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

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorTamas Vegh, MD

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Adults (≥18 years).

Angiography-identifiable non-traumatic SAH (regardless of source).

Requires lumbar or ventricular drain as part of treatment.

Disqualifiers

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 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.

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

No trial groups listed

Trial outcomes

Primary outcomes

1

DCI

Time frame
30 days

Secondary outcomes

Other outcomes

Sponsors and contacts

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Tamas Vegh, MD

Lead sponsor

University of Debrecen

Sponsor institution