Subarachnoid Hemorrhage, AneurysmalHeMoValNCT04998370
Cerebrospinal Fluid Hemoglobin to Monitor for Aneurysmal Subarachnoid Hemorrhage Related Secondary Brain Injury
An observational study of Subarachnoid Hemorrhage, Aneurysmal and Vasospasm, run by University of Zurich at 8 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Delayed Cerebral Ischemia
- How many people
- 366 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 18 Aug 2021to 1 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- age ≥ 18 years
- hospital admission due to an aneurysmal subarachnoid hemorrhage (diagnosis radiologically confirmed)
Who cannot join
- 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
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Germany3 sites
Universitätsklinikum Mannheim
Mannheim, Baden-Wurttemberg, 68167
Klinikum rechts der Isar TUM
München, Bavaria, 81675
Universitätsklinikum Tübingen
Tübingen, Tübingen, 72076
Switzerland3 sites
Kantonsspital Aarau
Aarau, Canton of Aargau, CH-5001
Kantonsspital St. Gallen
Sankt Gallen, Canton of St. Gallen, CH-9007
University Hospital Zurich
Zurich, Canton of Zurich, 8091
Austria2 sites
Johannes Kepler Universität Linz, Universitätsklinik für Neurochirurgie
Linz, 4040
Medizinische Universität Wien, Klinik für Neurochirurgie
Vienna, 1090
About this study
Official title: Hemoglobin in the Cerebrospinal Fluid to Monitor for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage - a Prospective Multinational Validation Study
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.
Read the 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.
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Delayed Cerebral Ischemia, Delayed Ischemic Neurological Deficit
- Keywords
- Cerebrospinal Fluid, Hemoglobins
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Study cohort | 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 being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Chronic hydrocephalus
Measured: 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)
Measured: 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
Measured: 12 weeks follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start18 Aug 2021
- Primary completion30 Sep 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 366 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Hugelshofer, University of Zurich
- Investigators
- Michael Hugelshofer, MD MSc, Principal investigator, University Hospital and University of Zurich, Department of NeurosurgeryKevin Akeret, MD/PhD, Principal investigator, University Hospital and University of Zurich, Department of NeurosurgeryDominik J Schaer, MD, Study chair, University Hospital and University of Zurich, Department of Internal MedicineRaphael M Buzzi, MD/PhD, Study chair, University Hospital and University of Zurich, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04998370
- Sponsor's protocol ID
- 2021-01023
- Acronym
- HeMoVal
- Status last verified
- Dec 2025
- First submitted
- 19 Jul 2021
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35850705
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemoglobin in the Cerebrospinal Fluid to Monitor for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage - a Prospective Multinational Validation Study
- ClinicalTrials.gov ID
- NCT04998370
- Acronym / sponsor ID
- HeMoVal / 2021-01023
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Vasospasm, Delayed Cerebral Ischemia, Delayed Ischemic Neurological Deficit
- Keywords
- Cerebrospinal Fluid, Hemoglobins
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 366 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 18 Aug 2021 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study cohort | – | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- age ≥ 18 years
- hospital admission due to an aneurysmal subarachnoid hemorrhage (diagnosis radiologically confirmed)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI)
Time frame: 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).
13 secondary outcomes
Angiographic vasospasms (aVSP)
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Delayed cerebral ischemia (DCI)
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Delayed ischemic neurologic deficits (DIND)
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Co-intervention 1: Nimodipine treatment
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Co-intervention 2: Spasmolysis
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Co-intervention 3: Intraventricular administration of rtPA (ICV-rtPA)
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Co-intervention 4: Triple-H-therapy
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Co-intervention 5: Decompression
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Complication 1: CSF infection
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Complication 2: Surgical site infection
Time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage
Chronic hydrocephalus
Time frame: 12 weeks follow-up visit
Functional status 1: Glasgow Outcome Scale Extended [1-8]
Time frame: 12 weeks follow-up visit
Functional status 2: modified Rankin Scale [0-6]
Time frame: 12 weeks follow-up visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Derived from this study: PubMed 35850705Akeret 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Hugelshofer, MD MSc principal investigator
University Hospital and University of Zurich, Department of Neurosurgery
Kevin Akeret, MD/PhD principal investigator
University Hospital and University of Zurich, Department of Neurosurgery
Dominik J Schaer, MD study chair
University Hospital and University of Zurich, Department of Internal Medicine
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subarachnoid Hemorrhage, Aneurysmal and Vasospasm, run by University of Zurich at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, Switzerland, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aneurysmal subarachnoid hemorrhage related secondary brain injury (SAH-SBI) (time frame: Day 1 to day 14 after the aneurysmal subarachnoid hemorrhage). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04998370, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.