Early WAKE-up Predictors After Out-of-Hospital Cardiac Arrest (WAKE-OHCA)

Early Wake-up Predictors After Out-of-hospital Cardiac Arrest - an Observational, Multicenter Substudy of the DANOHCA Trial

WAKE-OHCA is a prospective observational substudy of the Danish Out-of-Hospital Cardiac Arrest (DANOHCA) trial, identifier NCT05895838. The aim is to collect early neuromonitoring data to identify key predictors of successful wake-up.

Study Overview

• Status: Recruiting
• Conditions: Anoxic Brain Injury; Optic Nerve Sheath Diameter; Cardiac Arrest (CA); EEG; Neurological Outcome; Comatose Survivors of Cardiac Arrest; Transcranial Doppler Ultrasound; Pupillometry
• Intervention / Treatment: Diagnostic test: Automated Pupillometry; Diagnostic test: Transcranial Doppler Ultrasound; Diagnostic test: Optic Nerve Sheath Diameter; Diagnostic test: Continuous EEG and EEG Reactivity

Detailed Description

Background:

Post-resuscitation care following out-of-hospital cardiac arrest remains a critical area of research to optimize neurological recovery and cardiovascular outcomes. Recent findings from the Targeted Temperature Management (TTM) trials have led to the discontinuation of therapeutic hypothermia in Denmark, eliminating the need for deep sedation. The optimal sedation strategy in post-resuscitation care remains unknown, with sedation hypothesized to be neuroprotective controlling intracranial pressure but also known to be harmful and associated with adverse outcomes such as delirium, ventilator associated pneumonia, venous thromboembolism, prolonged intensive care unit (ICU) stay, delayed mobilization and patient prognostication.

Though there is emerging interest in early weaning from sedation within post-resuscitation care, limited data exist on its feasibility, prognostic implications and cost-effectiveness. Certain neuromonitoring modalities including automated pupillometry, transcranial doppler and electroencephalography (EEG) have shown promising prognostic properties, also in predicting favorable outcomes. However, sparse literature exists on early (<6 hours) prognostication related to length of sedation, and further knowledge in this area is needed to support clinical decision making.

The Danish Out-of-Hospital Cardiac Arrest (DANOHCA) study (NCT05895838) is an on-going multicenter randomized trial enrolling 1,000 participants to early wake-up (<6 hours) or standard (28-36 hours) length of sedation. This provides an opportunity to further understand neuroprognostication related to length of sedation in post-resuscitation care.

Aim and hypothesis:

This present study is designed within the context of the DANOHCA trial with the aim of identifying patient and neuromonitoring predictors of successful early and late wake-up.

The hypothesis is: Specific patient variables and neuromonitoring parameters are associated with successful wake-up.

Materials and Methods:

WAKE-OHCA will be conducted as a two-part analysis with 1) entire DANOHCA cohort (n=1,000 participants) with ICU admission data and 2) neuromonitoring data collected within the ICU on the patient cohorts at two Danish university hospital sites (Aarhus University Hospital and Rigshospitalet) during the study inclusion period (anticipated n=250 participants, with the exception of n=100 participants for EEG measurements, as these will only be performed at Aarhus University Hospital site).

DANOHCA inclusion criteria are: Out-of-hospital cardiac arrest of a presumed cardiac cause, age > 18 years, sustained return of spontaneous circulation for more than 20 minutes, unconscious upon admission.

The first part will include baseline characteristics, cardiac arrest data, and initial biochemistry. Data is collected from Danish prehospital patient journal (PPJ), electronic patient journals (EPJ, Sundhedsplatformen), Danish cardiac arrest registry and DANOHCA patient database.

The second part will include the following non-invasive neuromonitoring data collected prospectively at 0-6 hours, 20-28 hours, 44-52 hours and 66-72 hours after enrolment:

• Bilateral automated pupillometry
• Transcranial doppler evaluating both middle cerebral arteries.
• Bilateral Optic Nerve Sheath Diameter measured by ultrasound.
• Continuous 4-channel EEG background activity and EEG reactivity tests.

These will provide insight on early neurological status and recovery patterns, cerebral hemodynamics and intracranial pressure. Neuromonitoring data will only be collected on participants that are still comatose. Clinicians will be blinded from collected data, and it will have no impact on participants' treatment.

Automated pupillometry will be done with a NeurOptics NPi-200 pupillometer (NeurOptics, Irvine, California, USA). Transcranial doppler and ONSD measurements will be conducted with a Vivid S70N (GE Healthcare, Chicago, IL, USA) and analysed using Echopac (GE Healthcare, Chicago, IL, USA). EEG measurements will be done with Mindray BeneVision N-series with an aEEG module (Shenzhen Mindray Bio-Medical Electronics Co., Nanshan, Shenzhen, China).

Logistic regression analysis will be conducted to explore the association between participant and neuromonitoring variables and successful wake-up with unsuccessful wake-up as reference group. Secondary analyses will investigate how neuromonitoring variables perform in predicting patient outcomes (mortality, neurological outcome) in the early and late wake-up groups as well as how serial neuromonitoring variables are associated with successful wake-up at later stages.

Significance:

By identifying key predictors of early wake-up success, this project may refine patient selection, optimize individualized treatment, and enhance prognostication. Insights into neuromonitoring could improve clinical decision-making and reduce unnecessary sedation, minimizing associated complications.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Christopher Torp Lohse, MD; Phone Number: +4526745886; Email: chtorp@rm.dk
• Study Contact Backup: Name: Anders Grejs, MD, PhD; Phone Number: +4551948171; Email: andgre@rm.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, DK-8200
    • Recruiting
    • Department of Intensive Care Medicine
    • Contact: Christopher Torp Lohse, MD; Phone Number: +4526745886; Email: chtorp@rm.dk
    • Contact: Anders Grejs, MD, PhD; Phone Number: +4551948171; Email: andgre@rm.dk
    • Principal Investigator: Christopher Torp Lohse, MD
  • Copenhagen, Denmark, DK-2100
    • Recruiting
    • Department of Cardiology, The Heart Centre, Rigshospitalet
    • Contact: Simon Schneekloth, MD; Phone Number: +4553586606; Email: simon.schneekloth.02@regionh.dk
    • Principal Investigator: Simon Schneekloth, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients enrolled in the DANOHCA trial at Aarhus University Hospital and Rigshospitalet.

Description

Inclusion Criteria:

• Age ≥18 years
• OHCA of presumed cardiac cause
• Sustained ROSC, defined as persistent signs of circulation and no need for chest compressions or mechanical circulatory support for 20 minutes
• Unconsciousness (GCS <9) (patients not able to obey verbal commands) after sustained ROSC at the time of randomization

Exclusion Criteria:

• Females of childbearing potential if pregnancy is suspected (unless a negative HCG test can rule out pregnancy within the inclusion window)
• Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient)
• Suspected or confirmed acute intracranial bleeding
• Suspected or confirmed acute stroke
• Unwitnessed asystole
• Known limitations in therapy and Do Not Resuscitate-order
• Known disease making 180 days survival unlikely
• Known pre-arrest CPC 3 or 4 functional status
• >3 hours (180 minutes) from ROSC to screening
• Systolic blood pressure <80 mm Hg despite fluid loading/vasopressor and/or inotropic medication (If the systolic blood pressure is recovering during the inclusion window of 180 minutes the patient may be included)
• Use of intra-aortic balloon pump/axial flow device/ECMO (If the patient is weaned and the device is removed during the inclusion window of 180 minutes the patient may be included)
• Temperature on admission <30°C
• Known allergy for dexamethasone or olanzapine
• Ongoing (within 48 h) treatment with olanzapine or dexamethasone
• Known back or hip condition that precluded the patients from being positioned with backrest from 0 to 45-degree angle
• Known or suspected Long QT Syndrome (LQTS)
• Known active fungal disease. Localized skin lesions do not exclude patients from inclusion
• Estimated body weight <45kg

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with successful wake-up	Defined as awake and successfully extubated.	0-6 hours or 28-36 hours according to DANOHCA randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of intubation	Assessed as the duration of intubation from randomization till extubation during initial ICU stay (oral and tracheostomy combined).	Up to 90 days.
Days alive outside hospital	Counted as days alive outside of hospital after discharge.	30 days.
30-day mortality	Number of patients dying from all causes.	30 days.
90-day mortality	Number of patients dying from all causes.	90 days.
Length of ICU stay	Assessed as the initial ICU length of stay.	From randomization till discharge from the ICU, up to 90 days.
Length of hospital stay	Assessed as the hospital length of stay (including in-patient rehabilitation and transfer to referral hospital).	From randomization till discharge from hospital or in-patient rehabilitation, up to 90 days.
Cerebral Performance Category (CPC)	CPC score at ICU discharge, at hospital discharge, and at ambulatory follow-up (scheduled visit at 3 to 6 months after the cardiac arrest). The CPC score ranges from 1 to 5 with higher scores indicating worse outcomes.	Up to 6 months.
Number of patients with successful delayed wake-up	Defined as awake and successfully extubated later than according to DANOHCA randomization.	Up to 90 days.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark
• Investigators: Study Chair: Christian Hassager, MD, DMSc, Department of Cardiology, Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 13, 2025
• First Submitted That Met QC Criteria: May 13, 2025
• First Posted (Actual): May 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: sedation; wakeup
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Brain Ischemia; Signs and Symptoms, Respiratory; Hypoxia, Brain; Hypoxia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Arrest; Hypoxia-Ischemia, Brain; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Neurological; Radiography; Ultrasonography; Echoencephalography; Neuroradiography; Neuroimaging; Ultrasonography, Doppler; Ultrasonography, Doppler, Transcranial
• Other Study ID Numbers: 26745886; H-21077461 (Other Identifier: Capital Region Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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