Ottawa; Université de Montréal; University of Calgary; University of Pittsburgh
• Information provided by (Responsible Party): Dr. Gordon Boyd, Queen's University

Study Description

Brief Summary:

This study is designed to test the hypothesis that poor cerebral perfusion during critical illness is a risk factor for acute and long-term neurological dysfunction among survivors. We use near-infrared spectroscopy to measure brain tissue oxygenation as a non-invasive surrogate marker for cerebral perfusion. Acute neurological dysfunction is defined as the presence of delirium, which is assessed using the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). Chronic neurological dysfunction is defined as having quantitative impairments on robotic testing (KINARM robot) and traditional neuropsychological screening (Repeatable Battery for the Assessment of Neuropsychological Status).

Condition or disease
Critical Illness; Respiratory Failure; Shock; Delirium

Study Design

• Study Type: Observational
• Estimated Enrollment: 500 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Cerebral Oxygenation and Neurological Outcomes FOllowing CriticAL Illness-2
• Actual Study Start Date: October 13, 2017
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2025

Groups and Cohorts

Group/Cohort
Respiratory failure and/or shock; All enrolled patients will undergo 72 hours of monitoring of cerebral oxygenation with near-infrared spectroscopy.

Outcome Measures

Primary Outcome Measures :

1. Regional cerebral oxygenation (rSO2) and delirium [ Time Frame: 30 days ]
   Multivariate linear regression will be used to characterize the association between poor cerebral perfusion (as measured using duration of time (minutes) outside of MAPOPT, mean rSO2, and duration of disturbed cerebral autoregulation) and delirium severity to determine if poor cerebral perfusion is an independent predictor of delirium severity. We will estimate the unadjusted effect of each individual predictor on delirium severity (i.e., cumulative CAM-7 scores per patient). The simultaneous multivariate regression model will adjust for the following covariates (sex, a history of hypertension, a history of alcohol abuse, total sedative dose (in midazolam equivalents), total narcotic dose (fentanyl equivalents), severity of illness (APACHE II scores), pre-existing cognitive impairment (CDR score), length of ICU stay, and blood urea nitrogen. The multivariable model will provide the adjusted regression coefficients after controlling for all predictors included in the model.

Secondary Outcome Measures :

1. Assessment of secondary outcomes-physiological determinants of cerebral oxygenation [ Time Frame: 72 hours ]
   To assess the physiological determinants of rSO2, multiple linear regression will be performed using the patient average of each variable over the 72 hour data collection period. The following predictors will be included in the regression model: heart rate (HR), arterial oxygen saturation (SpO2), MAP, arterial blood gas data (i.e., pH, partial pressure of oxygen, and partial pressure of carbon dioxide), central venous oxygen saturation, and hemoglobin concentration (Hb). In addition, the multivariate model will control for the following covariates associated with cerebral perfusion: sex, age, as well as total sedative, narcotic, and vasopressor dosing. Simultaneous multiple linear regression with adjustment for all aforementioned covariates will be implemented. A within patient repeated measures analysis will also be performed by using the linear mixed effects model with 6 observations per subject reflecting each 12 hour period during the 72 hour data collection period.
2. Cerebral oxygenation as an independent risk factor for long-term cognitive impairment-RBANS [ Time Frame: 3 months and 12 months ]
   Multiple linear regression analysis will be used to assess if poor cerebral perfusion (i.e. time below MAPOPT, mean rSO2, duration of disturbed cerebral autoregulation) is associated with RBANS global cognition scores at 3- and 12-months post-ICU discharge. We will use the following clinical covariates collected on admission (i.e., pre-existing cognitive impairment, age, severity of illness) and data collected within the first 72 hours of the patients' ICU stay (i.e., narcotic dosing and benzodiazepine dosing). All covariates will be adjusted for in separate regression models for the cognitive outcomes at 3- and 12-months post-ICU discharge. If global cognition is significantly predicted by the impaired cerebral perfusion, we will conduct an exploratory analysis of the RBANS subdomains of cognition (i.e., delay and immediate memory, language, attention, visuospatial/constructional) adjusting for the aforementioned covariates to further explore specific domains of impairment.

Other Outcome Measures:

1. Time outside optimal MAP [ Time Frame: 72h, 3- and 12-months ]
   We define the optimal MAP as the MAP at which there is no statistically significant correlation between MAP and rSO2. The time outside the optimal MAP will be calculated, and will be assessed as an independent predictor of delirium, and 3- and 12-month cognitive outcomes.
2. Robotic quantification of neurological recovery [ Time Frame: 3 and 12 months ]
   A the Kingston site, participants will undergo additional neurological assessments with the KINARM robot and associated tasks. This data will be analyzed descriptively

Biospecimen Retention:   Samples Without DNA

Samples will be collected for proteomic assessments.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

We will be enrolling consecutive patients meeting eligibility criteria from each site in this multi-centred study.

Criteria

Inclusion

1. Adults ≥ 18 years old

2. Admitted to a critical care unit requiring one or more of the following:

   (a) Respiratory failure requiring invasive mechanical ventilation with an expected duration >24 hours (b) Shock of any etiology. Shock is defined by the need for one of the following vasopressors/inotropes: (i) Dopamine ≥7.5 mcg/kg/min (ii) Dobutamine ≥5 mcg/kg/min (iii) Norepinephrine ≥5 mcg/min (iv) Phenylephrine ≥75 mcg/min (v) Epinephrine at any dose (vi) Milrinone at any dose (if used in conjunction with another agent) (vii) Vasopressin ≥0.03 u/min(if used in conjunction with another agent)

Exclusion:

1. Admission to the ICU > 24 hours
2. Life expectancy <24 hours
3. Admitting diagnosis that affects the central nervous system
4. Any reason that the subject may not be able to participate in the follow up assessments (i.e. limb amputation, paresis, neuromuscular disorders)

Contacts and Locations

Contacts

Contact: J. Gordon Boyd, MD, PhD; 613-549-6666 ext 6228; boydj@kgh.kari.net

Contact: Miranda Hunt; 613-549-6666; huntm4@KGH.KARI.NET

Locations

Canada, Ontario

Kingston General Hospital; Recruiting

Kingston, Ontario, Canada, K7L3V7

Contact: John G Boyd, MD, PhD 613-549-6666 ext 6228 2jgb1@queensu.ca

Sponsors and Collaborators

Queen's University

University Health Network, Toronto

Vancouver General Hospital

University of Western Ontario, Canada

University of Ottawa

Université de Montréal

University of Calgary

University of Pittsburgh

Investigators

• Principal Investigator: J. Gordon Boyd, MD, PhD; Queen's University

More Information

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

Khan JM, Wood MD, Lee KFH, Maslove D, Muscedere J, English SW, Ball I, Slessarev M, Boyd JG. Delirium, Cerebral Perfusion, and High-Frequency Vital-Sign Monitoring in the Critically Ill. The CONFOCAL-2 Feasibility Study. Ann Am Thorac Soc. 2021 Jan;18(1):112-121. doi: 10.1513/AnnalsATS.202002-093OC. Erratum In: Ann Am Thorac Soc. 2021 Feb;18(2):378.

Wood MD, Khan J, Lee KFH, Maslove DM, Muscedere J, Hunt M, Scott SH, Day A, Jacobson JA, Ball I, Slessarev M, O'Regan N, English SW, McCredie V, Chasse M, Griesdale D, Boyd JG. Assessing the relationship between near-infrared spectroscopy-derived regional cerebral oxygenation and neurological dysfunction in critically ill adults: a prospective observational multicentre protocol, on behalf of the Canadian Critical Care Trials Group. BMJ Open. 2019 Jun 25;9(6):e029189. doi: 10.1136/bmjopen-2019-029189.

• Responsible Party: Dr. Gordon Boyd, Assistant Professor, Queen's University
• ClinicalTrials.gov Identifier: NCT03141619
• Other Study ID Numbers: CTO Project ID 0815
• First Posted: May 5, 2017
• Last Update Posted: August 19, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Dr. Gordon Boyd, Queen's University:

cerebral oximetry; near-infrared spectroscopy; neurocognitive; post-ICU syndrome

Additional relevant MeSH terms:

Respiratory Insufficiency; Critical Illness; Respiration Disorders; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes