NCT04649398

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

Determination of Cerebral Nimodipine Concentrations Following Oral, Intra-venous and Intra-arterial Administration - a Descriptive Pharmacokinetic/Pharmacodynamics Study

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 30 (estimated)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 95 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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.

Timeline

• Start date: 2020-11-25
• Primary completion: 2024-07-31
• Completion: 2025-12-31
• First posted: 2020-12-02
• Last updated: 2023-10-19

Locations

1 site across 1 country: Austria

Regulatory

• FDA-regulated drug study