Heart Arrest, Out-Of-HospitalNCT03913065
Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest
An observational study of Heart Arrest, Out-Of-Hospital and Computed Tomography, run by Lund University at 1 site in Sweden.
Trial summary
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) joint guidelines for post-resuscitation care recommend a multimodal approach to prognostication of neurological outcome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Arrest, Out-Of-Hospital, Computed Tomography, Unconsciousness
- What is being tested?
- CT
- How many people
- 400 participants
- Where
- 1 siteSweden
- Study dates
- 18 Nov 2017to 12 Mar 2023
- How long will I take part?
- 6 Months
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with Out-of hospital cardiac arrest included in the TTM-2 trial and randomized to either targeted temperature management at 33°C or early treatment of fever.
Who may be able to join
- Out-of-hospital cardiac arrest
- Presumed cardiac cause of cardiac arrest
- Unconscious with a FOUR-score <M4 (not obeying verbal commands)
- Stable return of spontaneous circulation (20 min)
- Eligible for intensive care treatment without restrictions
- Patient from participating centers, where head CT is routinely performed on all patients still unconscious 48 hours after cardiac arrest
Who cannot join
- Unwitnessed cardiac arrest with an initial rhythm of asystole
- Temperature on admission <30°C.
- Obvious or suspected pregnancy
- Intracranial bleeding
- On ECMO prior to ROSC
- Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy
- Patients from centers not participating in the TTM-2 CT-substudy
- Patients from participating centers not examined with head CT
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest- a TTM-2 Substudy
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) joint guidelines for post-resuscitation care recommend a multimodal approach to prognostication of neurological outcome.
However, head computed tomography (CT) which is commonly used for predicting long-term neurological outcome after cardiac arrest has not yet been examined prospectively in a clinical trial.
The primary purpose of the TTM-2 CT-substudy is to prospectively investigate and compare various methods of diagnosing generalized oedema on CT after cardiac arrest and it´s ability to predict long-term neurological outcome.
Read the detailed description
This study is a sub-study to the international multicenter Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM-2) Trial (ClinicalTrials.gov Identifier: NCT02908308).
All patients from participating centers still unconscious 48 hours after cardiac arrest will be routinely examined with CT. All other inclusion and exclusion criteria as well as treatment, neurological prognostication, withdrawal of life-sustaining therapy or follow-up will be handled according to TTM-2- protocol. Ethical approval for the main trial and this sub-study have been obtained from the Swedish Ethical Review Authority at Lund University (2015/228 and 2017/36). Both a patients´ next of kind or conscious patients have the opportunity to withdraw patients from the trial.
Pseudonymized original CT images will be uploaded to a two-way secured digital platform from Lund University (LUSEC). Two study radiologists blinded from clinical data will perform analyses according to protocol. Various methods of diagnosing generalized oedema will be investigated including eye-balling (oedema "yes"/"no"), as well as manual and automated measurements of the differentiation between the grey and white matter (GWR) by placing circular regions of interest (ROI). Primary outcome is the neurological outcome at 6 months after cardiac arrest using the modified Rankin Scale (mRS).
Secondary outcomes include neurocognitive outcomes such as the Glasgow Outcome Score-Extended version (GOS-E), Symbol-Digit-Modalities-Test (SDMT) and the Montreal Cognitive Assessment Score (MoCA).
The results of the radiological evaluations will also be correlated with other markers of neuronal injury such as biomarkers, clinical neurological information or neurophysiological examinations.
Additional analyses include evaluation of all available CT images of participating patients to investigate if there is any progression or regression of cerebral oedema.
- Being tested
- CT
- Keywords
- Cardiac arrest, Hypothermia, Neurological function, Cardiovascular disease, Cerebral oedema, Cerebral edema, Cerebral ischaemia, Cerebral ischemia, Gray-white-matter differentiation, Grey-white-matter differentiation, ROI, Regions of interest, CT, GWR, Neurological prognostication
- Medical subject headings
- Out-of-Hospital Cardiac Arrest, Unconsciousness, Neurologic Manifestations, Heart Arrest, Hypothermia, Cardiovascular Diseases, Brain Edema, Cerebral Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTDiagnostic test
Head computed tomography on patients still unconscious 48 hours after cardiac arrest.Visual evaluation of generalized oedema ("eye-balling"). Manual and automated measurement of the differentiation of gray and white matter (GWR) using circular regions of interest (ROI).
| Study group | Role | What they receive |
|---|---|---|
| Included patients | Cardiac arrest patients from sites participating in the TTM-2 CT-substudy still unconscious 48 hours after cardiac arrest are routinely examined with head computed tomography as soon as possible after inclusion. Receives: Diagnostic Test: CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Poor functional outcome
Assessed using the modified Rankin Scale (mRS), with a score of 4-6 being a poor outcome.
Measured: 180 days
Secondary outcomes (3)
Exploratory: Neurocognitive outcome
Montreal Cognitive Assessment Scale (MoCA), ranges from 0-30, a score above 26 is considered normal.
Measured: 180 days
Exploratory: Neurocognitive outcome
Symbol Digit Modalities Test (SDMT)
Measured: 180 days
Exploratory: Functional outcome
Glasgow Outcome Scale-Extended version (GOS-E)
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2019
- Study start18 Nov 2017
- Primary completion31 Dec 2022
- Study completion12 Mar 2023
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 Lund UniversityThe 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
- 400 participants (actual)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- Lund University
- Sponsor type
- University, hospital or other
- Collaborators
- Region Skane, Charite University, Berlin, Germany, Halmstad County Hospital, Sahlgrenska University Hospital, Karlstad Central Hospital, Medical University Innsbruck, University Hospital of Wales, Hopital Lariboisière, Nantes University Hospital, University Hospital, Linkoeping
- Responsible party
- Sponsor
- Investigators
- Marion Moseby-Knappe, MD, Principal investigator, Lund University and Skane University Hospitals SwedenTobias Cronberg, MD, PhD, Principal investigator, Lund University and Skane University Hospitals Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03913065
- Sponsor's protocol ID
- TTM-2 CT-substudy
- Status last verified
- Mar 2024
- First submitted
- 5 Apr 2019
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Moseby-Knappe M, Pellis T, Dragancea I, Friberg H, Nielsen N, Horn J, Kuiper M, Roncarati A, Siemund R, Unden J, Cronberg T; TTM-trial investigators. Head computed tomography for prognostication of poor outcome in comatose patients after cardiac arrest and targeted temperature management. Resuscitation. 2017 Oct;119:89-94. doi: 10.1016/j.resuscitation.2017.06.027. Epub 2017 Jul 4.
PubMed 28687281Lang M, Kenda M, Scheel M, Martola J, Wheeler M, Owen S, Johnsson M, Annborn M, Dankiewicz J, Deye N, During J, Halliday T, Jakobsen JC, Lascarrou JB, Levin H, Lilja G, Lybeck A, McGuigan PJ, Rylander C, Sem V, Thomas M, Ullen S, Unden J, Wise MP, Cronberg T, Wasselius J, Nielsen N, Leithner C, Moseby-Knappe M. Radiological signs of hypoxic-ischaemic encephalopathy on head computed tomography for prediction of poor functional outcome after cardiac arrest - a prospective observational cohort study. Resuscitation. 2025 Sep;214:110675. doi: 10.1016/j.resuscitation.2025.110675. Epub 2025 Jun 9.
PubMed 40499676Lang M, Kenda M, Scheel M, Martola J, Wheeler M, Owen S, Johnsson M, Annborn M, Dankiewicz J, Deye N, During J, Friberg H, Halliday T, Jakobsen JC, Lascarrou JB, Levin H, Lilja G, Lybeck A, McGuigan P, Rylander C, Sem V, Thomas M, Ullen S, Unden J, Wise MP, Cronberg T, Wasselius J, Nielsen N, Leithner C, Moseby-Knappe M. Standardised and automated assessment of head computed tomography reliably predicts poor functional outcome after cardiac arrest: a prospective multicentre study. Intensive Care Med. 2024 Jul;50(7):1096-1107. doi: 10.1007/s00134-024-07497-2. Epub 2024 Jun 20.
PubMed 38900283Lang M, Leithner C, Scheel M, Kenda M, Cronberg T, During J, Rylander C, Annborn M, Dankiewicz J, Deye N, Halliday T, Lascarrou JB, Matthew T, McGuigan P, Morgan M, Thomas M, Ullen S, Unden J, Nielsen N, Moseby-Knappe M. Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest: Rationale and design of the prospective TTM2-CT-substudy. Resusc Plus. 2022 Oct 12;12:100316. doi: 10.1016/j.resplu.2022.100316. eCollection 2022 Dec.
PubMed 36267356
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest- a TTM-2 Substudy
- ClinicalTrials.gov ID
- NCT03913065
- Acronym / sponsor ID
- TTM-2 CT-substudy
- Keywords
- Cardiac arrest, Hypothermia, Neurological function, Cardiovascular disease, Cerebral oedema, Cerebral edema, Cerebral ischaemia, Cerebral ischemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- Lund UniversityUniversity, hospital or other
- Collaborators
- Region Skane, Charite University, Berlin, Germany, Halmstad County Hospital, Sahlgrenska University Hospital, Karlstad Central Hospital, Medical University Innsbruck, University Hospital of Wales, Hopital Lariboisière, Nantes University Hospital, University Hospital, Linkoeping
- Study start
- 18 Nov 2017 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 12 Mar 2023 (actual)
- First posted
- 12 Apr 2019 (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.
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) joint guidelines for post-resuscitation care recommend a multimodal approach to prognostication of neurological outcome.
However, head computed tomography (CT) which is commonly used for predicting long-term neurological outcome after cardiac arrest has not yet been examined prospectively in a clinical trial.
The primary purpose of the TTM-2 CT-substudy is to prospectively investigate and compare various methods of diagnosing generalized oedema on CT after cardiac arrest and it´s ability to predict long-term neurological outcome.
Detailed description
This study is a sub-study to the international multicenter Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM-2) Trial (ClinicalTrials.gov Identifier: NCT02908308).
All patients from participating centers still unconscious 48 hours after cardiac arrest will be routinely examined with CT. All other inclusion and exclusion criteria as well as treatment, neurological prognostication, withdrawal of life-sustaining therapy or follow-up will be handled according to TTM-2- protocol. Ethical approval for the main trial and this sub-study have been obtained from the Swedish Ethical Review Authority at Lund University (2015/228 and 2017/36). Both a patients´ next of kind or conscious patients have the opportunity to withdraw patients from the trial.
Pseudonymized original CT images will be uploaded to a two-way secured digital platform from Lund University (LUSEC). Two study radiologists blinded from clinical data will perform analyses according to protocol. Various methods of diagnosing generalized oedema will be investigated including eye-balling (oedema "yes"/"no"), as well as manual and automated measurements of the differentiation between the grey and white matter (GWR) by placing circular regions of interest (ROI). Primary outcome is the neurological outcome at 6 months after cardiac arrest using the modified Rankin Scale (mRS).
Secondary outcomes include neurocognitive outcomes such as the Glasgow Outcome Score-Extended version (GOS-E), Symbol-Digit-Modalities-Test (SDMT) and the Montreal Cognitive Assessment Score (MoCA).
The results of the radiological evaluations will also be correlated with other markers of neuronal injury such as biomarkers, clinical neurological information or neurophysiological examinations.
Additional analyses include evaluation of all available CT images of participating patients to investigate if there is any progression or regression of cerebral oedema.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Included patients | – | Diagnostic Test: CTCardiac arrest patients from sites participating in the TTM-2 CT-substudy still unconscious 48 hours after cardiac arrest are routinely examined with head computed tomography as soon as possible after inclusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with Out-of hospital cardiac arrest included in the TTM-2 trial and randomized to either targeted temperature management at 33°C or early treatment of fever.
Key inclusion criteria (6 listed)
- Out-of-hospital cardiac arrest
- Presumed cardiac cause of cardiac arrest
- Unconscious with a FOUR-score <M4 (not obeying verbal commands)
- Stable return of spontaneous circulation (20 min)
- Eligible for intensive care treatment without restrictions
Key exclusion criteria (8 listed)
- Unwitnessed cardiac arrest with an initial rhythm of asystole
- Temperature on admission <30°C.
- Obvious or suspected pregnancy
- Intracranial bleeding
- On ECMO prior to ROSC
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 |
|---|---|---|
| CTHead computed tomography on patients still unconscious 48 hours after cardiac arrest.Visual evaluation of generalized oedema ("eye-balling"). Manual and automated measurement of the differentiation of gray and white matter (GWR) using circular regions of interest (ROI). | Diagnostic test | Included patients |
Primary outcome
Poor functional outcome
Time frame: 180 days
Assessed using the modified Rankin Scale (mRS), with a score of 4-6 being a poor outcome.
3 secondary outcomes
Exploratory: Neurocognitive outcome
Time frame: 180 days
Exploratory: Neurocognitive outcome
Time frame: 180 days
Exploratory: Functional outcome
Time frame: 180 days
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 22 Mar 2024.
- Results publication: PubMed 28687281Moseby-Knappe M, Pellis T, Dragancea I, Friberg H, Nielsen N, Horn J, Kuiper M, Roncarati A, Siemund R, Unden J, Cronberg T; TTM-trial investigators. Head computed tomography for prognostication of poor outcome in comatose patients after cardiac arrest and targeted temperature management. Resuscitation. 2017 Oct;119:89-94. doi: 10.1016/j.resuscitation.2017.06.027. Epub 2017 Jul 4.
- Derived from this study: PubMed 40499676Lang M, Kenda M, Scheel M, Martola J, Wheeler M, Owen S, Johnsson M, Annborn M, Dankiewicz J, Deye N, During J, Halliday T, Jakobsen JC, Lascarrou JB, Levin H, Lilja G, Lybeck A, McGuigan PJ, Rylander C, Sem V, Thomas M, Ullen S, Unden J, Wise MP, Cronberg T, Wasselius J, Nielsen N, Leithner C, Moseby-Knappe M. Radiological signs of hypoxic-ischaemic encephalopathy on head computed tomography for prediction of poor functional outcome after cardiac arrest - a prospective observational cohort study. Resuscitation. 2025 Sep;214:110675. doi: 10.1016/j.resuscitation.2025.110675. Epub 2025 Jun 9.
- Derived from this study: PubMed 38900283Lang M, Kenda M, Scheel M, Martola J, Wheeler M, Owen S, Johnsson M, Annborn M, Dankiewicz J, Deye N, During J, Friberg H, Halliday T, Jakobsen JC, Lascarrou JB, Levin H, Lilja G, Lybeck A, McGuigan P, Rylander C, Sem V, Thomas M, Ullen S, Unden J, Wise MP, Cronberg T, Wasselius J, Nielsen N, Leithner C, Moseby-Knappe M. Standardised and automated assessment of head computed tomography reliably predicts poor functional outcome after cardiac arrest: a prospective multicentre study. Intensive Care Med. 2024 Jul;50(7):1096-1107. doi: 10.1007/s00134-024-07497-2. Epub 2024 Jun 20.
- Derived from this study: PubMed 36267356Lang M, Leithner C, Scheel M, Kenda M, Cronberg T, During J, Rylander C, Annborn M, Dankiewicz J, Deye N, Halliday T, Lascarrou JB, Matthew T, McGuigan P, Morgan M, Thomas M, Ullen S, Unden J, Nielsen N, Moseby-Knappe M. Prognostic accuracy of head computed tomography for prediction of functional outcome after out-of-hospital cardiac arrest: Rationale and design of the prospective TTM2-CT-substudy. Resusc Plus. 2022 Oct 12;12:100316. doi: 10.1016/j.resplu.2022.100316. eCollection 2022 Dec.
- Website of the TTM2 trialLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Marion Moseby-Knappe, MD principal investigator
Lund University and Skane University Hospitals Sweden
Tobias Cronberg, MD, PhD principal investigator
Lund University and Skane University Hospitals Sweden
1 site in 1 country: 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 Computed Tomography, run by Lund University at 1 site in Sweden.
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 6 inclusion and 8 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 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. 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?
Poor functional outcome (time frame: 180 days). 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 NCT03913065, 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 22 Mar 2024.