Cerebrospinal Fluid Hemoglobin to Monitor for Aneurysmal Subarachnoid Hemorrhage Related Secondary Brain Injury
- Conditions
- Subarachnoid Hemorrhage, AneurysmalDelayed Ischemic Neurological DeficitVasospasmDelayed Cerebral Ischemia
- Registration Number
- NCT04998370
- Lead Sponsor
- University of Zurich
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 409
- age ≥ 18 years
- hospital admission due to an aneurysmal subarachnoid hemorrhage (diagnosis radiologically confirmed)
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI) Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage Composite outcome consisting of angiographic vasospasms (aVSP), delayed cerebral ischemia (DCI), or delayed ischemic neurological deficits (DIND).
- Secondary Outcome Measures
Name Time Method Co-intervention 5: Decompression Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage A surgical decompression (e.g. decompressive hemicraniectomy) was performed within the past 24 hours.
Chronic hydrocephalus 12 weeks follow-up visit Angiographic vasospasms (aVSP) Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage 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.
Delayed ischemic neurologic deficits (DIND) Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage 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).
Co-intervention 4: Triple-H-therapy Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage A triple-H-therapy or elements of it (hypertension, hypervolemia or hemodilution) was induced within the past 24 hours.
Complication 2: Surgical site infection Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage Evidence for a surgical site infection at the EVD/LD skin entrance site.
Delayed cerebral ischemia (DCI) Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage 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.
Co-intervention 3: Intraventricular administration of rtPA (ICV-rtPA) Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage Whether rtPA was administered via the EVD to induce blood clot lysis within the past 24 hours.
Co-intervention 1: Nimodipine treatment Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage Whether the patient received preventive nimodipine treatment within the past 24 hours.
Co-intervention 2: Spasmolysis Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage Whether a rescue therapy with pharmacological spasmolysis or balloon angioplasty was performed within the past 24 hours.
Complication 1: CSF infection Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage 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).
Functional status 1: Glasgow Outcome Scale Extended [1-8] 12 weeks follow-up visit 1. Death
2. Vegetative state (unresponsive and speechless)
3. Lower severe disability (requires frequent help of someone to be around at home most of the time every day)
4. Upper severe diasbility (can be left alone \> 8h during the day, but unable to travel and/or go shopping without assistance)
5. Lower moderate disability (unable to work or only in sheltered workshop)
6. Upper moderate disability (reduced work capacity; resumes \<50% of the pre-injury level of social and leisure activities)
7. Lower good recovery (minor problems that affect daily life; resumes \>50% of the pre-injury level of social and leisure activities)
8. Upper good recovery (no current problems related to the brain injury that affect daily life)Functional status 2: modified Rankin Scale [0-6] 12 weeks follow-up visit 0 No symptoms
1. No significant disability. Able to carry out all usual activities, despite some symptoms.
2. Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3. Moderate disability. Requires some helpt, but able to walk unassisted.
4. Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5. Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6. Dead
Trial Locations
- Locations (8)
University Hospital Zurich
🇨🇭Zurich, Switzerland
Universitätsklinikum Mannheim
🇩🇪Mannheim, Baden-Württemberg, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Johannes Kepler Universität Linz, Universitätsklinik für Neurochirurgie
🇦🇹Linz, Austria
Medizinische Universität Wien, Klinik für Neurochirurgie
🇦🇹Wien, Austria
Klinikum rechts der Isar TUM
🇩🇪München, Bayern, Germany
Kantonsspital St. Gallen
🇨🇭St. Gallen, Saint Gallen, Switzerland
Kantonsspital Aarau
🇨🇭Aarau, Aargau, Switzerland