Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration

NCT ID: NCT04649398

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-25
• Study Completion Date: 2025-12-31

Brief 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 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

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Delayed Cerebral Ischemia; Vasospasm, Cerebral

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

oral nimodipine

60mg of nimodipine is orally administered every 4 h,

Nimodipine

Intervention Type: DRUG

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.

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

Nimodipine

Intervention Type: DRUG

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.

intra-arterial nimodipine

during endovascular procedure 2mg of nimodipine is infused via a microcatheter into the internal carotid artery for 20 minutes

Nimodipine

Intervention Type: DRUG

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.

Interventions

Nimodipine

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Vienna

OTHER

Sponsor Role: collaborator

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Arthur Hosmann

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Arthur Hosmann, MD PhD

Role: CONTACT

arthur.hosmann@meduniwien.ac.at

+43/1/40400 ext. 25650

Facility Contacts

Arthur Hosmann, MD PhD

Role: primary

arthur.hosmann@meduniwien.ac.at

+43/1/40400 ext. 25650

Other Identifiers

Brain_MD_Nimodipine

Identifier Type: -

Identifier Source: org_study_id