Early Neuroprognostication After OHCA

Early Neurological Prognostication of Outcome After Out-of-hospital Cardiac arrest-a STEPCARE Prospective Substudy

This is a prospective observational substudy of the STEPCARE trial ClinicalTrials.gov Identifier: NCT05564754) with the aim to examine whether prognostication of neurological outcome after cardiac arrest can be performed earlier than the 72 h time-point recommended by guidelines today.

Study Overview

• Status: Recruiting
• Conditions: Brain Injuries; Biomarkers; Cardiac Arrest; EEG; CT; Neurological Outcome
• Intervention / Treatment: Diagnostic test: Early neurological prognostication with biomarkers, EEG and CT

Detailed Description

Hypotheses

1. The combination of clinical examination, the brain injury marker neurofilament light (NFL), electroencephalography (EEG), and head computed tomography (CT) predicts poor functional outcome already at 24 h post-arrest without false positive predictions.
2. Any guideline recommended method (EEG/CT/SSEP/clinical examination) fulfilling criteria for a poor outcome will have highly elevated blood levels of NFL, indicating the presence of severe brain injury.
3. Extensive sedation will not affect the prognostic accuracy of our prognostic methods EEG, NFL and CT.

Material and methods

The STEPCARE trial The patient population is adult patients with an out-of-hospital cardiac arrest with a presumed cardiac or unknown cause of arrest randomised in the STEPCARE trial (Sedation, TEmperature and Pressure after out-of-hospital Cardiac Arrest and REsuscitation, ClinicalTrials.gov Identifier: NCT05564754). The STEPCARE trial is an investigator initiated 2x2x2 international multicentre trial which will randomise patients to three intensive care interventions: minimal or higher levels of sedation, fever treatment versus no fever treatment and two different blood pressure targets. The aim of STEPCARE is to examine whether the interventions improves survival or functional outcome after CA. The statistical calculations indicate that 3500 patients are required to obtain sufficient power for our research questions. Patients will be recruited from more than 80 hospitals who have participated in the previous cardiac arrest trials initiated by the Lund University Center for Cardiac Arrest namely the TTM- and TTM2-trials (the to date largest published cardiac arrest trials).

The STEPCARE EARLY-NEURO substudy We will prospectively recruit participating sites who commit to follow the study protocol for participation in the biobank, and routinely examine patients' unconscious at 24 hours with EEG and CT as early as possible after 24 h. Serum and plasma blood samples will be collected prospectively at 12 h, 24 h, 48 h and 72 h post-randomisation, processed on site and transported to the Integrated Biobank in Luxembourg for storage. Biochemical analyses of NFL will be performed in batch after trial completion. The original EEG recordings, SSEP and neuroimaging (CT and MRI) will be collected for central blinded evaluation by study investigators. All patient data will be stored using patients study ID as identification. All patients will be treated according to the STEPCARE trial protocol according to randomisation, treatment, and follow-up. Prediction of neurological outcome performed according to the ERC/ESICM guidelines ≥72 hours post-arrest. Decisions on withdrawal of life-sustaining therapy will not be based on the early examinations alone, but must follow ERC/ESICM recommendations. Functional outcome will be assessed at a face-to-face follow up after six months and classified according to the modified Rankin Scale (mRS). Poor functional outcome will be defined as mRS 4-6 (moderately severe disability, severe disability, or death).

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Marion Moseby-Knappe, MD, PhD; Phone Number: 00464671000; Email: marion.moseby_knappe@med.lu.se

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki Hospital
    • Contact: Markus Skrifvars, Prof
    • Sub-Investigator: Marjaana Tiainen, MD, PhD
• Germany
  • Berlin, Germany
    • Recruiting
    • Charite University Hospital
    • Contact: Christoph Leithner, MD
• Sweden
  • Helsingborg, Sweden
    • Recruiting
    • Helsingborgs Hospital
    • Contact: Niklas Nielsen, Prof
  • Lund, Sweden
    • Recruiting
    • Skane University Hospital
    • Contact: Josef Dankiewicz, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult cardiac arrest patients with an out-of-hospital cardiac arrest of any non-traumatic cause treated at hospitals recruiting patients to the STEPCARE neuroprognostication substudy

Description

Inclusion Criteria:

Adult cardiac arrest patients with an out-of-hospital cardiac arrest of non-traumatic cause treated at hospitals recruiting patients to the STEPCARE neuroprognostication substudy. Other inclusion criteria include:

• a minimum of 20 minutes without chest compressions
• Unconsciousness defined as not being able to obey verbal commands (FOUR-score motor response of <4) or being intubated and sedated because of agitation after sustained ROSC
• Eligible for intensive care without restrictions or limitations
• Inclusion within 4 hours of ROSC

Exclusion Criteria:

• On ECMO prior to randomisation
• Pregnancy
• Suspected or confirmed intracranial hemorrhage
• Previously randomised in the STEPCARE trial
• Patients with limitations in level-of-care due to for example generalized malignancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome	Poor outcome defined as modified Rankin Scale 4-6	Six months post-randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood levels of brain injury markers	Neurofilament light	Samples collected at 12-72 hours post-randomisation

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Charite University, Berlin, Germany; University of Helsinki; Skane University Hospital; Helsingborgs Hospital
• Investigators: Study Chair: Niklas Nielsen, MD, PhD, Lund University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Heart Arrest
• Other Study ID Numbers: STEPCARE EARLY-NEURO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon reasonable request following publication

Drug and device information, study documents

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