Clinical trial NCT04998370: Cerebrospinal Fluid Hemoglobin to Monitor for Aneurysmal Subarachnoid Hemorrhage Related Secondary Brain Injury
Official title: Hemoglobin in the Cerebrospinal Fluid to Monitor for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage - a Prospective Multinational Validation Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Vasospasm
Delayed Cerebral Ischemia
Delayed Ischemic Neurological Deficit
Keywords: Cerebrospinal Fluid
Hemoglobins
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 409
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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 EVD, while secondary objectives consider patients with both, EVD and LD as well as patients without any drainage system.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI)
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Secondary outcomes:
measure: Angiographic vasospasms (aVSP)
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Delayed cerebral ischemia (DCI)
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Delayed ischemic neurologic deficits (DIND)
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Co-intervention 1: Nimodipine treatment
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Co-intervention 2: Spasmolysis
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Co-intervention 3: Intraventricular administration of rtPA (ICV-rtPA)
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Co-intervention 4: Triple-H-therapy
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Co-intervention 5: Decompression
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Complication 1: CSF infection
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Complication 2: Surgical site infection
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
measure: Chronic hydrocephalus
timeFrame: 12 weeks follow-up visit
measure: Functional status 1: Glasgow Outcome Scale Extended [1-8]
timeFrame: 12 weeks follow-up visit
measure: Functional status 2: modified Rankin Scale [0-6]
timeFrame: 12 weeks follow-up visit
Other outcomes:
measure: Cerebrospinal fluid hemoglobin
timeFrame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Locations:
city: Linz
country: Austria
facility: Johannes Kepler Universität Linz, Universitätsklinik für Neurochirurgie
city: Wien
country: Austria
facility: Medizinische Universität Wien, Klinik für Neurochirurgie
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum rechts der Isar TUM
state: Bayern
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Saint Gallen
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Hospital and University of Zurich, Department of Neurosurgery
name: Michael Hugelshofer, MD MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital and University of Zurich, Department of Neurosurgery
name: Kevin Akeret, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital and University of Zurich, Department of Internal Medicine
name: Dominik J Schaer, MD
role: STUDY_CHAIR
affiliation: University Hospital and University of Zurich, Department of Internal Medicine
name: Raphael M Buzzi, MD/PhD
role: STUDY_CHAIR
References:
citation: Akeret K, Buzzi RM, Saxenhofer M, Bieri K, Chiavi D, Thomson BR, Gruttner-Durmaz M, Schwendinger N, Humar R, Regli L, van Doormaal TPC, Held U, Keller E, Hugelshofer M, Schaer DJ; HeMoVal Research Group. The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury. BMC Neurol. 2022 Jul 18;22(1):267. doi: 10.1186/s12883-022-02789-w.