Neuropsychological Outcome After Cardiac Arrest

Study Overview
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Brief Summary
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This study is a sub-study to the large pragmatic Target Temperature Management 2 Trial (TTM2-trial, ClinicalTrials.gov Identifier: NCT02908308), assessing effectiveness of controlled hypothermia after out-of-hospital cardiac arrest (OHCA). This study is designed to provide detailed information on cognition after OHCA and its relationship to associated factors as emotional function, fatigue, and sleep. A secondary aim is to utilize this information to validate a neurocognitive screening battery used 6 months after OHCA in the TTM2-trial. Approximately 7 and 24 months after OHCA, survivors at selected TTM2 study sites will perform a standardized neuropsychological assessment including performance-based tests of cognition and questionnaires of behavioral and emotional function, fatigue, and insomnia. At 1:1 ratio, a control group of myocardial infarction (MI) patients but no occurrence of cardiac arrest will be recruited and perform the same test battery. Group differences at 7 and 24 months will be analyzed per cognitive domain (verbal, visual/constructive, short-term working memory, episodic memory, processing speed, executive functions). Results of the OHCA survivors on the TTM2 neurocognitive screening battery will be compared with neuropsychological test results at 7 months time.

Official Title
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Neuropsychological Outcome After Cardiac Arrest: A Prospective Case Control Sub-study of the Targeted Hypothermia Versus Targeted Normothermia After out-of Hospital Cardiac Arrest Trial (TTM2)

Conditions
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Heart Arrest, Out-Of-Hospital, Hypoxia-Ischemia, Brain, Cognition Disorders, Psychological Distress, Fatigue, Insomnia

Intervention / Treatment
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* Diagnostic Test: Neuropsychological assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OHCA of a presumed cardiac or unknown cause (OHCA cohort only) Sustained return of spontaneous circulation (ROSC) during intensive care - defined as 20 minutes with signs of circulation without the need for chest compressions (OHCA cohort only) Unconsciousness - defined as not being able to obey verbal commands (FOUR-score motor response of <4) and no verbal response to pain after sustained ROSC (OHCA cohort only) Inclusion within 180 minutes of ROSC (OHCA cohort only) During intensive care - eligible for intensive care without restrictions or limitations (OHCA cohort only) MI with performed coronary angiography (MI cohort only) Exclusion Criteria: Temperature on admission <30°C (OHCA cohort only) On extracorporeal membrane oxygenation (ECMO) prior to return of spontaneous circulation (OHCA cohort only) Obvious or suspected pregnancy Intracranial bleeding (OHCA cohort only) Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy Clinical dementia diagnosis before the event Inability to speak the local language well enough to complete the assessment without assistance from an interpreter Inability to meet for a face-to-face examination Clinical Frailty Scale Index ≥8, indicating very severe frailty Cardiac arrest before or in connection with MI (MI cohort only) Active substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiac Arrest survivors<br>Cardiac arrest survivors at selected TTM2-sites only. | Diagnostic Test: Neuropsychological assessment<br>* Standardized neuropsychological battery consisting of the following tests and questionnaires: Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Vocabulary, Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency, WAIS-IV Block Design, WAIS-IV Matrix Reasoning, WAIS-IV Digit Span, Wechsler Memory Scale - Third Edition (WMS-III) Spatial Span, Rey Auditory Verbal Learning Test (RAVLT), WMS-III Logical Memory, Brief Visuospatial Memory Test-Revised (BVMT-R), Trail Making Test (TMT) A & B, D-KEFS Color Word Interference Test, Behavioral Assessment of the Dysexecutive Syndrome Dysexecutive Questionnaire (BADS DEX), Multidimensional Fatigue Inventory (MFI-20), Minimal Insomnia Symptom Scale (MISS), Hospital Anxiety and Depression Scale (HADS).<br>|
| Myocardial Infarction patients<br>A control group from a cohort of patients with myocardial infarction with performed coronary angiography but no occurrence of cardiac arrest will be recruited at 1:1 ratio. | Diagnostic Test: Neuropsychological assessment<br>* Standardized neuropsychological battery consisting of the following tests and questionnaires: Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Vocabulary, Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency, WAIS-IV Block Design, WAIS-IV Matrix Reasoning, WAIS-IV Digit Span, Wechsler Memory Scale - Third Edition (WMS-III) Spatial Span, Rey Auditory Verbal Learning Test (RAVLT), WMS-III Logical Memory, Brief Visuospatial Memory Test-Revised (BVMT-R), Trail Making Test (TMT) A & B, D-KEFS Color Word Interference Test, Behavioral Assessment of the Dysexecutive Syndrome Dysexecutive Questionnaire (BADS DEX), Multidimensional Fatigue Inventory (MFI-20), Minimal Insomnia Symptom Scale (MISS), Hospital Anxiety and Depression Scale (HADS).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive impairment | Cognitive function in OHCA and MI patients, using composite z-scores from the neuropsychological tests grouped by cognitive domain. | 7 months after the cardiac event | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of the neurocognitive screening battery in the main TTM2-trial | Validation of the neurocognitive screening battery in OHCA patients, using the detailed neuropsychological test battery as a gold standard with sensitivity and specificity analyses. Here, patients will be considered to have a cognitive impairment if they meet any of the following criteria on the neuropsychological tests: 1) an impaired composite z-score defined as z ≤ - 1.65 in at least one cognitive domain; 2) z ≤ - 1.65 in at least two scores used for cognitive domain calculation. Cut-scores for indicated impairment on the neurocognitive screening battery will be < 26 on the MoCA, z≤-1 on the SDMT, ≥3.08 on the IQCODE-CA and the answer no to question 2 at the TSQ. | 7 months post-arrest | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropsychology