Cognitive Impairment Following Cardiac Arrest and Target Temperature Management

This is a steering group approved substudy to the Target Temperature Management trial (TTM, ClinicalTrials.gov Identifier: NCT01020916). TTM compares the effect of two strictly controlled temperature regimes for survivors of out-of-hospital cardiac arrest.

The primary aim of this sub-study is to compare the amount of cognitive impairment in cardiac arrest survivors treated with 33 degrees and 36 degrees and with a matched group of control patients with myocardial infarction.

Our secondary aims are:

• To investigate the impact of cognitive impairment on our patients' ability to participate in society and their health related quality of life.
• To investigate the relationship between our patients cognitive impairments and their relatives/informants health related quality of life and feelings of burden.
• To test the hypothesis that the simple cognitive screening battery used in the TTM main trial is sensitive enough to detect all patients with significant cognitive disability.

Study Overview

• Status: Completed
• Conditions: Brain Injury; Cognition Disorders; Heart Arrest; Out-of-hospital Cardiac Arrest
• Intervention / Treatment: Other: Temperature treatment

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Italy
  • Genova, Italy
    • San Martino Hospital
  • Pordenone, Italy
    • Santa Maria degli Angeli Hospital
  • Trieste, Italy
    • Ospedale Universitario di Cattinaria
• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum (AMC)
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Leeuwarden, Netherlands
    • Leeuwarden Hospital
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital, Thorax
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital, Östra
  • Helsingborg, Sweden
    • Helsingborg Hospital
  • Karlstad, Sweden
    • Karlstad Central Hospital
  • Lund, Sweden
    • Skåne University Hospital, Lund
  • Malmoe, Sweden
    • Skåne University Hospital, Malmö
  • Örebro, Sweden
    • Orebro University Hospital
• United Kingdom
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Cardiff, United Kingdom
    • University Hospital of Wales
  • London, United Kingdom
    • St Georges' Hospital
  • Reading, United Kingdom
    • Royal Berkshire NHS foundation trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• Out-of-Hospital Cardiac Arrest (OHCA)of presumed cardiac cause
• Unconsciousness after sustained return of spontaneous circulation (ROSC)

Exclusion Criteria at time for inclusion in the TTM study:

• Known bleeding diathesis
• Suspected or confirmed acute intracranial bleeding
• Suspected or confirmed stroke
• Unwitnessed asystole
• Known limitations in therapy and Do Not Resuscitate-order
• Known disease making 180 days survival unlikely
• Known prearrest status Cerebral Performance Category (CPC)3 or 4

• Temperature <30°on admission

  • 4 hours (240 minutes) from ROSC to screening
• Systolic blood pressure <80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump
• In-hospital cardiac arrest
• OHCA of presumed non-cardiac arrest cause

Additional Exclusion criteria for the sub-study:

• Disability to speak the site language well enough to complete tests without interpreter
• Controls should never have suffered a cardiac arrest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Cardiac Arrest 33°; survivors with temperature treatment 33°	Other: Temperature treatment
ACTIVE_COMPARATOR: Cardiac Arrest survivors 36°; survivors with temperature treatment 36°	Other: Temperature treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rivermead Behavioural Memory Test (RBMT)	Memory test	180 days after Cardiac Arrest (CA) or Myocardial Infarction (MI)
Frontal Assessment Battery (FAB)	Screening of Executive functions	180 days after CA or MI
Symbol Digit Modalities Test (SDMT)	Assess attention, mental speed and concentration	180 days after CA or MI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mayo-Portland Adaptability Inventory-4 (MPAI-4)	Self rating of impairments, adjustment, and participation (in the society)	180 days after CA or MI
Short-Form Questionnaire 36 version 2 (SF-36v2)	Questionnaire of health-related quality of life, both for patient and informant/relative/caregiver	180 days after CA or MI
Zarit Burden Interview	Questionnaire for caregiver/informant/relative's perception of burden	180 days after CA or MI
Hospital Anxiety and Depression rating Scale (HADS)	Anxiety and Depression questionnaire	180 days after CA or MI
Two Simple Questions (TSQ)	Self rating of everyday activities and cognition	180 days after CA or MI
Informant Questionnaire on Cognitive Decline (IQCODE)	Patients cognitive functioning in everyday life, questionnaire completed by informant/relative/caregiver	180 days after CA or MI
MiniMental Status Examination (MMSE)	General cognitive screening	180 days after CA or MI
Cerebral Performance Category (CPC)	Scale for general neurological outcome	180 days after CA or MI
modified Rankin Scale	Scale for general outcome	180 days after CA or MI

Collaborators and Investigators

• Sponsor: Region Skane
• Collaborators: Lund University; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Copenhagen University Hospital, Denmark; Copenhagen Trial Unit, Center for Clinical Intervention Research; University Hospital of Wales; Azienda Ospedaliera Santa Maria Degli Angeli
• Investigators: Study Chair: Tobias Cronberg, MD, PhD, Department of Clinical Sciences, Lund University, Lund, Sweden and Department of Neurology, Skåne University Hospital, Lund, Sweden; Principal Investigator: Niklas Nielsen, MD,PhD, Department of Clinical Sciences, Lund University, Lund Sweden and Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden; Principal Investigator: Jesper Kjaergaard, MD, PhD, The Heart Centrem Copenhagen University, Copenhagen, Denmark; Principal Investigator: Janneke Horn, MD, PhD, Department of Intensive Care, Academic Medical Centrum, Amsterdam, Netherlands; Principal Investigator: Tommaso Pellis, MD, PhD, Intensive Care Unit Santa Maria Degli Angeli, Pordenonde, Italy; Principal Investigator: Matthew P Wise, MD, PhD, Adult Critical Care, University Hospital of Wales, Cardiff, Untied Kingdom; Study Director: Gisela Lilja, OT, Lund University Hospital, Lund, Sweden

Publications and helpful links

General Publications

• Cronberg T, Lilja G, Rundgren M, Friberg H, Widner H. Long-term neurological outcome after cardiac arrest and therapeutic hypothermia. Resuscitation. 2009 Oct;80(10):1119-23. doi: 10.1016/j.resuscitation.2009.06.021. Epub 2009 Jul 23.
• Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, Brunetti I, Cranshaw J, Cronberg T, Edqvist K, Erlinge D, Gasche Y, Glover G, Hassager C, Horn J, Hovdenes J, Johnsson J, Kjaergaard J, Kuiper M, Langorgen J, Macken L, Martinell L, Martner P, Pellis T, Pelosi P, Petersen P, Persson S, Rundgren M, Saxena M, Svensson R, Stammet P, Thoren A, Unden J, Walden A, Wallskog J, Wanscher M, Wise MP, Wyon N, Aneman A, Friberg H. Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design. Am Heart J. 2012 Apr;163(4):541-8. doi: 10.1016/j.ahj.2012.01.013.
• Heimburg K, Cronberg T, Tornberg AB, Ullen S, Friberg H, Nielsen N, Hassager C, Horn J, Kjaergaard J, Kuiper M, Rylander C, Wise MP, Lilja G. Self-reported limitations in physical function are common 6 months after out-of-hospital cardiac arrest. Resusc Plus. 2022 Jul 19;11:100275. doi: 10.1016/j.resplu.2022.100275. eCollection 2022 Sep.
• Lilja G, Nielsen N, Bro-Jeppesen J, Dunford H, Friberg H, Hofgren C, Horn J, Insorsi A, Kjaergaard J, Nilsson F, Pelosi P, Winters T, Wise MP, Cronberg T. Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest. Circ Cardiovasc Qual Outcomes. 2018 Jan;11(1):e003566. doi: 10.1161/CIRCOUTCOMES.117.003566.
• Lilja G, Nilsson G, Nielsen N, Friberg H, Hassager C, Koopmans M, Kuiper M, Martini A, Mellinghoff J, Pelosi P, Wanscher M, Wise MP, Ostman I, Cronberg T. Anxiety and depression among out-of-hospital cardiac arrest survivors. Resuscitation. 2015 Dec;97:68-75. doi: 10.1016/j.resuscitation.2015.09.389. Epub 2015 Oct 9.
• Lilja G, Nielsen N, Friberg H, Horn J, Kjaergaard J, Nilsson F, Pellis T, Wetterslev J, Wise MP, Bosch F, Bro-Jeppesen J, Brunetti I, Buratti AF, Hassager C, Hofgren C, Insorsi A, Kuiper M, Martini A, Palmer N, Rundgren M, Rylander C, van der Veen A, Wanscher M, Watkins H, Cronberg T. Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33 degrees C versus 36 degrees C. Circulation. 2015 Apr 14;131(15):1340-9. doi: 10.1161/CIRCULATIONAHA.114.014414. Epub 2015 Feb 13.
• Lilja G, Nielsen N, Friberg H, Horn J, Kjaergaard J, Pellis T, Rundgren M, Wetterslev J, Wise MP, Nilsson F, Cronberg T. Cognitive function after cardiac arrest and temperature management; rationale and description of a sub-study in the Target Temperature Management trial. BMC Cardiovasc Disord. 2013 Oct 12;13:85. doi: 10.1186/1471-2261-13-85.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: September 12, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (ESTIMATE): September 20, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 5, 2013
• Last Update Submitted That Met QC Criteria: December 4, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Rehabilitation; Quality of life; Therapeutic hypothermia; Cognition; Cardiovascular diseases; Resuscitation; Induced hypothermia; Mild induced hypothermia; Neurological function
• Additional Relevant MeSH Terms: Mental Disorders; Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Cognitive Dysfunction; Heart Arrest; Cognition Disorders; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: TTMcogsub