Heart Arrest, Out-Of-HospitalNCT03543371
Neuropsychological Outcome After Cardiac Arrest
An observational study of Heart Arrest, Out-Of-Hospital and Hypoxia-Ischemia, Brain, run by Region Skane at 8 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Arrest, Out-Of-Hospital, Hypoxia-Ischemia, Brain, Cognition Disorders
- What is being tested?
- Neuropsychological assessment
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 13 Jul 2018to 23 May 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Sweden5 sites
Sahlgrenska University Hospital
Gothenburg
Halmstad County Hospital
Halmstad
Helsingborg Hospital
Helsingborg
Skane University Hospital
Lund
Skane University Hospital
Malmö
United Kingdom2 sites
The Essex Cardiothoracic Centre, Basildon and Thurrock University Hospitals NHS Foundation Trust
Basildon, Essex
University Hospital of Wales, Cardiff and Vale University Health Board
Cardiff, Wales
About this study
Official title: 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)
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
- Being tested
- Neuropsychological assessment
- Keywords
- Neuropsychology
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Hypoxia-Ischemia, Brain, Cognition Disorders, Fatigue, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuropsychological assessmentDiagnostic 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).
| Study group | Role | What they receive |
|---|---|---|
| Cardiac Arrest survivors | Cardiac arrest survivors at selected TTM2-sites only. Receives: 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. Receives: Diagnostic Test: Neuropsychological assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive impairment
Cognitive function in OHCA and MI patients, using composite z-scores from the neuropsychological tests grouped by cognitive domain.
Measured: 7 months after the cardiac event
Secondary outcomes (1)
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.
Measured: 7 months post-arrest
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2018
- Study start13 Jul 2018
- Primary completion11 Jan 2021
- Study completion23 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Heart Arrest, Out-Of-HospitalStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University, Halmstad County Hospital, Sahlgrenska University Hospital, Mid and South Essex NHS Foundation Trust, Cardiff and Vale University Health Board, Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Niklas Nielsen, MD, PhD, Study director, Lund UniversityGisela Lilja, PhD, OT, Study director, Lund UniversityTobias Cronberg, MD, PhD, Study director, Lund UniversitySusanna Vestberg, PhD, Lic.Psych., Study director, Lund UniversityErik Blennow Nordström, PhD, Lic.Psych., Principal investigator, Lund University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03543371
- Sponsor's protocol ID
- CardiacArrestLundNeuropsych
- Status last verified
- Sep 2023
- First submitted
- 17 May 2018
- Last updated
- 19 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33028221Blennow 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.
PubMed 39147306Vig 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. 2026 Aug;36(7):1365-1385. doi: 10.1080/09602011.2025.2591784. Epub 2025 Nov 27.
PubMed 41308659Blennow 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.
PubMed 37633944
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03543371
- Acronym / sponsor ID
- CardiacArrestLundNeuropsych
- Conditions
- Heart Arrest, Out-Of-Hospital, Hypoxia-Ischemia, Brain, Cognition Disorders, Psychological Distress, Fatigue, Insomnia
- Keywords
- Neuropsychology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Collaborators
- Lund University, Halmstad County Hospital, Sahlgrenska University Hospital, Mid and South Essex NHS Foundation Trust, Cardiff and Vale University Health Board, Aarhus University Hospital
- Study start
- 13 Jul 2018 (actual)
- Primary completion
- 11 Jan 2021 (actual)
- Study completion
- 23 May 2022 (actual)
- First posted
- 1 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cardiac Arrest survivors | – | Diagnostic Test: Neuropsychological assessmentCardiac arrest survivors at selected TTM2-sites only. |
| Myocardial Infarction patients | – | Diagnostic Test: Neuropsychological assessmentA 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neuropsychological assessmentStandardized 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). | Diagnostic test | Cardiac Arrest survivors, Myocardial Infarction patients |
Primary outcome
Cognitive impairment
Time frame: 7 months after the cardiac event
Cognitive function in OHCA and MI patients, using composite z-scores from the neuropsychological tests grouped by cognitive domain.
1 secondary outcome
Sensitivity and specificity of the neurocognitive screening battery in the main TTM2-trial
Time frame: 7 months post-arrest
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Background: PubMed 33028221Blennow 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.
- Results publication: PubMed 39147306Blennow 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.
- Results publication: PubMed 41308659Vig 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. 2026 Aug;36(7):1365-1385. doi: 10.1080/09602011.2025.2591784. Epub 2025 Nov 27.
- Results publication: PubMed 37633944Blennow 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niklas Nielsen, MD, PhD study director
Lund University
Gisela Lilja, PhD, OT study director
Lund University
Tobias Cronberg, MD, PhD study director
Lund University
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Arrest, Out-Of-Hospital and Hypoxia-Ischemia, Brain, run by Region Skane at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Sweden, United Kingdom, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive impairment (time frame: 7 months after the cardiac event). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03543371, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.