Clinical trial NCT01946932: Cognitive Impairment Following Cardiac Arrest and Target Temperature Management
Official title: Cognitive Impairment Following Cardiac Arrest and Target Temperature Management
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Arrest
Out-of-hospital Cardiac Arrest
Cognition Disorders
Brain Injury
Keywords: Induced hypothermia
Mild induced hypothermia
Resuscitation
Therapeutic hypothermia
Neurological function
Cardiovascular diseases
Rehabilitation
Quality of life
Cognition
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Copenhagen University Hospital, Denmark
name: Azienda Ospedaliera Santa Maria Degli Angeli
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: University Hospital of Wales
First posted: 2013-09-20
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Rivermead Behavioural Memory Test (RBMT)
timeFrame: 180 days after Cardiac Arrest (CA) or Myocardial Infarction (MI)
measure: Frontal Assessment Battery (FAB)
timeFrame: 180 days after CA or MI
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: 180 days after CA or MI
Secondary outcomes:
measure: Mayo-Portland Adaptability Inventory-4 (MPAI-4)
timeFrame: 180 days after CA or MI
measure: Short-Form Questionnaire 36 version 2 (SF-36v2)
timeFrame: 180 days after CA or MI
measure: Zarit Burden Interview
timeFrame: 180 days after CA or MI
measure: Hospital Anxiety and Depression rating Scale (HADS)
timeFrame: 180 days after CA or MI
measure: Two Simple Questions (TSQ)
timeFrame: 180 days after CA or MI
measure: Informant Questionnaire on Cognitive Decline (IQCODE)
timeFrame: 180 days after CA or MI
measure: MiniMental Status Examination (MMSE)
timeFrame: 180 days after CA or MI
measure: Cerebral Performance Category (CPC)
timeFrame: 180 days after CA or MI
measure: modified Rankin Scale
timeFrame: 180 days after CA or MI
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Genova
country: Italy
facility: San Martino Hospital
city: Pordenone
country: Italy
facility: Santa Maria degli Angeli Hospital
city: Trieste
country: Italy
facility: Ospedale Universitario di Cattinaria
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Leeuwarden
country: Netherlands
facility: Leeuwarden Hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital, Thorax
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital, Östra
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Karlstad
country: Sweden
facility: Karlstad Central Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital, Lund
city: Malmoe
country: Sweden
facility: Skåne University Hospital, Malmö
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: St Georges' Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
Study officials:
affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden and Department of Neurology, Skåne University Hospital, Lund, Sweden
name: Tobias Cronberg, MD, PhD
role: STUDY_CHAIR
affiliation: Department of Clinical Sciences, Lund University, Lund Sweden and Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden
name: Niklas Nielsen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Heart Centrem Copenhagen University, Copenhagen, Denmark
name: Jesper Kjaergaard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Intensive Care, Academic Medical Centrum, Amsterdam, Netherlands
name: Janneke Horn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Intensive Care Unit Santa Maria Degli Angeli, Pordenonde, Italy
name: Tommaso Pellis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Adult Critical Care, University Hospital of Wales, Cardiff, Untied Kingdom
name: Matthew P Wise, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lund University Hospital, Lund, Sweden
name: Gisela Lilja, OT
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.