Subarachnoid Haemorrhagic StrokeNCT07129603
Investigation of the Role of Inflammatory Markers in the Early Detection of Cerebral Vasospasm, Delayed Cerebral Ischemia, and Meningitis Associated With External Cerebrospinal Fluid Drainage After Non-Traumatic Subarachnoid Hemorrhage - A Prospective Case-Control Study
An observational study of Subarachnoid Haemorrhagic Stroke, run by Tamas Vegh, MD at 1 site in Hungary.
Trial summary
Background Non-traumatic subarachnoid haemorrhage (SAH) is frequently complicated by delayed cerebral ischaemia (DCI) and by ventriculitis/meningitis when external CSF drains are used; bedside TCCD has limited accuracy for vasospasm detection, creating a need for early biomarkers. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Haemorrhagic Stroke
- How many people
- 100 participants
- Where
- 1 siteHungary
- Study dates
- 1 Aug 2025to 31 Dec 2029
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults (≥18 years) admitted to the Neurosurgical Intensive Care Unit of the University of Debrecen Clinical Centre with non-traumatic subarachnoid haemorrhage (SAH) who, as part of standard care, require external CSF drainage (lumbar or ventricular). Patients are treated per local protocol and monitored with routine severity scales (modified Fisher, Hunt-Hess, WFNS, GCS, VASOGRADE, HAIR). Key exclusions are traumatic SAH, lack of consent, meningitis within the prior 6 months, and clinically relevant immunosuppression. Approximately 100 consecutive eligible patients will be enrolled during the acute hospitalization over the planned inclusion window. The cohort reflects the typical SAH case-mix (both sexes, many critically ill; SAH commonly affects middle-aged adults) and is designed to capture patients at risk for vasospasm, delayed cerebral ischaemia and drain-associated ventriculitis/meningitis under ICU conditions.
Who may be able to join
- Adults (≥18 years).
- Angiography-identifiable non-traumatic SAH (regardless of source).
- Requires lumbar or ventricular drain as part of treatment.
Who cannot join
- Traumatic SAH.
- Patient/legal representative does not consent.
- Meningitis within 6 months prior to ictus.
- Immunosuppressed state (disease or medications affecting WBC number/function).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hungary1 site, 1 recruiting
- Recruiting
University of Debrecen, Department of Anesthesiology and Intensive Care
Debrecen, 4032
Csilla Molnár, MD PhD Full Professor, +36302998097, csmolnar@med.unideb.hu
Dorottya MSzántó, MD, +36309990718, szanto.dorottya@med.unideb.hu
About this study
Background Non-traumatic subarachnoid haemorrhage (SAH) is frequently complicated by delayed cerebral ischaemia (DCI) and by ventriculitis/meningitis when external CSF drains are used; bedside TCCD has limited accuracy for vasospasm detection, creating a need for early biomarkers.
Objective To assess the predictive and diagnostic performance of IL-6, IL-1β, TNFα, procalcitonin (PCT), C-reactive protein (CRP) and adrenomedullin (ADM) measured in CSF and serum for vasospasm, DCI, and drain-associated ventriculitis/meningitis after SAH; to test whether combining biomarkers improves accuracy versus routine parameters; and to explore associations with admission and day-14 serum 25-hydroxy-vitamin D.
Read more
Methods Prospective case-control study at the University of Debrecen (planned n≈100; enrolment 01-Nov-2024-31-Dec-2029). Adults with angiography-verified SAH requiring lumbar/ventricular drainage are included; traumatic SAH, prior 6-month meningitis, and immunosuppression are excluded. TCCD is performed daily for 14 days; suspected vasospasm is defined by mean flow velocity >120 cm/s, severe by >200 cm/s, with monitoring extended to day 21 if severe. Sampling: daily CSF IL-6/PCT/CRP until drain removal; IL-1β/TNFα/ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at meningitis detection; serum 25-OH-D on drain insertion day and day 14. Outcomes at days 30/90/180: mortality, GOSE, Barthel, Karnofsky, mRS. Statistics: normality testing; t-test or non-parametric equivalents; χ² with Yates' correction; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.
Endpoints DCI: new unexplained CT ischaemia or a new unexplained neurological deficit >1 h. Drain-associated infection: infectologist-adjudicated ventriculitis/meningitis. Vasospasm: TCCD-suggested or DSA-confirmed.
Expected impact An accessible CSF/serum biomarker panel may enable earlier risk stratification and treatment for vasospasm, DCI, and drain-associated infections, and inform future randomized trials of vitamin-D supplementation in SAH.
Read the detailed description
Brief Summary This single-centre prospective case-control study will evaluate whether a CSF/serum biomarker panel (IL-6, IL-1β, TNFα, PCT, CRP, adrenomedullin) can improve the early diagnosis and risk stratification of cerebral vasospasm, delayed cerebral ischaemia (DCI), and drain-associated ventriculitis/meningitis in adults treated for non-traumatic SAH with external CSF drainage. The study also explores associations with serum 25-hydroxy-vitamin D.
Detailed Description Background: Bedside TCCD is non-invasive but has limited accuracy for vasospasm; DSA is the gold standard but invasive and not easily repeatable. Early, reliable biomarkers could identify high-risk patients sooner. External CSF drainage is standard after SAH but carries a 5-22% risk of ventriculitis/meningitis.
Objectives: Assess diagnostic/predictive performance (including ROC analyses) of IL-6, IL-1β, TNFα, PCT, CRP and adrenomedullin (ADM) in CSF and serum for vasospasm, DCI and drain-associated infection; compare against routine parameters; evaluate combined-biomarker utility; explore associations with 25-OH-vitamin D.
Sampling/monitoring: Daily TCCD for 14 days (extend to day 21 if severe vasospasm); suspected vasospasm if MFV >120 cm/s, severe if >200 cm/s. CSF IL-6/PCT/CRP daily until drain removal; IL-1β, TNFα, ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at infection detection; serum 25-OH-vitamin D on drain-insertion day and day 14. Outcomes collected at days 30/90/180 (mortality, GOSE, Barthel, Karnofsky, mRS).
Study Type Observational (Prospective; Case-Control).
Observational Model / Time Perspective Case-Control; Prospective.
Estimated Enrollment
~100 participants.
Outcome Measures Primary Outcome Measures Vasospasm occurrence (binary): TCCD suggestive (MFV >120 cm/s; severe >200 cm/s) and/or DSA-confirmed; diagnostic/predictive performance of biomarkers (e.g., ROC AUC). Time Frame: first 14 days post-ictus (to day 21 if severe vasospasm).
Delayed cerebral ischaemia (DCI) (binary): new unexplained ischaemia on native cranial CT or new unexplained neurological deficit lasting >1 hour; biomarker performance vs DCI status. Time Frame: during acute hospital course (typically within first 14 days).
Drain-associated ventriculitis/meningitis (binary): infectologist-adjudicated diagnosis during drainage; biomarker performance vs infection status. Time Frame: through duration of external drainage.
Secondary Outcome Measures Functional outcomes: mortality; Extended Glasgow Outcome Scale; Barthel Index; Karnofsky; modified Rankin Scale at days 30/90/180 post-ictus.
Comparative accuracy: biomarkers vs routine CSF/blood parameters (e.g., CSF cell count/composition/lactate; albumin \& glucose ratios; serum CRP/PCT/IL-6).
Combined-biomarker utility: added value of multi-marker panels over single markers.
Vitamin D exploratory analysis: correlation of biomarkers with admission and day-14 serum 25-OH-vitamin D.
Biospecimen CSF and blood samples collected for biomarker measurements (lab values used for analysis).
Eligibility Criteria
Inclusion:
- Adults (≥18 years).
- Angiography-identifiable non-traumatic SAH (regardless of source).
- Requires lumbar or ventricular drain as part of treatment.
Exclusion:
- Traumatic SAH.
- Patient/legal representative does not consent.
- Meningitis within 6 months prior to ictus.
- Immunosuppressed state (disease or medications affecting WBC number/function).
Groups/Cohorts (for analyses)
- Vasospasm (+/-) (TCCD-suggested or DSA-confirmed vs. absent).
- DCI (+/-) (meets DCI definition vs. absent).
- Drain-associated ventriculitis/meningitis (+/-) (infectologist-adjudicated vs. excluded).
Statistical Plan Normality testing; t-test or non-parametric equivalents; χ² with Yates' correction where appropriate; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.
Location University of Debrecen, Clinical Centre - Department of Anaesthesiology and Intensive Care, Debrecen, Hungary (Neurosurgical Intensive Care Unit).
Contacts Principal Investigator: Prof. Dr. Csilla Molnár - University of Debrecen, Clinical Centre, Department of Anaesthesiology and Intensive Care. (Phone/Email per site policy.)
Keywords Subarachnoid haemorrhage; vasospasm; delayed cerebral ischaemia; ventriculitis; meningitis; IL-6; IL-1β; TNFα; procalcitonin; CRP; adrenomedullin; CSF biomarkers; TCCD; vitamin D.
- Conditions
- Subarachnoid Haemorrhagic Stroke
What is being measured
The primary outcome is the main question the study is designed to answer.
DCI
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2025
- Study start1 Aug 2025
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subarachnoid Haemorrhagic StrokeStudies 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tamas Vegh, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Tamas Vegh, MD, University of Debrecen
- Investigators
- Csilla Molnár, MD PhD Full Professor, Principal investigator, University of Debrecen, Faculty of Medicine, Department of Anaesthesiology and Intensive Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07129603
- Sponsor's protocol ID
- AITT 2024/3
- Other IDs
- NNGYK/14357-2/2025, DE RKEB/IKEB 6947-2024
- Status last verified
- Apr 2025
- First submitted
- 11 Aug 2025
- Last updated
- 19 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Role of Inflammatory Markers in the Early Detection of Cerebral Vasospasm, Delayed Cerebral Ischemia, and Meningitis Associated With External Cerebrospinal Fluid Drainage After Non-Traumatic Subarachnoid Hemorrhage - A Prospective Case-Control Study
- ClinicalTrials.gov ID
- NCT07129603
- Acronym / sponsor ID
- AITT 2024/3
- Conditions
- Subarachnoid Haemorrhagic Stroke
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Tamas Vegh, MDUniversity, hospital or other
- Study start
- 1 Aug 2025 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 19 Aug 2025 (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.
Background Non-traumatic subarachnoid haemorrhage (SAH) is frequently complicated by delayed cerebral ischaemia (DCI) and by ventriculitis/meningitis when external CSF drains are used; bedside TCCD has limited accuracy for vasospasm detection, creating a need for early biomarkers.
Objective To assess the predictive and diagnostic performance of IL-6, IL-1β, TNFα, procalcitonin (PCT), C-reactive protein (CRP) and adrenomedullin (ADM) measured in CSF and serum for vasospasm, DCI, and drain-associated ventriculitis/meningitis after SAH; to test whether combining biomarkers improves accuracy versus routine parameters; and to explore associations with admission and day-14 serum 25-hydroxy-vitamin D.
Methods Prospective case-control study at the University of Debrecen (planned n≈100; enrolment 01-Nov-2024-31-Dec-2029). Adults with angiography-verified SAH requiring lumbar/ventricular drainage are included; traumatic SAH, prior 6-month meningitis, and immunosuppression are excluded. TCCD is performed daily for 14 days; suspected vasospasm is defined by mean flow velocity >120 cm/s, severe by >200 cm/s, with monitoring extended to day 21 if severe. Sampling: daily CSF IL-6/PCT/CRP until drain removal; IL-1β/TNFα/ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at meningitis detection; serum 25-OH-D on drain insertion day and day 14. Outcomes at days 30/90/180: mortality, GOSE, Barthel, Karnofsky, mRS. Statistics: normality testing; t-test or non-parametric equivalents; χ² with Yates' correction; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.
Endpoints DCI: new unexplained CT ischaemia or a new unexplained neurological deficit >1 h. Drain-associated infection: infectologist-adjudicated ventriculitis/meningitis. Vasospasm: TCCD-suggested or DSA-confirmed.
Expected impact An accessible CSF/serum biomarker panel may enable earlier risk stratification and treatment for vasospasm, DCI, and drain-associated infections, and inform future randomized trials of vitamin-D supplementation in SAH.
Detailed description
Brief Summary This single-centre prospective case-control study will evaluate whether a CSF/serum biomarker panel (IL-6, IL-1β, TNFα, PCT, CRP, adrenomedullin) can improve the early diagnosis and risk stratification of cerebral vasospasm, delayed cerebral ischaemia (DCI), and drain-associated ventriculitis/meningitis in adults treated for non-traumatic SAH with external CSF drainage. The study also explores associations with serum 25-hydroxy-vitamin D.
Detailed Description Background: Bedside TCCD is non-invasive but has limited accuracy for vasospasm; DSA is the gold standard but invasive and not easily repeatable. Early, reliable biomarkers could identify high-risk patients sooner. External CSF drainage is standard after SAH but carries a 5-22% risk of ventriculitis/meningitis.
Objectives: Assess diagnostic/predictive performance (including ROC analyses) of IL-6, IL-1β, TNFα, PCT, CRP and adrenomedullin (ADM) in CSF and serum for vasospasm, DCI and drain-associated infection; compare against routine parameters; evaluate combined-biomarker utility; explore associations with 25-OH-vitamin D.
Sampling/monitoring: Daily TCCD for 14 days (extend to day 21 if severe vasospasm); suspected vasospasm if MFV >120 cm/s, severe if >200 cm/s. CSF IL-6/PCT/CRP daily until drain removal; IL-1β, TNFα, ADM at 0-2, 3-5, 6-8, 9-11, 12-14 days and at infection detection; serum 25-OH-vitamin D on drain-insertion day and day 14. Outcomes collected at days 30/90/180 (mortality, GOSE, Barthel, Karnofsky, mRS).
Study Type Observational (Prospective; Case-Control).
Observational Model / Time Perspective Case-Control; Prospective.
Estimated Enrollment
~100 participants.
Outcome Measures Primary Outcome Measures Vasospasm occurrence (binary): TCCD suggestive (MFV >120 cm/s; severe >200 cm/s) and/or DSA-confirmed; diagnostic/predictive performance of biomarkers (e.g., ROC AUC). Time Frame: first 14 days post-ictus (to day 21 if severe vasospasm).
Delayed cerebral ischaemia (DCI) (binary): new unexplained ischaemia on native cranial CT or new unexplained neurological deficit lasting >1 hour; biomarker performance vs DCI status. Time Frame: during acute hospital course (typically within first 14 days).
Drain-associated ventriculitis/meningitis (binary): infectologist-adjudicated diagnosis during drainage; biomarker performance vs infection status. Time Frame: through duration of external drainage.
Secondary Outcome Measures Functional outcomes: mortality; Extended Glasgow Outcome Scale; Barthel Index; Karnofsky; modified Rankin Scale at days 30/90/180 post-ictus.
Comparative accuracy: biomarkers vs routine CSF/blood parameters (e.g., CSF cell count/composition/lactate; albumin \& glucose ratios; serum CRP/PCT/IL-6).
Combined-biomarker utility: added value of multi-marker panels over single markers.
Vitamin D exploratory analysis: correlation of biomarkers with admission and day-14 serum 25-OH-vitamin D.
Biospecimen CSF and blood samples collected for biomarker measurements (lab values used for analysis).
Eligibility Criteria
Inclusion:
- Adults (≥18 years).
- Angiography-identifiable non-traumatic SAH (regardless of source).
- Requires lumbar or ventricular drain as part of treatment.
Exclusion:
- Traumatic SAH.
- Patient/legal representative does not consent.
- Meningitis within 6 months prior to ictus.
- Immunosuppressed state (disease or medications affecting WBC number/function).
Groups/Cohorts (for analyses)
- Vasospasm (+/-) (TCCD-suggested or DSA-confirmed vs. absent).
- DCI (+/-) (meets DCI definition vs. absent).
- Drain-associated ventriculitis/meningitis (+/-) (infectologist-adjudicated vs. excluded).
Statistical Plan Normality testing; t-test or non-parametric equivalents; χ² with Yates' correction where appropriate; Bonferroni for multiplicity; ROC analysis for diagnostic/predictive performance.
Location University of Debrecen, Clinical Centre - Department of Anaesthesiology and Intensive Care, Debrecen, Hungary (Neurosurgical Intensive Care Unit).
Contacts Principal Investigator: Prof. Dr. Csilla Molnár - University of Debrecen, Clinical Centre, Department of Anaesthesiology and Intensive Care. (Phone/Email per site policy.)
Keywords Subarachnoid haemorrhage; vasospasm; delayed cerebral ischaemia; ventriculitis; meningitis; IL-6; IL-1β; TNFα; procalcitonin; CRP; adrenomedullin; CSF biomarkers; TCCD; vitamin D.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults (≥18 years) admitted to the Neurosurgical Intensive Care Unit of the University of Debrecen Clinical Centre with non-traumatic subarachnoid haemorrhage (SAH) who, as part of standard care, require external CSF drainage (lumbar or ventricular). Patients are treated per local protocol and monitored with routine severity scales (modified Fisher, Hunt-Hess, WFNS, GCS, VASOGRADE, HAIR). Key exclusions are traumatic SAH, lack of consent, meningitis within the prior 6 months, and clinically relevant immunosuppression. Approximately 100 consecutive eligible patients will be enrolled during the acute hospitalization over the planned inclusion window. The cohort reflects the typical SAH case-mix (both sexes, many critically ill; SAH commonly affects middle-aged adults) and is designed to capture patients at risk for vasospasm, delayed cerebral ischaemia and drain-associated ventriculitis/meningitis under ICU conditions.
Key inclusion criteria (3 listed)
- Adults (≥18 years).
- Angiography-identifiable non-traumatic SAH (regardless of source).
- Requires lumbar or ventricular drain as part of treatment.
Key exclusion criteria (4 listed)
- Traumatic SAH.
- Patient/legal representative does not consent.
- Meningitis within 6 months prior to ictus.
- Immunosuppressed state (disease or medications affecting WBC number/function).
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
DCI
Time frame: 30 days
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 19 Aug 2025.
- Individual participant dataSharing planned: Undecided
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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.
Csilla Molnár, MD PhD Full Professor principal investigator
University of Debrecen, Faculty of Medicine, Department of Anaesthesiology and Intensive Care
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 Subarachnoid Haemorrhagic Stroke, run by Tamas Vegh, MD at 1 site in Hungary.
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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 19 Aug 2025. 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 Hungary. 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 Csilla Molnár, MD PhD Full Professor (+36302998097, csmolnar@med.unideb.hu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DCI (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Aug 2025.