Predictive Outcome in Comatose Patients (PRECOM)

New Predictive Tool of Awakening in Comatose Patients in the Intensive Care Unit

Evaluating the prognosis of comatose patients after cardiac arrest (CA) in the intensive care unit (ICU) remains challenging. It requires a multimodal approach combining standardized clinical examination, serum biomarkers, imaging and classically electrophysiological examinations, (among them auditive evoked potentials or AEP) but none has a sufficient sensitivity/specificity. In a preliminary study, the investigators developed an algorithm from the signal collected with AEP, and generated a probability map to visually classify the participants after the algorithm processing. Participants could be classified either with a good neurological prognosis or with bad neurological prognosis or death.

The investigators hypothesize that the "PRECOM" tool, applied blindly to a large prospective multicenter cohort of patients admitted to intensive care for coma in the aftermath of CA will predict neurological prognosis at 3 months with high sensitivity and specificity.

Study Overview

• Status: Recruiting
• Conditions: Heart Arrest; Coma; Cardiopulmonary Resuscitation
• Intervention / Treatment: Other: Neurological prognosis

Detailed Description

Evaluating the prognosis of comatose participants after cardiac arrest (CA) in the intensive care unit remains challenging. It requires a multimodal approach combining standardized clinical examination, serum biomarkers, imaging and classically electrophysiological examinations: 1 / the electroencephalogram, bad prognosis assessed when the electroencephalogram (EEG) is discontinuous, areactive, monotone,…), 2 / somesthetic evoked potentials, the absence of the N20 cortical wave has a specificity of poor prognosis of 68-100% and 3 / auditory evoked potentials (AEP), the presence of mismatchnegativity (MMN) would be of good prognosis with a specificity up to 90% but rarely performed in current practice. Routinely, these examinations are sometimes difficult to interpret in sedated participants, in an intensive care unit environment that generates numerous artefacts. Above all, all these techniques require the presence of a neurophysiology unit, with few experts available.

In a preliminary study, in collaboration with the applied mathematics laboratory of the ENS (Ecole Normale Supérieure), an algorithm was developed from the signal extracted from AEP. A probability map was generated with a software allowing to visually classify the participants after processing signal by the algorithm in a cluster of points with a high specificity into "good neurological prognosis" and "bad neurological prognosis". Neither artifacts or sedation prevented data analysis.

The investigators hypothesize that the "PRECOM" tool, applied blindly to a large prospective multicenter cohort of participants admitted to intensive care for coma in the aftermath of a caridiac arrest will predict the neurological prognosis of participants with high sensitivity and specificity. This tool, carried out during the first week of the coma, will be compared to a standardized procedure used routinely by the participating resuscitators.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Nathalie KUBIS, Md, PhD; Phone Number: +33(0)149958324; Email: nathalie.kubis@aphp.fr
• Study Contact Backup: Name: Romain SONNEVILLE, Md, PhD; Phone Number: +33(0)140256139; Email: romain.sonneville@aphp.fr

Study Locations

• France
  • Bobigny, France, 93000
    • Recruiting
    • APHP Avicenne Hospital - Réanimation médico-chirurgicale
    • Contact: Johanna OZIEL, Ph; Phone Number: +33 1 48 95 52 41; Email: johanna.oziel@aphp.fr
    • Principal Investigator: Johanna OZIEL, Ph
  • Paris, France, 75010
    • Active, not recruiting
    • APHP Lariboisière Hospital, Clinical Physiology Department
  • Paris, France, 75010
    • Recruiting
    • APHP Laribosière Hospital - Service de Réanimation Médical et Toxicologique
    • Contact: Bruno MEGARBANE, MD, PhD; Phone Number: +33 (0)1 49 95 64 91; Email: bruno.megarbane@aphp.fr
    • Principal Investigator: Bruno MEGARBANE, Md, PhD
  • Paris, France, 75014
    • Recruiting
    • APHP Cochin Hospital - médecine intensive-réanimation
    • Contact: Sarah BENGHANEM, Ph; Phone Number: +33 1 58 41 25 33; Email: sarah.benghanem@aphp.fr
    • Principal Investigator: Sarah BENGHANEM, Ph
  • Paris, France, 75015
    • Recruiting
    • APHP HEGP hospital - Réanimation médicale
    • Contact: Jean-Luc DIEHL, Md,PhD; Email: jean-luc.diehl@aphp.fr
    • Principal Investigator: Jean-Luc DIEHL, Md,PhD
  • Paris, France, 75018
    • Recruiting
    • APHP Bichat Hospital -Médecine intensive - réanimation infectieuse
    • Contact: Marc DOMAN, Ph; Phone Number: +33 1 40 25 79 24; Email: marc.doman@aphp.fr
    • Principal Investigator: Marc DOMAN, Ph
  • Saint-Denis, France, 93200
    • Recruiting
    • Delafontaine Hospital - médecine intensive-réanimation
    • Contact: Daniel DA SILVA, Md; Email: daniel.silva@ch-stdenis.mssante.fr
    • Principal Investigator: Daniel DA SILVA, Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients admitted to intensive care following a cardica arrest.

Description

Inclusion Criteria:

• Age above18 years old
• Patient affiliated to a French Heath Care Insurance
• Admitted in the intensive care unit (ICU) for coma post extra- or intra-hospital cardiac arrest (CA) with shockable or non-shockable rhythm
• Persistent coma on day 3 after post CA, defined by the inability to respond to a verbal command in an appropriate manner (motor Glasgow components <3 and ocular <3) and at the time of neurophysiological recordings (D3-D7 ± week -end).

Exclusion Criteria:

• Decision to limit resuscitation therapies taken by the resuscitation team
• Inability to perform the auditory evoked potentials (AEP) (deafness, skin lesion or any condition preventing to record AEP).
• Opposition by the trusted person or by the patient once he/she wakes up

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Comatose patients in intensive care unit; Patient admitted in the intensive care unit (ICU) for post cardiac arrest (CA) coma, persistent for at least 3 days after CA.

Other: Neurological prognosis; In usual practice, in intensive care unit, evaluating the neurological prognosis of comatose patients after cardiac arrest requires a multimodal approach combining standardized clinical examination, serum biomarkers, imaging and classically electrophysiological examinations (among them auditive evoked potentials or AEP). An algorithm (PRECOM tool) which has been previously developed from the signal extracted from AEP allows to visually classify the patients after processing signal by the algorithm in a cluster of points with a high specificity into "good neurological prognosis" and "bad neurological prognosis". The AEP signals recorded in the 1st and 2nd week of patient inclusion are to be collected by the neurophysiologist. At the end of the patient's participation in the study, these data will be encrypted, anonymized and transmitted to the mathematician to be processed by the PRECOM tool.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Awakening within 3 months	Awakening is defined as normal motor activity in response to the 3 instructions for the motor component M of the FOUR score (show your thumb, make the V for victory and show your fist; M = 4). This criterion will be collected by the doctor in charge of the patient at the time of the assessment and will be dated.	within 3 months ± 2 weeks after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPC score within 3 months	CPC (Cerebral Performance Category) score is performed wether patient is still hospitalized or returned home. It is performed by phone call if patient returned home. Range of values rates neurological status after cardiac arrest on a scale of 1 to 5 (1 for good cerebral performance up to 5 for brain death).	3 months ± 2 weeks after inclusion
mRS score within 3 months	mRS (Modified Rankin Scale) scores is performed wether patient is still hospitalized or returned home. It is performed by phone call if patient returned home. mRS (modified Rankin Scale) scale measures degree of disability/dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Score can be between 0 (no symptoms at all) and 5 (major disability : bedridden, incontinent and requiring constant nursing care and attention).	3 months ± 2 weeks after inclusion
FOUR score within 3 months	FOUR (Full Outline of UnResponsiveness) score is performed only if patient is still hospitalized (being awake or not). FOUR score is a grading scale for assessing the level of consciousness performed on patients with severe neurologic impairment..It addresses four domains of neurological functioning: Eye response; Motor response ; Brainstem score and Respiratory score. Score is ranging from 0 to 16 where the lower the score, the greater the coma gravity.	3 months ± 2 weeks after inclusion
GOSE score within 3 months	GOSE (Extended Glasgow Outcome Scale) score is performed wether patient is still hospitalized or returned home. GOSE score classifies global outcomes in traumatic brain injury survivors. It rates patient status into one of eight categories ranging from 8 (Upper good recovery) to 1 (Dead).	3 months ± 2 weeks after inclusion
CPC score within 6 months	CPC (Cerebral Performance Category) score is performed wether patient is still hospitalized or returned home. It is performed by phone call if patient returned home. Range of values rates neurological status after cardiac arrest on a scale of 1 to 5 (1 for good cerebral performance up to 5 for brain death).	6 months ± 2 weeks after inclusion
mRS score within 6 months	mRS (Modified Rankin Scale) scores is performed wether patient is still hospitalized or returned home. It is performed by phone call if patient returned home. mRS (modified Rankin Scale) scale measures degree of disability/dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Score can be between 0 (no symptoms at all) and 5 (major disability : bedridden, incontinent and requiring constant nursing care and attention).	within 6 months ± 2 weeks after inclusion
GOSE score within 6 months	GOSE (Extended Glasgow Outcome Scale) score is performed wether patient is still hospitalized or returned home. GOSE score classifies global outcomes in traumatic brain injury survivors. It rates patient status into one of eight categories ranging from 8 (Upper good recovery) to 1 (Dead).	within 6 months ± 2 weeks after inclusion
Awakening within 6 months ± 2 weeks	Awakening is defined as normal motor activity in response to the 3 instructions for the motor component M of the FOUR score (show your thumb, make the V for victory and show your fist; M = 4). This criterion will be collected by the doctor in charge of the patient at the time of the assessment and will be dated. The measurement takes place only if patient is still hospitalized.	within 6 months ± 2 weeks after inclusion
CRS-R score within 6 months	CRS-R (Coma Recovery Scale - Revised) is a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness. The scale is intented to be used to establish diagnosis, monitor behavioral recovery and predict outcome. It is performed only if patient is still hospitalized. The total score ranges between 0 (worst) and 23 (best).	within 6 months ± 2 weeks after inclusion
PRECOM tool - first week of coma	Comparison of the ability of the PRECOM tool using clinical and electrophysiological data at inclusion (the first week of coma), to classify patients with good prognosis, poor prognosis and indeterminate prognosis with respect to this same categorization using the usual evaluation criteria performed routinely by participating resuscitations (clinical examination and EEG for all and evoked potentials in addition for some).	Inclusion visit (3 to 7 days after cardiac arrest +/- 2 days if week-end)
PRECOM tool - second week of coma	Comparison of the ability of the PRECOM tool using clinical and electrophysiological data the second week of coma, to classify patients with good prognosis, poor prognosis and indeterminate prognosis with respect to this same categorization using the usual evaluation criteria performed routinely by participating resuscitations (clinical examination and EEG for all and evoked potentials in addition for some).	One week visit (one week after inclusion visit +/- 2 days)
PRECOM tool - first and second week of coma	Comparison of the ability of the PRECOM tool using combinaison of clinical and electrophysiological data collected both at inclusion and one week later (the first two weeks of coma), to classify patients with good prognosis, poor prognosis and indeterminate prognosis with respect to this same categorization using the usual evaluation criteria performed routinely by participating resuscitations (clinical examination and EEG for all and evoked potentials in addition for some).	Inclusion and one week visits
Awakening - second week of coma	Awakening is defined as normal motor activity in response to the 3 instructions for the motor component M of the FOUR score (show your thumb, make the V for victory and show your fist; M = 4). This criterion will be collected by the doctor in charge of the patient at the time of the assessment and will be dated.	One week visit (one week after inclusion visit +/- 2 days)
NSE blood marker	Comparison of the ability to predict awakening with the PRECOM tool using the NSE blood marker (neuron- spécific enolase) collected 3 days after cardiac arrest between the patients awakened from the coma and those who are not.	3 days post cardiac arrest
Glial blood markor	Comparison of the ability to predict awakening with the PRECOM tool using the Glial Fibrillary Acidic Protein (GFAP) collected at the inclusion visit between the patients awakened from the coma and those who are not.	Inclusion visit (3 to 7 days after cardiac arrest +/- 2 days if week-end)
Neuronal blood markor	Comparison of the ability to predict awakening with the PRECOM tool using the Neurofilament blood marker collected at the inclusion visit between the patients awakened from the coma and those who are not.	Inclusion visit (3 to 7 days after cardiac arrest +/- 2 days if week-end)
Inflammatory blood markor	Comparison of the ability to predict awakening with the PRECOM tool using the inflammatory blood markers : Kynurenine and Tryptophan; collected at the inclusion visit between the patients awakened from the coma and those who are not.	Inclusion visit (3 to 7 days after cardiac arrest +/- 2 days if week-end)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Ecole Normale Supérieure de Paris
• Investigators: Study Director: Nathalie KUBIS, Md,PhD, APHP Lariboisière Hospital, Clinical Physiology Department

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): May 29, 2026

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Prognosis; Classification; Electroencephalography; Algorithms; Somatosensory evoked potentials; Post cardiac arrest for comatose patients; Auditory evoked potentials
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Unconsciousness; Consciousness Disorders; Heart Arrest; Coma
• Other Study ID Numbers: AOR 20045

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