Clinical trial NCT03913065: Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest
Official title: Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest- a TTM-2 Substudy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Arrest, Out-Of-Hospital
Computed Tomography
Unconsciousness
Neurologic Deficits
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
Lead sponsor: Lund University
Sponsor class: OTHER
Collaborators: name: Region Skane
name: Charite University, Berlin, Germany
name: Halmstad County Hospital
name: Sahlgrenska University Hospital
name: Karlstad Central Hospital
name: Medical University Innsbruck
name: University Hospital of Wales
name: Hopital Lariboisière
name: Nantes University Hospital
name: University Hospital, Linkoeping
First posted: 2019-04-12
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
* Inclusion within 180 minutes of ROSC
* Patient from participating centers, where head CT is routinely performed on all patients still unconscious 48 hours after cardiac arrest

Exclusion Criteria:

* 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

Primary outcomes:
measure: Poor functional outcome
timeFrame: 180 days
Secondary outcomes:
measure: Exploratory: Neurocognitive outcome
timeFrame: 180 days
measure: Exploratory: Neurocognitive outcome
timeFrame: 180 days
measure: Exploratory: Functional outcome
timeFrame: 180 days
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Marion Moseby-Knappe
state: Skania
Study officials:
affiliation: Lund University and Skane University Hospitals Sweden
name: Marion Moseby-Knappe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lund University and Skane University Hospitals Sweden
name: Tobias Cronberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Lang 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.