Neurocognitive Outcomes for ICU Patients With Acute Kidney Injury (INCOGNITOAKI)

Identifying Neurocognitive Outcomes and Cerebral Oxygenation in Critically Ill Adults on Acute Kidney Replacement Therapy in the Intensive Care Unit

Introduction. Initiation of acute kidney replacement therapy (KRT) is common in critically ill adults admitted to the intensive care unit (ICU), and is associated with increased morbidity and mortality. KRT has been linked to poor neurocognitive outcomes, leading to a reduced quality of life, as well as increased utilization of healthcare resources. Adults initiated on dialysis in the ICU may be particularly at risk of neurocognitive impairment, as survivors of critical illness are already predisposed to developing cerebrovascular disease and cognitive dysfunction over the long-term relative to healthy controls. Regional cerebral oxygen saturation (rSO2) may provide a critical early marker of long-term neurocognitive impairment in patients in this population. The INCOGNITO-AKI study aims to understand cerebral oxygenation in patients undergoing KRT, either continuous or intermittent, in the ICU. These findings will be correlated with long-term cognitive and functional outcomes, as well as structural brain pathology.

Methods and analysis. 108 patients scheduled to undergo treatment for acute kidney injury with KRT in the Kingston Health Sciences Centre ICU will be recruited into this prospective observational study. Enrolled patients will be assessed with intradialytic cerebral oximetry using near infrared spectroscopy (NIRS). Delirium will be assessed daily with the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) and delirium severity quantified as cumulative CAM-ICU-7 scores. Neurocognitive impairment will be assessed at 3- and 12-months after hospital discharge using the Kinarm and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Structural brain pathology on MRI will also be measured at the same timepoints. Driving safety, adverse events, and medication adherence will be assessed at 12-months to evaluate the impact of neurocognitive impairment on functional outcomes.

Ethics and dissemination. This study has been approved by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (Approval number: DMED-2424-20). Results will be presented at critical care scientific conferences and a lay summary will be provided to patients and families in their preferred format.

Study Overview

• Status: Recruiting
• Conditions: Delirium; Critical Illness; Cognitive Impairment; Acute Kidney Injury; Cerebral Oxygenation; Cerebral Autoregulation
• Intervention / Treatment: Diagnostic test: Cerebral oxygenation

• Study Type: Observational
• Enrollment (Estimated): 104

Contacts and Locations

• Study Contact: Name: J. Gordon Boyd, MD, PhD; Phone Number: 6228 613-549-6666; Email: gordon.boyd@kingstonhsc.ca
• Study Contact Backup: Name: Tasha Jawa, MSc; Phone Number: 416-627-1508; Email: tasha.jawa@queensu.ca

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L3C9
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: J G Boyd, MD, PhD; Phone Number: 6135392754; Email: gordon.boyd@kingstonhsc.ca
      • Contact: Tasha Jawa, MSc.; Phone Number: 416-627-1508; Email: tasha.jawa@queensu.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from the Kingston Health Sciences Centre Intensive Care Unit (ICU), which is a 33-bed medical/surgical/trauma/neurological ICU. Patients admitted to the ICU generally require invasive mechanical ventilation for respiratory failure and/or vasoactive medications for hemodynamic support.

Description

Inclusion Criteria:

• age greater than or equal to 18 years
• admitted to the Kingston Health Sciences Intensive Care Unit
• diagnosis of severe AKI requiring Kidney Replacement Therapy (KRT) (defined by the presence of either a twofold increase in serum creatinine from baseline, serum creatinine level greater than or equal to 354 micromol/L with an increase of 27 micromol/L from baseline, or urine output <6 mL/kg in the preceding 12 hours)
• within 12 hours of initiation of KRT via intermittent hemodialysis (iHD) or continuous kidney replacement therapy (CKRT).

Exclusion Criteria:

• acquired or congenital neurological disorders
• any contraindication to testing with cerebral oximetry, Kinarm, or MRI (e.g., claustrophobia, limb amputation, paresis, neuromuscular disorders, etc.)
• KRT via PD
• failure to consent
• life expectancy less than 24 hours
• clinical suspicion of renal obstruction
• rapidly progressive glomerulonephritis or interstitial nephritis
• prehospitalization eGFR <30 mL/min/1.73m2.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critical illness with acute kidney injury; See below for detailed inclusion/exclusion criteria	Diagnostic test: Cerebral oxygenation; Cerebral oxygenation will be monitored with the FORESIGHT Elite cerebral oximeter during the first 72h of critical illness, and during subsequent hemodialysis sessions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium Severity	Delirium severity will be calculated from the cumulated Confusion Assessment Method-Intensive Care Unit-7 (CAM-ICU-7) score	Patients will be screened daily in the ICU with the CAM-ICU-7 score up until the date of ICU discharge or day 30 of ICU stay.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Impairment-Kinarm	Patients will undergo a neurocognitive battery with the Kinarm robot and Kinarm standardized tests.	3 months and 12 months
Cognitive Impairment-Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	Patients will undergo assessment with the RBANS administered by a trained researcher.	3 months and 12 months
Medication adherence	Medication adherence will be assessed with the Medication Adherence Rating Scale (MARS)	12 months
Driving safety-1	Driving safety will be assessed by number of motor vehicle accidents.	12 months
Driving safety-2	Driving safety will be assessed by and the Manchester Driver Behavior Questionnaire	12 months
Health care utilization	We will measure emergency department visits and hospital readmissions.	Within 12 months of hospital discharge.
Structural brain imaging	Anonymized and de-identified MRI scans will be processed using MIPAV55 v.7.3.0 and Oxford Centre for Functional MRI of the Brain (FMRIB) Software Library (FSL) v.5.0 medical image processing programs. Scans will be corrected for intensity non-uniformity and transformed into a common image space to adjust for variations in head size and orientation. Skull stripping will be performed. Automated and semi-automated techniques will be used to determine whole-brain volumes from T1-weighted images for analysis of macrostructural brain integrity, as well as FA and MD measures from diffusion-weighted images for analysis of microstructural brain integrity. Brain volumes will be corrected for total intracranial volume to account for head size. Reasons for non-completion of MRI scanning will be recorded. Patients will be used as their own controls over time using a within-subjects design.	3 months and 12 months

Collaborators and Investigators

• Sponsor: Dr. Gordon Boyd

Publications and helpful links

General Publications

• Jawa NA, Holden RM, Silver SA, Scott SH, Day AG, Norman PA, Kwan BYM, Maslove DM, Muscedere J, Boyd JG. Identifying neurocognitive outcomes and cerebral oxygenation in critically ill adults on acute kidney replacement therapy in the intensive care unit: the INCOGNITO-AKI study protocol. BMJ Open. 2021 Aug 17;11(8):e049250. doi: 10.1136/bmjopen-2021-049250.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: DMED-2424-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individualized patient data will be made available upon reasonable request.
• IPD Sharing Time Frame: We are in the final stages of submitting our study protocol for peer review.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• 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