Consciousness DisordersCyDoC-MAPNCT07736820
Multimodal Assessment and Prognosis in Disorders of Consciousness After Severe Brain Injury (CyDoC-MAP)
An observational study of Consciousness Disorders and Persistent Vegetative State, run by Nicosia General Hospital at 1 site in Cyprus.
Trial summary
After a severe brain injury some patients survive but cannot communicate, and deciding early which of them are likely to recover consciousness remains one of the hardest problems in neurocritical care. Bedside examination alone misclassifies a substantial proportion of these patients. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Consciousness Disorders, Persistent Vegetative State, Unresponsive Wakefulness Syndrome
- How many people
- 40 participants
- Where
- 1 siteCyprus
- Study dates
- 15 Sep 2026to 30 Sep 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Consecutive patients aged 16 years or older admitted or transferred to Nicosia General Hospital with a disorder of consciousness following moderate-to-severe traumatic brain injury or haemorrhagic stroke, who required intubation within 24 hours of the index event and who are classified as VS/UWS or MCS on the Coma Recovery Scale-Revised.
Who may be able to join
- Age 16 years or older
- Moderate-to-severe traumatic brain injury, or haemorrhagic stroke (intracerebral or subarachnoid haemorrhage)
- Intubation for a reduced level of consciousness within 24 hours of the index event
- Admitted to, or transferred to, Nicosia General Hospital
- Classified as VS/UWS or MCS on the Coma Recovery Scale-Revised after discharge from the intensive care unit
- Written informed consent obtained from the next of kin (and from a legal guardian for participants aged 16-17)
Who cannot join
- Severe pre-existing psychiatric disorder
- History of ischaemic or haemorrhagic stroke
- Pre-existing dementia
- Reduction in Glasgow Coma Scale attributable to sedation or intoxicating substances
- Reduction in Glasgow Coma Scale attributable to severe extracranial injury (massive haemorrhage, generalised hypoxia)
- End-stage disease with a life expectancy of less than 6 months
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Iakovos Lytrides, MD MSc contact
Cyprus1 site
Nicosia General Hospital, Department of Neurosurgery
Nicosia, 2029
Constantinos Picolas, +357 22603494, c.picolas@shso.org.cy
About this study
Official title: Cyprus Disorders of Consciousness - Multimodal Assessment and Prognosis Study: A Single-Centre Prospective Observational Cohort Study of Clinical, Biochemical, Electrophysiological and Imaging Predictors of Long-Term Outcome After Severe Traumatic Brain Injury or Haemorrhagic Stroke
After a severe brain injury some patients survive but cannot communicate, and deciding early which of them are likely to recover consciousness remains one of the hardest problems in neurocritical care. Bedside examination alone misclassifies a substantial proportion of these patients.
CyDoC-MAP is a single-centre, prospective, observational cohort study conducted at Nicosia General Hospital, the sole trauma referral centre for Cyprus. It enrols patients aged 16 years or older who are intubated within 24 hours of a moderate-to-severe traumatic brain injury or a haemorrhagic stroke (intracerebral or subarachnoid haemorrhage), and who are subsequently classified as being in a vegetative state / unresponsive wakefulness syndrome (VS/UWS) or a minimally conscious state (MCS) on the Coma Recovery Scale-Revised (CRS-R).
Read more
Four assessment modalities are recorded: (1) the CRS-R, performed at least twice with an interval of at least 48 hours; (2) serum neuron-specific enolase (NSE) sampled within 24 hours of intubation; (3) the bispectral index (BIS), recorded at least twice with an interval of at least 48 hours, after five minutes of standardised noxious and auditory stimulation; and (4) in the traumatic subgroup only, 1.5 T magnetic resonance imaging performed 7-28 days after injury and graded 1-4 by lesion depth by two independent raters.
Level of consciousness is reassessed with the CRS-R 6 to 12 months after the index event, and the total CRS-R score (0-23) at that reassessment is the primary outcome. The primary aim is to estimate the strength of the association between the bispectral index recorded on the ward and that later CRS-R score, and to quantify what the bispectral index adds beyond the baseline clinical assessment. The number of eligible patients at a single national centre does not support the development of a prognostic model; the study is designed to produce effect-size estimates with confidence intervals that will inform a subsequent multicentre study.
The study is purely observational. No intervention is administered, no study procedure alters clinical management, and transfer to rehabilitation is never delayed for research purposes.
Read the detailed description
Background. Functional neuroimaging has shown that a proportion of patients who meet the clinical criteria for a vegetative state retain detectable, volitional brain responses to command - the phenomenon of cognitive motor dissociation (CMD). A recent multicentre study reported CMD in approximately one quarter of behaviourally unresponsive patients, with marked variation between centres. Cyprus has no established diagnostic pathway for disorders of consciousness and no locally available specialised rehabilitation service for this population.
Design. Single-centre, prospective, observational cohort study. No randomisation and no intervention. Patients are identified in the intensive care unit and formally entered into the study once they are transferred to the Neurosurgical or Neurological ward and a disorder of consciousness is documented with the CRS-R. The single exception to this sequence is the NSE biomarker, for which venous blood is drawn within 24 hours of intubation.
Assessment schedule. Step 1 - Enrolment and screening: patients aged 16 years or older with traumatic brain injury or haemorrhagic stroke, intubated for a disorder of consciousness within 24 hours of the event; exclusion criteria applied. Step 2 - Acute phase (ICU, within 24 hours of intubation): venous sample for serum neuron-specific enolase. Step 3 - Ward baseline: CRS-R and BIS, each at least twice with an interval of at least 48 hours; classification as VS/UWS or MCS. BIS is recorded after five minutes of noxious and auditory stimulation to avoid falsely low values due to drowsiness; the highest value is recorded. The CRS-R is administered by the study neurologist or speech and language therapist, with attention to sedation, sepsis, subclinical seizures and environmental confounders; the highest score is recorded. Step 4 - Subacute phase (7-28 days after injury, traumatic subgroup only): 1.5 T MRI with T2/FLAIR, DWI, T2*GRE and SWI sequences; lesions graded 1-4 by depth (cortex / white matter; corpus callosum, basal ganglia, thalamus; brainstem; substantia nigra / mesencephalic tegmentum) by two independent raters, with disagreements resolved by consensus. The timing allows postoperative changes to resolve and intracranial pressure to stabilise. Step 5 - Follow-up (6-12 months after the index event): reassessment with the CRS-R; outcome classified as VS/UWS, MCS or eMCS.
Statistical analysis. The analysis is pre-specified in a signed Statistical Analysis Plan (SAP-01) dated before the enrolment of the first patient. The primary outcome is the total CRS-R score (0-23) at 6-12 months, treated as a continuous variable; the VS/UWS-MCS-eMCS classification is retained as a secondary outcome. The highest bispectral index value is designated in advance as the primary prognostic marker, because it is the novel element of the study and the only marker whose measurement is guaranteed in every enrolled patient. The single hypothesis test is the Spearman rank correlation between the highest bispectral index and the total CRS-R score at follow-up, reported with a 95% confidence interval, alongside a simple linear regression estimating the slope. One secondary pre-specified analysis adds the baseline total CRS-R as a second predictor and reports the incremental explained variance; no further predictor enters that model. Serum neuron-specific enolase, MRI lesion depth grade, age, pre-intubation Glasgow Coma Scale and intensive care length of stay are analysed on an exploratory basis only, without correction for multiple comparisons and without conclusions. The anatomical distribution of MRI lesions is presented descriptively, by site and side, with no significance testing. Inter-rater reliability of the MRI grading is expressed as weighted Kappa. Development of a multivariable prognostic model, stepwise or automated variable selection, searching for an optimal bispectral index cut-off, and dichotomisation of continuous variables are excluded at the outset: with 30-40 patients and an expected 10-18 outcome events, current sample-size criteria for prediction-model development require approximately 320-385 patients. The study is therefore reported as a study of prognostic associations and feasibility, not as prognostic model development.
Ethics and data protection. Approved unanimously by the Cyprus National Bioethics Committee (protocol EEBK/EP 2025/47) on 10 July 2026. Written informed consent is obtained from the next of kin. Data are pseudonymised at the point of collection; no names or direct identifiers are held in the study database. Data handling complies with the EU General Data Protection Regulation, and records are retained for eight years from the start of the study and are then destroyed.
- Conditions
- Consciousness Disorders, Persistent Vegetative State, Unresponsive Wakefulness Syndrome, Minimally Conscious State, Coma; Prolonged, Brain Injuries, Traumatic
- Keywords
- cognitive motor dissociation, covert consciousness, Coma Recovery Scale-Revised, bispectral index, neuron-specific enolase, multimodal prognostication, neurocritical care, Cyprus
- Medical subject headings
- Consciousness Disorders, Persistent Vegetative State, Coma, Brain Injuries, Traumatic, Cerebral Hemorrhage, Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| VS/UWS | Patients classified as being in a vegetative state / unresponsive wakefulness syndrome on the Coma Recovery Scale-Revised at ward baseline. | |
| MCS | Patients classified as being in a minimally conscious state (MCS- or MCS+) on the Coma Recovery Scale-Revised at ward baseline. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Coma Recovery Scale-Revised (CRS-R) score at 6-12 months
Total score on the Coma Recovery Scale-Revised at the 6-12 month reassessment, treated as a continuous variable. The CRS-R comprises six subscales (auditory, visual, motor, oromotor/verbal, communication and arousal); the total score ranges from 0 (worst) to 23 (best). The pre-specified primary analysis is the Spearman rank correlation between this score and the highest bispectral index value recorded at ward baseline, reported with a 95% confidence interval. Death before follow-up is reported separately and is not coded as a score of 0 in the primary analysis; a pre-specified sensitivity analysis assigns a value of 0 to those who died.
Measured: 6 to 12 months after the index event
Secondary outcomes (6)
CRS-R diagnostic category at 6-12 months
Classification derived from the Coma Recovery Scale-Revised at follow-up as vegetative state / unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS) or emergence from the minimally conscious state (eMCS) - the clinically legible form of the primary outcome. Transitions between the ward baseline category and the follow-up category are presented descriptively, including the proportion of patients classified as VS/UWS at baseline who reach MCS or eMCS.
Measured: Ward baseline to 6-12 months
Serum neuron-specific enolase (NSE) - exploratory
Correlation between the serum NSE concentration (microgram/L) obtained within 24 hours of intubation and the total CRS-R score at follow-up, with a 95% confidence interval. Exploratory only: no correction for multiple comparisons is applied and no conclusion is drawn. The assay is not guaranteed in every enrolled patient, so the number of available observations is stated in every related table.
Measured: Within 24 hours of intubation to 6-12 months
Incremental value of the bispectral index beyond the baseline clinical assessment
Incremental explained variance (delta R-squared), with a confidence interval, from a linear regression of the total CRS-R score at follow-up on two predictors only: the highest bispectral index value and the baseline total CRS-R score. No further predictor enters this model. The analysis is stated in advance to be underpowered - an incremental contribution of the order of 15% is detectable at the anticipated sample size, whereas 10% is not - and a negative result will not be interpreted as evidence of absence of effect.
Measured: Ward baseline to 6-12 months
MRI lesion depth grade, traumatic subgroup - exploratory
Correlation between the 1-4 lesion depth grade on 1.5 T MRI obtained 7-28 days after injury and the total CRS-R score at follow-up, in patients with traumatic brain injury (anticipated approximately 20). Exploratory only, without correction for multiple comparisons. In the non-traumatic group these data are characterised as structurally not applicable rather than missing, since MRI is performed by design only after trauma.
Measured: 7-28 days after injury to 6-12 months
Anatomical distribution of MRI lesions - descriptive only
Presence and side (right, left or bilateral) of lesions at seven anatomical sites - cerebral cortex or lobar white matter, corpus callosum, basal ganglia, thalamus, brainstem (pons, medulla, cerebral peduncles), substantia nigra and midbrain tegmentum - recorded by consensus of the two raters. Presented as a per-patient table and as frequencies per site cross-tabulated with outcome category. Explicitly descriptive: no p-values, no chi-square or Fisher test, and no claim of association. The 1-4 grade is hierarchical and retains only the deepest lesion, so site-by-site recording preserves information that would otherwise be lost at the moment the form is completed.
Measured: 7-28 days after injury to 6-12 months
Inter-rater reliability of MRI lesion depth grading
Agreement between the two independent raters on the 1-4 lesion depth grade, expressed as a linearly weighted Kappa given the ordinal nature of the grade, with disagreements resolved by consensus. Where independent duplicate CRS-R assessments exist, the intraclass correlation coefficient for the total score is also reported. Both with 95% confidence intervals.
Measured: 7-28 days after injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2026
- Study start15 Sep 2026 (estimated)
- Primary completion15 Sep 2030 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Consciousness DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicosia General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Constantinos Picolas, MD MA, Nicosia General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07736820
- Sponsor's protocol ID
- CyDoC-MAP-2025-47
- Other IDs
- EEBK/EP 2025/47
- Acronym
- CyDoC-MAP
- Status last verified
- Jul 2026
- First submitted
- 27 Jul 2026
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: A decision on sharing individual participant data will be made after the primary publication. The cohort is small and is drawn from the single national referral centre of a small population, so any sharing would first require an assessment of the residual risk of re-identification. The approved informed-consent documents do not currently cover onward sharing of individual-level data. Data are held pseudonymised and are destroyed eight years after the start of the study.
Publications
Kondziella D. The Gray Zone of Consciousness: Cognitive Motor Dissociation. Curr Neurol Neurosci Rep. 2025 Jul 18;25(1):49. doi: 10.1007/s11910-025-01438-2.
PubMed 40679720Bodien YG, Allanson J, Cardone P, Bonhomme A, Carmona J, Chatelle C, Chennu S, Conte M, Dehaene S, Finoia P, Heinonen G, Hersh JE, Kamau E, Lawrence PK, Lupson VC, Meydan A, Rohaut B, Sanders WR, Sitt JD, Soddu A, Valente M, Velazquez A, Voss HU, Vrosgou A, Claassen J, Edlow BL, Fins JJ, Gosseries O, Laureys S, Menon D, Naccache L, Owen AM, Pickard J, Stamatakis EA, Thibaut A, Victor JD, Giacino JT, Bagiella E, Schiff ND. Cognitive Motor Dissociation in Disorders of Consciousness. N Engl J Med. 2024 Aug 15;391(7):598-608. doi: 10.1056/NEJMoa2400645.
PubMed 39141852Schnakers C, Ledoux D, Majerus S, Damas P, Damas F, Lambermont B, Lamy M, Boly M, Vanhaudenhuyse A, Moonen G, Laureys S. Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders. Brain Inj. 2008 Nov;22(12):926-31. doi: 10.1080/02699050802530565.
PubMed 19005884Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006 Sep 8;313(5792):1402. doi: 10.1126/science.1130197.
PubMed 16959998Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.
PubMed 15605342
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyprus Disorders of Consciousness - Multimodal Assessment and Prognosis Study: A Single-Centre Prospective Observational Cohort Study of Clinical, Biochemical, Electrophysiological and Imaging Predictors of Long-Term Outcome After Severe Traumatic Brain Injury or Haemorrhagic Stroke
- ClinicalTrials.gov ID
- NCT07736820
- Acronym / sponsor ID
- CyDoC-MAP / CyDoC-MAP-2025-47
- Conditions
- Consciousness Disorders, Persistent Vegetative State, Unresponsive Wakefulness Syndrome, Minimally Conscious State, Coma; Prolonged, Brain Injuries, Traumatic
- Keywords
- cognitive motor dissociation, covert consciousness, Coma Recovery Scale-Revised, bispectral index, neuron-specific enolase, multimodal prognostication, neurocritical care, Cyprus
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Nicosia General HospitalUniversity, hospital or other
- Study start
- 15 Sep 2026 (estimated)
- Primary completion
- 15 Sep 2030 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 30 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
After a severe brain injury some patients survive but cannot communicate, and deciding early which of them are likely to recover consciousness remains one of the hardest problems in neurocritical care. Bedside examination alone misclassifies a substantial proportion of these patients.
CyDoC-MAP is a single-centre, prospective, observational cohort study conducted at Nicosia General Hospital, the sole trauma referral centre for Cyprus. It enrols patients aged 16 years or older who are intubated within 24 hours of a moderate-to-severe traumatic brain injury or a haemorrhagic stroke (intracerebral or subarachnoid haemorrhage), and who are subsequently classified as being in a vegetative state / unresponsive wakefulness syndrome (VS/UWS) or a minimally conscious state (MCS) on the Coma Recovery Scale-Revised (CRS-R).
Four assessment modalities are recorded: (1) the CRS-R, performed at least twice with an interval of at least 48 hours; (2) serum neuron-specific enolase (NSE) sampled within 24 hours of intubation; (3) the bispectral index (BIS), recorded at least twice with an interval of at least 48 hours, after five minutes of standardised noxious and auditory stimulation; and (4) in the traumatic subgroup only, 1.5 T magnetic resonance imaging performed 7-28 days after injury and graded 1-4 by lesion depth by two independent raters.
Level of consciousness is reassessed with the CRS-R 6 to 12 months after the index event, and the total CRS-R score (0-23) at that reassessment is the primary outcome. The primary aim is to estimate the strength of the association between the bispectral index recorded on the ward and that later CRS-R score, and to quantify what the bispectral index adds beyond the baseline clinical assessment. The number of eligible patients at a single national centre does not support the development of a prognostic model; the study is designed to produce effect-size estimates with confidence intervals that will inform a subsequent multicentre study.
The study is purely observational. No intervention is administered, no study procedure alters clinical management, and transfer to rehabilitation is never delayed for research purposes.
Detailed description
Background. Functional neuroimaging has shown that a proportion of patients who meet the clinical criteria for a vegetative state retain detectable, volitional brain responses to command - the phenomenon of cognitive motor dissociation (CMD). A recent multicentre study reported CMD in approximately one quarter of behaviourally unresponsive patients, with marked variation between centres. Cyprus has no established diagnostic pathway for disorders of consciousness and no locally available specialised rehabilitation service for this population.
Design. Single-centre, prospective, observational cohort study. No randomisation and no intervention. Patients are identified in the intensive care unit and formally entered into the study once they are transferred to the Neurosurgical or Neurological ward and a disorder of consciousness is documented with the CRS-R. The single exception to this sequence is the NSE biomarker, for which venous blood is drawn within 24 hours of intubation.
Assessment schedule. Step 1 - Enrolment and screening: patients aged 16 years or older with traumatic brain injury or haemorrhagic stroke, intubated for a disorder of consciousness within 24 hours of the event; exclusion criteria applied. Step 2 - Acute phase (ICU, within 24 hours of intubation): venous sample for serum neuron-specific enolase. Step 3 - Ward baseline: CRS-R and BIS, each at least twice with an interval of at least 48 hours; classification as VS/UWS or MCS. BIS is recorded after five minutes of noxious and auditory stimulation to avoid falsely low values due to drowsiness; the highest value is recorded. The CRS-R is administered by the study neurologist or speech and language therapist, with attention to sedation, sepsis, subclinical seizures and environmental confounders; the highest score is recorded. Step 4 - Subacute phase (7-28 days after injury, traumatic subgroup only): 1.5 T MRI with T2/FLAIR, DWI, T2*GRE and SWI sequences; lesions graded 1-4 by depth (cortex / white matter; corpus callosum, basal ganglia, thalamus; brainstem; substantia nigra / mesencephalic tegmentum) by two independent raters, with disagreements resolved by consensus. The timing allows postoperative changes to resolve and intracranial pressure to stabilise. Step 5 - Follow-up (6-12 months after the index event): reassessment with the CRS-R; outcome classified as VS/UWS, MCS or eMCS.
Statistical analysis. The analysis is pre-specified in a signed Statistical Analysis Plan (SAP-01) dated before the enrolment of the first patient. The primary outcome is the total CRS-R score (0-23) at 6-12 months, treated as a continuous variable; the VS/UWS-MCS-eMCS classification is retained as a secondary outcome. The highest bispectral index value is designated in advance as the primary prognostic marker, because it is the novel element of the study and the only marker whose measurement is guaranteed in every enrolled patient. The single hypothesis test is the Spearman rank correlation between the highest bispectral index and the total CRS-R score at follow-up, reported with a 95% confidence interval, alongside a simple linear regression estimating the slope. One secondary pre-specified analysis adds the baseline total CRS-R as a second predictor and reports the incremental explained variance; no further predictor enters that model. Serum neuron-specific enolase, MRI lesion depth grade, age, pre-intubation Glasgow Coma Scale and intensive care length of stay are analysed on an exploratory basis only, without correction for multiple comparisons and without conclusions. The anatomical distribution of MRI lesions is presented descriptively, by site and side, with no significance testing. Inter-rater reliability of the MRI grading is expressed as weighted Kappa. Development of a multivariable prognostic model, stepwise or automated variable selection, searching for an optimal bispectral index cut-off, and dichotomisation of continuous variables are excluded at the outset: with 30-40 patients and an expected 10-18 outcome events, current sample-size criteria for prediction-model development require approximately 320-385 patients. The study is therefore reported as a study of prognostic associations and feasibility, not as prognostic model development.
Ethics and data protection. Approved unanimously by the Cyprus National Bioethics Committee (protocol EEBK/EP 2025/47) on 10 July 2026. Written informed consent is obtained from the next of kin. Data are pseudonymised at the point of collection; no names or direct identifiers are held in the study database. Data handling complies with the EU General Data Protection Regulation, and records are retained for eight years from the start of the study and are then destroyed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VS/UWS | – | –Patients classified as being in a vegetative state / unresponsive wakefulness syndrome on the Coma Recovery Scale-Revised at ward baseline. |
| MCS | – | –Patients classified as being in a minimally conscious state (MCS- or MCS+) on the Coma Recovery Scale-Revised at ward baseline. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Consecutive patients aged 16 years or older admitted or transferred to Nicosia General Hospital with a disorder of consciousness following moderate-to-severe traumatic brain injury or haemorrhagic stroke, who required intubation within 24 hours of the index event and who are classified as VS/UWS or MCS on the Coma Recovery Scale-Revised.
Key inclusion criteria (6 listed)
- Age 16 years or older
- Moderate-to-severe traumatic brain injury, or haemorrhagic stroke (intracerebral or subarachnoid haemorrhage)
- Intubation for a reduced level of consciousness within 24 hours of the index event
- Admitted to, or transferred to, Nicosia General Hospital
- Classified as VS/UWS or MCS on the Coma Recovery Scale-Revised after discharge from the intensive care unit
Key exclusion criteria (6 listed)
- Severe pre-existing psychiatric disorder
- History of ischaemic or haemorrhagic stroke
- Pre-existing dementia
- Reduction in Glasgow Coma Scale attributable to sedation or intoxicating substances
- Reduction in Glasgow Coma Scale attributable to severe extracranial injury (massive haemorrhage, generalised hypoxia)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Total Coma Recovery Scale-Revised (CRS-R) score at 6-12 months
Time frame: 6 to 12 months after the index event
Total score on the Coma Recovery Scale-Revised at the 6-12 month reassessment, treated as a continuous variable. The CRS-R comprises six subscales (auditory, visual, motor, oromotor/verbal, communication and arousal); the total score ranges from 0 (worst) to 23 (best). The pre-specified primary analysis is the Spearman rank correlation between this score and the highest bispectral index value recorded at ward baseline, reported with a 95% confidence interval. Death before follow-up is reported separately and is not coded as a score of 0 in the primary analysis; a pre-specified sensitivity analysis assigns a value of 0 to those who died.
6 secondary outcomes
CRS-R diagnostic category at 6-12 months
Time frame: Ward baseline to 6-12 months
Serum neuron-specific enolase (NSE) - exploratory
Time frame: Within 24 hours of intubation to 6-12 months
Incremental value of the bispectral index beyond the baseline clinical assessment
Time frame: Ward baseline to 6-12 months
MRI lesion depth grade, traumatic subgroup - exploratory
Time frame: 7-28 days after injury to 6-12 months
Anatomical distribution of MRI lesions - descriptive only
Time frame: 7-28 days after injury to 6-12 months
Inter-rater reliability of MRI lesion depth grading
Time frame: 7-28 days after injury
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Background: PubMed 40679720Kondziella D. The Gray Zone of Consciousness: Cognitive Motor Dissociation. Curr Neurol Neurosci Rep. 2025 Jul 18;25(1):49. doi: 10.1007/s11910-025-01438-2.
- Background: PubMed 39141852Bodien YG, Allanson J, Cardone P, Bonhomme A, Carmona J, Chatelle C, Chennu S, Conte M, Dehaene S, Finoia P, Heinonen G, Hersh JE, Kamau E, Lawrence PK, Lupson VC, Meydan A, Rohaut B, Sanders WR, Sitt JD, Soddu A, Valente M, Velazquez A, Voss HU, Vrosgou A, Claassen J, Edlow BL, Fins JJ, Gosseries O, Laureys S, Menon D, Naccache L, Owen AM, Pickard J, Stamatakis EA, Thibaut A, Victor JD, Giacino JT, Bagiella E, Schiff ND. Cognitive Motor Dissociation in Disorders of Consciousness. N Engl J Med. 2024 Aug 15;391(7):598-608. doi: 10.1056/NEJMoa2400645.
- Background: PubMed 19005884Schnakers C, Ledoux D, Majerus S, Damas P, Damas F, Lambermont B, Lamy M, Boly M, Vanhaudenhuyse A, Moonen G, Laureys S. Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders. Brain Inj. 2008 Nov;22(12):926-31. doi: 10.1080/02699050802530565.
- Background: PubMed 16959998Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006 Sep 8;313(5792):1402. doi: 10.1126/science.1130197.
- Background: PubMed 15605342Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.
- Study website (Greek and English)Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided. A decision on sharing individual participant data will be made after the primary publication. The cohort is small and is drawn from the single national referral centre of a small population, so any sharing would first require an assessment of the residual risk of re-identification. The approved informed-consent documents do not currently cover onward sharing of individual-level data. Data are held pseudonymised and are destroyed eight years after the start of the study.
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Prolonged Disorders of Consciousness, Tracheostomy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Iakovos Lytrides, MD MSc contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Consciousness Disorders and Persistent Vegetative State, run by Nicosia General Hospital at 1 site in Cyprus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Constantinos Picolas, MD MA (+357 22603494, c.picolas@shso.org.cy), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Coma Recovery Scale-Revised (CRS-R) score at 6-12 months (time frame: 6 to 12 months after the index event). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07736820, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.