Subarachnoid Hemorrhage, AneurysmalNCT04649398
Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration
An observational study of Subarachnoid Hemorrhage, Aneurysmal and Delayed Cerebral Ischemia, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Nimodipine reduces the risk of poor outcome and delayed cerebral ischemia in patients suffering aneurysmal subarachnoid haemorrhage (SAH), but its mode of action is unknown. Its beneficial effect is assumed to be due its neuroprotective effects by reducing intracellular calcium and thereby cellular apoptosis, but… Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal, Delayed Cerebral Ischemia, Vasospasm, Cerebral
- What is being tested?
- Nimodipine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 30 participants
- Where
- 1 siteAustria
- Study dates
- 25 Nov 2020to 31 Dec 2025
- 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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients requiring intensive care and bedside cerebral microdialysis for cerebral neurochemical monitoring as standard care with a clinical indication for concomitant treatment with either oral, intra-venous or intra-arterial nimodipin
Who may be able to join
- patient age > 18 years
- aneurysmal subarachnoid hemorrhage
- sedated and mechanically ventilated
- application of brain microdialysis as standard care (due to the severity of subarachnoid haemorrhage or secondary deterioration)
- oral, intra-venous or intra-arterial administration of nimodipine due to clinical indication
Who cannot join
- contraindication for nimodipine
- no need of intensive care and bedside cerebral microdialysis as standard care
- any disease considered relevant for proper performance of the study or risks to the patient, at the discretion of the investigator
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, 1090
Arthur Hosmann, MD PhD, +43/1/40400 ext. 25650, arthur.hosmann@meduniwien.ac.at
About this study
Official title: Determination of Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration - a Descriptive Pharmacokinetic/Pharmacodynamics Study
Nimodipine reduces the risk of poor outcome and delayed cerebral ischemia in patients suffering aneurysmal subarachnoid haemorrhage (SAH), but its mode of action is unknown. Its beneficial effect is assumed to be due its neuroprotective effects by reducing intracellular calcium and thereby cellular apoptosis, but higher concentrations might induce marked systemic hypotension, thereby inducing cerebral ischemia. Since several dosing regimes and routes of administration with inconclusive superiority exist and since the target site concentration of nimodipine - the unbound drug concentrations beyond the blood-brain barrier - is still not known, it is reasonable to measure nimodipine concentrations within the blood, cerebrospinal fluid (CSF) and interstitial brain tissue following oral, intra-venous and intra-arterial administration and correlate intra-arterial nimodipine administration to measures of cerebral metabolism and oxygenation.
Therefore, the investigators propose to investigate in 30 patients suffering severe aneurysmal SAH and requiring cerebral microdialysis for cerebral neurochemical monitoring:
- the ability of nimodipine to penetrate into the brain of neurointensive care patients by comparing exposure in brain, CSF and plasma, dependent on the route of administration (i.e. oral, intra-venous, and intra-arterial) and dosing intra-venously (0.5 - 2mg/h)
- the impact of orally, intra-venously, and intra-arterially delivered nimodipine on cerebral metabolism, i.e. lactate/pyruvate ratio, pbtO2 and transcranial doppler flow velocities
- the effect of oral and intra-venous nimodipine on systemic hemodynamic and cardiac parameters, using continuous Pulse Contour Cardiac Output (PiCCO) monitoring
- the penetration properties of ethanol - as an excipient of nimodipine infusion - into the brain by comparing exposure in brain, CSF and plasma and quantifying the neuronal exposure to alcohol dependent on blood levels
- Being tested
- Nimodipine
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NimodipineDrug
If application of nimodipine is clinically indicated patients will be enrolled in the study protocol according to the inclusion and exclusion criteria. The clinically appropriate route of administration will be administered according to the recommended regimen of the study drug; i.e. within the first 10-14 days intra-venous infusion and thereafter oral administration. Intra-arterial infusion will be performed due to severe cerebral vasospasm with impending stroke.
| Study group | Role | What they receive |
|---|---|---|
| oral nimodipine | 60mg of nimodipine is orally administered every 4 h, Receives: Drug: Nimodipine | |
| intra-venous nimodipine | nimodipine is continuously administered intra-venously, starting with 0.5 mg/h on day 1 and increased every day for 0.5 mg/h to a maximum dose of 2.0mg/h on day 4 Receives: Drug: Nimodipine | |
| intra-arterial nimodipine | during endovascular procedure 2mg of nimodipine is infused via a microcatheter into the internal carotid artery for 20 minutes Receives: Drug: Nimodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
cerebral nimodipine concentrations
Area under the concentration-time curve in brain, cerebrospinal fluid and serum, dependent on the route of administration (i.e. oral, intra-venous, and intra-arterial)
Measured: during the intervention
cerebral ethanol concentrations
Area under the concentration-time curve and maximum concentrations in brain tissue, CSF and blood after intravenous administration
Measured: during the intervention
Secondary outcomes (10)
cerebral lactate/pyruvate ratio (LPR)
determined by cerebral microdialysis
Measured: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
brain tissue oxygen tension (pbtO2)
determined by cerebral parenchymal probes
Measured: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
cardiac output
measured by Pulse Contour Cardiac Output (PiCCO) monitoring
Measured: during the intervention
fluid responsiveness
measured by Pulse Contour Cardiac Output (PiCCO) monitoring
Measured: during the intervention
extravascular lung water index
measured by Pulse Contour Cardiac Output (PiCCO) monitoring
Measured: during the intervention
systemic vascular resistance index
measured by Pulse Contour Cardiac Output (PiCCO) monitoring
Measured: during the intervention
transcranial doppler flow velocities
measured in the middle cerebral artery ipsilateral to the microdialysis probe
Measured: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
angiographic vasospasm
mild: vessel diameter from 60-99%, moderate: vessel diameter from 30-59%, severe: vessel diameter <30% of the physiological lumen
Measured: immediately after the intervention
cerebral perfusion pressure
measured continuously via intra-arterial and intracranial probes
Measured: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
incidence of delayed ischemic strokes
ischemic strokes on CT scans
Measured: 3-21 days following subarachnoid haemorrhage
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2020
- Study start25 Nov 2020
- Primary completion31 Jul 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
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 Medical University of ViennaThe 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- University of Vienna, Austrian Science Fund (FWF)
- Responsible party
- Principal investigator, Arthur Hosmann, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04649398
- Sponsor's protocol ID
- Brain_MD_Nimodipine
- Status last verified
- Oct 2023
- First submitted
- 16 Nov 2020
- Last updated
- 19 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Moser MM, Rossler K, Hirschmann D, Gramss L, Tahir A, Plochl W, Herta J, Reinprecht A, Zeitlinger M, Hosmann A. Cerebral Ischemia Protection After Aneurysmal Subarachnoid Hemorrhage: CSF Nimodipine Levels After Intravenous Versus Oral Nimodipine Administration. Clin Pharmacol Ther. 2025 Feb;117(2):589-597. doi: 10.1002/cpt.3499. Epub 2024 Nov 19.
PubMed 39560199
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration - a Descriptive Pharmacokinetic/Pharmacodynamics Study
- ClinicalTrials.gov ID
- NCT04649398
- Acronym / sponsor ID
- Brain_MD_Nimodipine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- University of Vienna, Austrian Science Fund (FWF)
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 2 Dec 2020 (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.
Nimodipine reduces the risk of poor outcome and delayed cerebral ischemia in patients suffering aneurysmal subarachnoid haemorrhage (SAH), but its mode of action is unknown. Its beneficial effect is assumed to be due its neuroprotective effects by reducing intracellular calcium and thereby cellular apoptosis, but higher concentrations might induce marked systemic hypotension, thereby inducing cerebral ischemia. Since several dosing regimes and routes of administration with inconclusive superiority exist and since the target site concentration of nimodipine - the unbound drug concentrations beyond the blood-brain barrier - is still not known, it is reasonable to measure nimodipine concentrations within the blood, cerebrospinal fluid (CSF) and interstitial brain tissue following oral, intra-venous and intra-arterial administration and correlate intra-arterial nimodipine administration to measures of cerebral metabolism and oxygenation.
Therefore, the investigators propose to investigate in 30 patients suffering severe aneurysmal SAH and requiring cerebral microdialysis for cerebral neurochemical monitoring:
- the ability of nimodipine to penetrate into the brain of neurointensive care patients by comparing exposure in brain, CSF and plasma, dependent on the route of administration (i.e. oral, intra-venous, and intra-arterial) and dosing intra-venously (0.5 - 2mg/h)
- the impact of orally, intra-venously, and intra-arterially delivered nimodipine on cerebral metabolism, i.e. lactate/pyruvate ratio, pbtO2 and transcranial doppler flow velocities
- the effect of oral and intra-venous nimodipine on systemic hemodynamic and cardiac parameters, using continuous Pulse Contour Cardiac Output (PiCCO) monitoring
- the penetration properties of ethanol - as an excipient of nimodipine infusion - into the brain by comparing exposure in brain, CSF and plasma and quantifying the neuronal exposure to alcohol dependent on blood levels
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| oral nimodipine | – | Drug: Nimodipine60mg of nimodipine is orally administered every 4 h, |
| intra-venous nimodipine | – | Drug: Nimodipinenimodipine is continuously administered intra-venously, starting with 0.5 mg/h on day 1 and increased every day for 0.5 mg/h to a maximum dose of 2.0mg/h on day 4 |
| intra-arterial nimodipine | – | Drug: Nimodipineduring endovascular procedure 2mg of nimodipine is infused via a microcatheter into the internal carotid artery for 20 minutes |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients requiring intensive care and bedside cerebral microdialysis for cerebral neurochemical monitoring as standard care with a clinical indication for concomitant treatment with either oral, intra-venous or intra-arterial nimodipin
Key inclusion criteria (5 listed)
- patient age > 18 years
- aneurysmal subarachnoid hemorrhage
- sedated and mechanically ventilated
- application of brain microdialysis as standard care (due to the severity of subarachnoid haemorrhage or secondary deterioration)
- oral, intra-venous or intra-arterial administration of nimodipine due to clinical indication
Key exclusion criteria (3 listed)
- contraindication for nimodipine
- no need of intensive care and bedside cerebral microdialysis as standard care
- any disease considered relevant for proper performance of the study or risks to the patient, at the discretion of the investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NimodipineIf application of nimodipine is clinically indicated patients will be enrolled in the study protocol according to the inclusion and exclusion criteria. The clinically appropriate route of administration will be administered according to the recommended regimen of the study drug; i.e. within the first 10-14 days intra-venous infusion and thereafter oral administration. Intra-arterial infusion will be performed due to severe cerebral vasospasm with impending stroke. | Drug | intra-arterial nimodipine, intra-venous nimodipine, oral nimodipine |
Primary outcome
cerebral nimodipine concentrations
Time frame: during the intervention
Area under the concentration-time curve in brain, cerebrospinal fluid and serum, dependent on the route of administration (i.e. oral, intra-venous, and intra-arterial)
cerebral ethanol concentrations
Time frame: during the intervention
Area under the concentration-time curve and maximum concentrations in brain tissue, CSF and blood after intravenous administration
10 secondary outcomes
cerebral lactate/pyruvate ratio (LPR)
Time frame: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
brain tissue oxygen tension (pbtO2)
Time frame: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
cardiac output
Time frame: during the intervention
fluid responsiveness
Time frame: during the intervention
extravascular lung water index
Time frame: during the intervention
systemic vascular resistance index
Time frame: during the intervention
transcranial doppler flow velocities
Time frame: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
angiographic vasospasm
Time frame: immediately after the intervention
cerebral perfusion pressure
Time frame: during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
incidence of delayed ischemic strokes
Time frame: 3-21 days following subarachnoid haemorrhage
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2023.
- Derived from this study: PubMed 39560199Moser MM, Rossler K, Hirschmann D, Gramss L, Tahir A, Plochl W, Herta J, Reinprecht A, Zeitlinger M, Hosmann A. Cerebral Ischemia Protection After Aneurysmal Subarachnoid Hemorrhage: CSF Nimodipine Levels After Intravenous Versus Oral Nimodipine Administration. Clin Pharmacol Ther. 2025 Feb;117(2):589-597. doi: 10.1002/cpt.3499. Epub 2024 Nov 19.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subarachnoid Hemorrhage, Aneurysmal and Delayed Cerebral Ischemia, run by Medical University of Vienna at 1 site in Austria.
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 5 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: status not confirmed, as of the sponsor's last update on 19 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arthur Hosmann, MD PhD (+43/1/40400 ext. 25650, arthur.hosmann@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cerebral nimodipine concentrations (time frame: during the intervention). The study lists 2 primary outcomes in all. 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 NCT04649398, 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 19 Oct 2023.