Intracerebral HemorrhageCR-4-HealthNCT07882784
Outcome Prediction and Recovery After Spontaneous Intracerebral Haemorrhage
An observational study of Intracerebral Hemorrhage and Hemorrhagic Stroke, run by University Medical Centre Maribor at 3 sites in 2 countries.
Trial summary
Spontaneous intracerebral haemorrhage (ICH) is a severe form of stroke with high mortality and frequent long-term disability. Current tools to predict how an individual patient will recover are limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracerebral Hemorrhage, Hemorrhagic Stroke
- How many people
- 300 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 1 Nov 2026to 31 Oct 2028
- Phase
- Observational
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive adults with acute spontaneous (non-traumatic) intracerebral haemorrhage admitted to stroke units, neurology wards, neurosurgical units or intensive care units of three hospital centres in Slovenia and Austria.
Who may be able to join
- Age 18 years or older
- Acute spontaneous (non-traumatic) intracerebral haemorrhage confirmed by non-contrast CT or MRI
- Admission during the acute phase of haemorrhage to one of the participating centres
- Written informed consent from the patient or, if the patient lacks capacity, consent from a legally authorised representative
Who cannot join
- Intracerebral haemorrhage secondary to head trauma
- Haemorrhage due to an intracranial neoplasm
- Isolated subarachnoid haemorrhage or another primary type of intracranial haemorrhage
- Expected survival of less than 24 hours due to non-neurological comorbidity
- End-of-life care decision already made at presentation
- Withdrawal of consent or major protocol violation
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Austria2 sites
LKH-Universitätsklinikum Graz, Medical University of Graz
Graz, 8036
Klinikum Klagenfurt am Wörthersee
Klagenfurt, 9020
Slovenia1 site
University Medical Centre Maribor, Department of Neurology
Maribor, 2000
About this study
Official title: CrossReg-4-Health: A Multicentre Prospective Cohort Study of Outcome Prediction and Recovery After Spontaneous Intracerebral Haemorrhage
Spontaneous intracerebral haemorrhage (ICH) is a severe form of stroke with high mortality and frequent long-term disability. Current tools to predict how an individual patient will recover are limited.
CrossReg-4-Health is a prospective, multicentre observational cohort study that will enrol 300 consecutive adults with acute spontaneous ICH at three hospitals in Slovenia and Austria. During hospitalisation, the study will collect clinical data, standardised neurological and pain assessments, routine laboratory results, CT, CT angiography and MRI findings, and two research blood samples for biomarkers of brain injury, inflammation, coagulation and pain. Participants will be followed up at 6 and 12 months for survival, functional outcome, neurological status, pain, health-related quality of life, rehabilitation use and readmissions.
The main aim is to develop a multimodal prognostic model for functional outcome (modified Rankin Scale) 12 months after ICH.
Read the detailed description
Background: Outcome prediction after spontaneous intracerebral haemorrhage (ICH) relies mainly on clinical severity and neuroimaging markers and only partially captures multidimensional recovery. Blood-based biomarkers, pain burden, rehabilitation exposure, care trajectories and patient-reported outcomes are rarely integrated in prospective real-world cohorts.
Design: Prospective, multicentre, longitudinal observational cohort study conducted within the Interreg Slovenia-Austria project CrossReg-4-Health (grant SIAT00307). Approximately 100 consecutive patients will be enrolled at each of three centres (University Medical Centre Maribor; LKH-Universitätsklinikum Graz; Klinikum Klagenfurt am Wörthersee). Treatment follows routine clinical practice and is not influenced by study participation.
Assessments:
- Admission: demographics, vascular risk factors, comorbidities, medication (including antithrombotic treatment), premorbid mRS, NIHSS, GCS, baseline non-contrast CT (NCCT), routine laboratory tests, first research blood sample.
- Approximately 24-48 hours: repeat NCCT for haematoma expansion, repeat NIHSS, second research blood sample where feasible.
- During hospitalisation: hierarchical pain assessment (NRS 0-10 in communicative patients; Behavioural Pain Scale in ventilated or non-communicative patients; revised Nociception Coma Scale in disorders of consciousness; PAIC15 or Doloplus-2 in aphasia or cognitive impairment), MRI when clinically stable (T2, FLAIR, SWI), care-trajectory data.
- Discharge: NIHSS, mRS, length of stay, discharge destination, rehabilitation plan.
- 6 and 12 months: survival, NIHSS, mRS, pain (NRS), PROMIS-29, EQ-5D VAS, rehabilitation use, readmissions, living status.
Biomarkers: S100B, GFAP, NfL, CRP, IL-6, TNF-alpha, IL-10, D-dimer and exploratory substance P, analysed centrally in batches. Remaining aliquots are stored in the institutional biobank only with separate optional consent.
Neuroimaging: haematoma volume and location, intraventricular haemorrhage, haematoma expansion, perihaematomal oedema, CTA spot sign, CT and MRI markers of cerebral small vessel disease (white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, lacunes, enlarged perivascular spaces) and MRI-based aetiology. CT-based radiomics and premorbid frailty indicators are exploratory.
Statistical analysis: The primary model is multivariable logistic regression for unfavourable outcome (mRS 4-6 vs 0-3) at 12 months with approximately 15 prespecified candidate predictor parameters (sample size checked using the Riley framework: outcome proportion 0.55, anticipated Cox-Snell R2 0.25, target shrinkage 0.90). Penalised regression may be used. Performance will be assessed by discrimination, calibration and overall performance, with internal validation by bootstrapping or cross-validation. The full ordinal mRS will be analysed with proportional odds regression as a secondary analysis. Mortality will be analysed with Kaplan-Meier methods and Cox regression. Missing data will be handled by multiple imputation, with complete-case sensitivity analysis.
Embedded substudy: A subset of up to 100 participants with upper-limb motor impairment will take part in an exploratory rehabilitation substudy of haptic-assisted virtual reality training, registered separately on ClinicalTrials.gov.
- Conditions
- Intracerebral Hemorrhage, Hemorrhagic Stroke
- Keywords
- intracerebral haemorrhage, prognostic model, biomarkers, GFAP, neurofilament light chain, cerebral small vessel disease, post-stroke pain, PROMIS-29, quality of life, care trajectories
- Medical subject headings
- Cerebral Hemorrhage, Hemorrhagic Stroke, Charcot-Marie-Tooth disease, Type 1F, Cerebral Small Vessel Diseases
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 |
|---|---|---|
| Spontaneous ICH cohort | Consecutive adults with acute spontaneous intracerebral haemorrhage admitted to one of three participating centres, managed according to routine clinical practice. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unfavourable functional outcome at 12 months (modified Rankin Scale 4-6)
Proportion of participants with mRS 4-6 (unfavourable) versus 0-3. The mRS ranges from 0 (no symptoms) to 6 (death); higher scores indicate worse outcome. Used as the outcome of the multivariable prognostic model.
Measured: 12 months after ICH onset
Secondary outcomes (15)
Functional outcome on the full ordinal modified Rankin Scale at 12 months
Distribution of mRS scores (0 = no symptoms to 6 = death; higher scores indicate worse outcome), analysed with proportional odds regression.
Measured: 12 months after ICH onset
Functional outcome at 6 months (modified Rankin Scale)
mRS score (0 = no symptoms to 6 = death; higher scores indicate worse outcome).
Measured: 6 months after ICH onset
All-cause mortality
Proportion of participants who died from any cause.
Measured: 30 days, 6 months and 12 months after ICH onset
Change in neurological deficit (NIHSS) during hospitalisation
National Institutes of Health Stroke Scale score (0-42; higher scores indicate more severe deficit).
Measured: Admission, approximately 48 hours, and hospital discharge (up to approximately 4 weeks)
Neurological deficit at follow-up (NIHSS)
National Institutes of Health Stroke Scale score (0-42; higher scores indicate more severe deficit).
Measured: 6 and 12 months after ICH onset
Pain burden during hospitalisation
Pain assessed hierarchically according to communication ability: Numeric Rating Scale 0-10 (higher = more pain) in communicative patients; Behavioural Pain Scale, revised Nociception Coma Scale, PAIC15 or Doloplus-2 in non-communicative patients.
Measured: From admission to hospital discharge (up to approximately 4 weeks)
Pain intensity at follow-up (Numeric Rating Scale)
Numeric Rating Scale 0-10 (0 = no pain, 10 = worst imaginable pain).
Measured: 6 and 12 months after ICH onset
Health-related quality of life (PROMIS-29)
PROMIS-29 domain T-scores (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, pain interference) and pain intensity item. Higher scores indicate more of the domain measured.
Measured: 6 and 12 months after ICH onset
Self-rated health (EQ-5D VAS)
EuroQol visual analogue scale, 0 (worst imaginable health) to 100 (best imaginable health).
Measured: 6 and 12 months after ICH onset
Intensive care unit length of stay
Days in the intensive care unit.
Measured: From admission to hospital discharge (up to approximately 4 weeks)
ICU-to-ward transition time
Time from admission to transfer from the intensive care unit to a ward, in days.
Measured: From admission to hospital discharge (up to approximately 4 weeks)
Total hospital length of stay
Days from admission to discharge.
Measured: From admission to hospital discharge (up to approximately 4 weeks)
Discharge destination
Categories such as home, inpatient rehabilitation, long-term care facility, other hospital, or death.
Measured: At hospital discharge (up to approximately 4 weeks)
Rehabilitation exposure
Type, setting and amount of rehabilitation received.
Measured: From admission to 12 months after ICH onset
Hospital readmissions
Number of participants readmitted and number of readmissions.
Measured: Up to 12 months after ICH onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Oct 2028 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracerebral HemorrhageStudies 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
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Maribor
- Sponsor type
- University, hospital or other
- Collaborators
- Medical University of Graz, Kärntner Landeskrankenanstalten-Betriebsgesellschaft (KABEG)
- Responsible party
- Sponsor
- Investigators
- Martin Rakuša, MD, PhD, Principal investigator, University Medical Centre Maribor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07882784
- Sponsor's protocol ID
- CrossReg for Health-COHORT
- Other IDs
- SIAT00307
- Acronym
- CR-4-Health
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No, due to legal restrictions.