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

Subarachnoid Hemorrhage, Aneurysmal Clinical Trial

— HeMoVal  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04998370
• Other study ID #: 2021-01023
• Status: Recruiting
• Start date: August 18, 2021
• Est. completion date: October 30, 2024

Study information

• Verified date: May 2024
• Source: University of Zurich
• Contact: Michael Hugelshofer, MD MSc
• Phone: 0041432531598
• Email: michael.hugelshofer[@]usz.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: October 30, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Ischemia
• Cerebral Infarction
• Delayed Cerebral Ischemia
• Delayed Ischemic Neurological Deficit
• Hemorrhage
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal
• Vasospasm

Locations

Country	Name	City	State
Austria	Johannes Kepler Universität Linz, Universitätsklinik für Neurochirurgie	Linz
Austria	Medizinische Universität Wien, Klinik für Neurochirurgie	Wien
Germany	Universitätsklinikum Mannheim	Mannheim	Baden-Württemberg
Germany	Klinikum rechts der Isar TUM	München	Bayern
Germany	Universitätsklinikum Tübingen	Tübingen
Switzerland	Kantonsspital Aarau	Aarau	Aargau
Switzerland	Kantonsspital St. Gallen	St. Gallen	Saint Gallen
Switzerland	University Hospital Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cerebrospinal fluid hemoglobin	CSF sampling: CSF sampling will be performed via EVD or LD, depending on the patient's access to the CSF space. The decision regarding the insertion of an EVD or LD is made independently of this study and according to the clinical standard of care. 2ml of CSF will be sampled on a daily basis at approximately the same time in the morning.; CSF centrifugation and storage: Immediately after sample collection, the CSF will be centrifuged at 1500 G for 15 minutes. The cell-free CSF supernatant will be stored at -80°C until analysis.; Spectrophotometric cerebrospinal fluid hemoglobin (CSF-Hb) measurements: Absorption spectra in the visual range between 350 and 650 nm of all CSF samples will be measured. Quantification of oxyhemoglobin in CSF (CSF-Hb) will be performed using spectral deconvolution.	Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Chronic hydrocephalus		12 weeks follow-up visit
Secondary	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
Secondary	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