Head Computed Tomography for Predicting Neurological Outcome After Cardiac Arrest

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.

Study Overview

• Status: Completed
• Conditions: Unconsciousness; Heart Arrest, Out-Of-Hospital; Computed Tomography; Neurologic Deficits
• Intervention / Treatment: Diagnostic test: CT

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 Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Sweden
  • Skania
    • Lund, Skania, Sweden, 22185
      • Marion Moseby-Knappe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Diagnostic test: CT; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Poor functional outcome	Assessed using the modified Rankin Scale (mRS), with a score of 4-6 being a poor outcome.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Neurocognitive outcome	Montreal Cognitive Assessment Scale (MoCA), ranges from 0-30, a score above 26 is considered normal.	180 days
Exploratory: Neurocognitive outcome	Symbol Digit Modalities Test (SDMT)	180 days
Exploratory: Functional outcome	Glasgow Outcome Scale-Extended version (GOS-E)	180 days

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Charite University, Berlin, Germany; Sahlgrenska University Hospital, Sweden; Nantes University Hospital; Medical University Innsbruck; Region Skane; Halmstad County Hospital; University Hospital, Linkoeping; Karlstad Central Hospital; Hopital Lariboisière; University Hospital of Wales
• Investigators: Principal Investigator: Marion Moseby-Knappe, MD, Lund University and Skane University Hospitals Sweden; Principal Investigator: Tobias Cronberg, MD, PhD, Lund University and Skane University Hospitals Sweden

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Website of the TTM2 trial

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2017
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): March 12, 2023

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Cardiac arrest; CT; Hypothermia; Neurological function; Cerebral edema; Cerebral ischemia; Cerebral oedema; Cerebral ischaemia; Gray-white-matter differentiation; Grey-white-matter differentiation; ROI; Regions of interest; GWR; Neurological prognostication
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Consciousness Disorders; Heart Arrest; Unconsciousness; Out-of-Hospital Cardiac Arrest; Neurologic Manifestations
• Other Study ID Numbers: TTM-2 CT-substudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No