Neuropsychological Outcome After Cardiac Arrest

NCT03543371 | Completed

• 1 other identifier: CardiacArrestLundNeuropsych
• Study Type: observational
• Target: 200
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

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

Keywords

Neuropsychology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Sensitivity and specificity of the neurocognitive screening battery in the main TTM2-trial

  7 months post-arrest

Other Outcomes (1)

• Change in cognitive function

  7 months, 24 months after the cardiac event

Study Arms (2)

Cardiac Arrest survivors

Cardiac arrest survivors at selected TTM2-sites only.

Diagnostic Test: Neuropsychological assessment

Myocardial Infarction patients

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

Interventions

Neuropsychological assessment DIAGNOSTIC_TEST

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).

Cardiac Arrest survivors; Myocardial Infarction patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

OHCA survivors at TTM2-sites participating in this study. Survivors are invited to partake in this study at the regular six-month follow-up of the TTM2-trial. The cohort of MI patients acting as controls are recruited and assessed at one participating site per country through quality registers.

You may qualify if:

• 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)
• During intensive care - eligible for intensive care without restrictions or limitations (OHCA cohort only)
• MI with performed coronary angiography (MI cohort only)

You may not qualify if:

• 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

Sponsors & Collaborators

• Region Skane: lead
• Lund University: collaborator
• Halmstad County Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• Mid and South Essex NHS Foundation Trust: collaborator
• Cardiff and Vale University Health Board: collaborator
• Aarhus University Hospital: collaborator

Study Sites (8)

Aarhus University Hospital

Aarhus, Denmark

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Halmstad County Hospital

Halmstad, Sweden

Location

Helsingborg Hospital

Helsingborg, Sweden

Location

Skane University Hospital

Lund, Sweden

Location

Skane University Hospital

Malmo, Sweden

Location

The Essex Cardiothoracic Centre, Basildon and Thurrock University Hospitals NHS Foundation Trust

Basildon, Essex, United Kingdom

Location

University Hospital of Wales, Cardiff and Vale University Health Board

Cardiff, Wales, United Kingdom

Location

Related Publications (4)

• Blennow Nordstrom E, Lilja G, Vestberg S, Ullen S, Friberg H, Nielsen N, Heimburg K, Evald L, Mion M, Segerstrom M, Grejs AM, Keeble T, Kirkegaard H, Ljung H, Rose S, Wise MP, Rylander C, Unden J, Cronberg T. 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). BMC Cardiovasc Disord. 2020 Oct 7;20(1):439. doi: 10.1186/s12872-020-01721-9.

  PMID: 33028221 BACKGROUND

• Blennow Nordstrom E, Evald L, Mion M, Segerstrom M, Vestberg S, Ullen S, Heimburg K, Gregersen Oestergaard L, Grejs AM, Keeble TR, Kirkegaard H, Rylander C, Wise MP, Lilja G. Combined use of the Montreal Cognitive Assessment and Symbol Digit Modalities Test improves neurocognitive screening accuracy after cardiac arrest: A validation sub-study of the TTM2 trial. Resuscitation. 2024 Sep;202:110361. doi: 10.1016/j.resuscitation.2024.110361. Epub 2024 Aug 13.

  PMID: 39147306 RESULT

• Vig A, Vestberg S, Evald L, Mion M, Segerstrom M, Ullen S, Arestedt K, Nielsen N, Cronberg T, Lilja G, Blennow Nordstrom E. Psychometric properties of the Dysexecutive Questionnaire (DEX) in individuals with a previous cardiac event. Neuropsychol Rehabil. 2025 Nov 27:1-21. doi: 10.1080/09602011.2025.2591784. Online ahead of print.

  PMID: 41308659 RESULT

• Blennow Nordstrom E, Vestberg S, Evald L, Mion M, Segerstrom M, Ullen S, Bro-Jeppesen J, Friberg H, Heimburg K, Grejs AM, Keeble TR, Kirkegaard H, Ljung H, Rose S, Wise MP, Rylander C, Unden J, Nielsen N, Cronberg T, Lilja G. Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial. Crit Care. 2023 Aug 26;27(1):328. doi: 10.1186/s13054-023-04617-0.

  PMID: 37633944 RESULT

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Hypoxia-Ischemia, Brain; Cognition Disorders; Fatigue; Sleep Initiation and Maintenance Disorders

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders

Study Officials

• Niklas Nielsen, MD, PhD

  Lund University

  STUDY DIRECTOR

• Gisela Lilja, PhD, OT

  Lund University

  STUDY DIRECTOR

• Tobias Cronberg, MD, PhD

  Lund University

  STUDY DIRECTOR

• Susanna Vestberg, PhD, Lic.Psych.

  Lund University

  STUDY DIRECTOR

• Erik Blennow Nordström, PhD, Lic.Psych.

  Lund University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 1, 2018
• Study Start: July 13, 2018
• Primary Completion: January 11, 2021
• Study Completion: May 23, 2022
• Last Updated: December 19, 2025

Record last verified: 2023-09

Locations

GB (2); SE (5); DK (1)