Ignite Creation Date:
2025-12-24 @ 7:11 PM
Ignite Modification Date:
2025-12-29 @ 3:31 PM
Study NCT ID:
NCT07129603
Status:
RECRUITING
Last Update Posted:
2025-08-19
First Post:
2025-08-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief 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
Sponsor:
Tamas Vegh, MD
Organization:
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2025-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: