Improving Diagnosis and Prediction of Outcome in Patients With Severe Disorders of Consciousness (IMPROVE-DOC)

Patients with acute severe brain injury are usually admitted to the Intensive Care Unit. A substantial proportion of these patients will have disorders of consciousness (DOC) after interruption of sedation. It is difficult to reliably predict neurological outcome in these patients. Dependent on the extent of permanently damaged brain areas, DOC in patients with acute severe brain injury may improve or persist, eventually evolving into a minimal conscious state (MCS) or unresponsive wakefulness syndrome (UWS). These conditions are accompanied by long term severe disability. In current practice, the decision to withdraw life-sustaining support is made by interpreting the results of repeated bedside neurological examination and conventional CT-brain imaging. Reliable identification of patients with a possible good outcome, in whom treatment should not be withdrawn, is difficult. In this prospective observational cohort study we aim to identify patients with a good neurological outcome.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Encephalitis; Traumatic Brain Injury; Meningitis; Intracranial Hemorrhages; Subarachnoid Hemorrhage

Detailed Description

In order to identify patients with a good neurological outcome a combination of diagnostic tests is used.

Clinical rating scales

• Simplified evaluation of consciousness scale (SECONDs) and the full outline of unresponsiveness (FOUR) score
• Once a week

Blood biomarkers

• Neuron specific enolase, neurofilament light, glial fibrillary acidic protein
• Sampling timepoints: 24h, 72h, 7 days and 14 days after brain injury
• Serum (STG-5) and plasma (EDTA-6) tubes, aliquoted (4 x 0.5ml) and stored at -80°C

EEG with reactivity testing

• Standard 21-electrode montage

• Stimuli protocol I: a set of 5 stimuli repeated 3 times

  1. Auditory: clapping in hands, 2. Auditory: calling patients name loudly, 3. Visual: passive eye opening, 4. Tactile: nasal tickle, 5. Noxious: sternal rub Each stimuli is applied for a duration of 5 seconds and an interval between stimuli of 30 seconds

• Stimuli protocol II: Cognitive-motor dissociation test

MRI-scan

• Sequences considered essential for patient care i.e.T1, T2, FLAIR, DWI/SWI
• Preferably, performed between 4-6 weeks after hospital admission

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Wolmet Haksteen, MD; Phone Number: +31 020 566 9111; Email: w.e.haksteen@amsterdamumc.nl
• Study Contact Backup: Name: Janneke Horn, Prof. dr.; Email: j.horn@amsterdamumc.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Not yet recruiting
    • UMC Groningen
    • Contact: Joukje van der Naalt
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboud UMC
      • Contact: Astrid Hoedemaekers
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC
      • Contact: Wolmet Haksteen, MD; Phone Number: +31 020 - 566 9111; Email: w.e.haksteen@amsterdamumc.nl
  • Zuid-Holland
    • Den Haag, Zuid-Holland, Netherlands, 2512 VA
      • Recruiting
      • Haaglanden MC, locatie Westeinde
      • Contact: Sefanja Achterberg
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Not yet recruiting
      • Erasmus MC
      • Contact: Mathieu van der Jagt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All patients with acute severe brain injury admitted to the ICU of at least 18 years old.

Description

Inclusion Criteria:

All patients that are admitted to the ICU with the following criteria will be eligible for inclusion:

1. Severe brain injury (GCS ≤ 8) as a result of:

   1. Traumatic brain injury
   2. Ischemic cerebrovascular accident
   3. Intracranial hemorrhage
   4. Meningo-encephalitis
   5. Subarachnoid hemorrhage
2. Age ≥ 18 years old
3. Written informed consent from legal representatives

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Absence of informed consent
• Moribund at ICU admission
• Progressive neurodegenerative disease
• Pre-admission life expectancy ≤ 6 months based on comorbidity
• GCS has been > 8 prior to inclusion
• Impossible to include within 24 hours after brain injury

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glasgow Outcome Scale Extended	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Glasgow Outcome Scale Extended	12 months

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: February 22, 2024
• First Posted (Estimated): February 28, 2024

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Neuroinflammatory Diseases; Encephalitis; Brain Injuries; Hemorrhage; Brain Injuries, Traumatic; Meningitis; Intracranial Hemorrhages; Subarachnoid Hemorrhage; Consciousness Disorders
• Other Study ID Numbers: NL82013.018.22

Drug and device information, study documents

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