Cerebral Oxygenation and Neurological Outcomes FOllowing CriticAL Illness-2

Critical Illness Clinical Trial

— CONFOCAL-2  

Official title:

Cerebral Oxygenation and Neurological Outcomes FOllowing CriticAL Illness-2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03141619
• Other study ID #: CTO Project ID 0815
• Status: Recruiting
• Start date: October 13, 2017
• Est. completion date: June 2025

Study information

• Verified date: December 2023
• Source: Queen's University
• Contact: J. Gordon Boyd, MD, PhD
• Phone: 613-549-6666
• Email: boydj[@]kgh.kari.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Critical Illness
• Delirium
• Respiratory Failure
• Respiratory Insufficiency
• Shock

Locations

Country	Name	City	State
Canada	Kingston General Hospital	Kingston	Ontario

Sponsors (8)

Lead Sponsor	Collaborator
Dr. Gordon Boyd	Université de Montréal, University Health Network, Toronto, University of Calgary, University of Ottawa, University of Pittsburgh, Vancouver General Hospital, Western University, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time outside optimal MAP	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.	72h, 3- and 12-months
Other	Robotic quantification of neurological recovery	A the Kingston site, participants will undergo additional neurological assessments with the KINARM robot and associated tasks. This data will be analyzed descriptively	3 and 12 months
Primary	Regional cerebral oxygenation (rSO2) and delirium	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.	30 days
Secondary	Assessment of secondary outcomes-physiological determinants of cerebral oxygenation	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.	72 hours
Secondary	Cerebral oxygenation as an independent risk factor for long-term cognitive impairment-RBANS	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.	3 months and 12 months