Cerebrospinal Fluid Hemoglobin to Monitor for Aneurysmal Subarachnoid Hemorrhage Related Secondary Brain Injury

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the association between hemoglobin levels in the cerebrospinal fluid (CSF-Hb) and the occurrence of secondary brain injury in patients after aneurysmal subarachnoid hemorrhage (SAH-SBI) during the first 14 days after bleeding.

Detailed Description
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This is an international multicentre observational study to validate cerebrospinal fluid hemoglobin (CSF-Hb) as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI). It is hypothesized that there is an association between the concentration of CSF-Hb and the occurrence of SAH-SBI during the first 14 days after the bleeding (post-SAH). The primary objective of this study is to evaluate the association between ventricular CSF-Hb and SAH-SBI during the first 14 days post-SAH. The secondary objectives are to investigate: the association between ventricular CSF-Hb and angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI) and delayed ischemic neurological deficits (DIND) during the first 14 days post-SAH, the accuracy of ventricular CSF-Hb to monitor for aVSP, DCI and DIND during the first 14 days post-SAH, the association between lumbar CSF-Hb and SAH-SBI, aVSP, DCI and DIND during the first 14 days post-SAH, the accuracy of lumbar CSF-Hb to monitor for aVSP, DCI and DIND during the first 14 days post-SAH, the association between baseline measures and CSF-Hb (ventricular and lumbar during the first 14 days post-SAH), the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and co-interventions/complications, the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and chronic hydrocephalus at 12 weeks follow-up, the association between CSF-Hb (ventricular and lumbar during the first 14 days post-SAH) and functional outcome at 12 weeks follow-up, exploratory CSF proteome/metabolome analyses to assess Hb toxicity, inflammation, neuronal, or vascular damage.

Official Title
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Hemoglobin in the Cerebrospinal Fluid to Monitor for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage - a Prospective Multinational Validation Study

Conditions
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Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Delayed Cerebral Ischemia, Delayed Ischemic Neurological Deficit

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years hospital admission due to an aneurysmal subarachnoid hemorrhage (diagnosis radiologically confirmed) Exclusion Criteria: non-aneurysmal subarachnoid hemorrhage (eg. trauma, perimesencephalic subarachnoid hemorrhage). participation in another study with CSF sampling or an interventional medical product within the 30 days preceding and during the present study. previous enrolment into the current study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study cohort<br>The study population consists of patients admitted to an academic tertiary care center due to an aneurysmal subarachnoid hemorrhage. The primary objective of the study focuses on patients included with external ventricular drain (EVD), while secondary objectives consider patients with both EVD and lumbar drain (LD) as well as patients without any drainage system. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI) | Composite outcome consisting of angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI), or delayed ischemic neurological deficits (DIND). | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiographic vasospasms (aVSP) | The definition of aVSP comprises a narrowing of cerebral arteries based on a digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA). In the absence of an appropriate imaging procedure on the respective day, this will be noted as no imaging performed. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Delayed cerebral ischemia (DCI) | DCI is defined as new ischemia or new infarction on CT/perfusion CT or MRI. In the absence of an appropriate imaging procedure on the respective day, this will be noted as no imaging performed. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Delayed ischemic neurologic deficits (DIND) | DIND is defined as a new focal neurological deficit or a decrease in Glasgow Coma Scale (GCS) of at least 2 points for at least 2 hours. In case the patient cannot be clinically assessed (e.g., sedation), this will be noted as non-assessable). | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Co-intervention 1: Nimodipine treatment | Whether the patient received preventive nimodipine treatment within the past 24 hours. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Co-intervention 2: Spasmolysis | Whether a rescue therapy with pharmacological spasmolysis or balloon angioplasty was performed within the past 24 hours. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Co-intervention 3: Intraventricular administration of rtPA (ICV-rtPA) | Whether rtPA was administered via the EVD to induce blood clot lysis within the past 24 hours. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Co-intervention 4: Triple-H-therapy | A triple-H-therapy or elements of it (hypertension, hypervolemia or hemodilution) was induced within the past 24 hours. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Co-intervention 5: Decompression | A surgical decompression (e.g. decompressive hemicraniectomy) was performed within the past 24 hours. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Complication 1: CSF infection | Differentiated between infection (Clinical symptoms and signs of CSF infection and positive CSF culture), colonization (2 positive CSF cultures without clinical symptoms and signs) and contamination (1 positive CSF culture with consecutive culture being negative). | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Complication 2: Surgical site infection | Evidence for a surgical site infection at the EVD/LD skin entrance site. | Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage | 
| Chronic hydrocephalus |  | 12 weeks follow-up visit | 
| Functional status 1: Glasgow Outcome Scale Extended [1-8] | Death Vegetative state (unresponsive and speechless) Lower severe disability (requires frequent help of someone to be around at home most of the time every day) Upper severe diasbility (can be left alone > 8h during the day, but unable to travel and/or go shopping without assistance) Lower moderate disability (unable to work or only in sheltered workshop) Upper moderate disability (reduced work capacity; resumes <50% of the pre-injury level of social and leisure activities) Lower good recovery (minor problems that affect daily life; resumes >50% of the pre-injury level of social and leisure activities) Upper good recovery (no current problems related to the brain injury that affect daily life) | 12 weeks follow-up visit | 
| Functional status 2: modified Rankin Scale [0-6] | 0 No symptoms No significant disability. Able to carry out all usual activities, despite some symptoms. Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. Moderate disability. Requires some helpt, but able to walk unassisted. Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. Severe disability. Requires constant nursing care and attention, bedridden, incontinent. Dead | 12 weeks follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebrospinal Fluid, Hemoglobins