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

Last updated: October 18, 2023
Sponsor: Medical University of Vienna
Overall Status: Active - Recruiting

Phase

N/A

Condition

Hemorrhage

Cerebral Ischemia

Stroke

Treatment

Nimodipine

Clinical Study ID

NCT04649398
Brain_MD_Nimodipine
  • Ages 18-95
  • All Genders

Study 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

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • patient age > 18 years
  • aneurysmal subarachnoid hemorrhage
  • sedated and mechanically ventilated
  • application of brain microdialysis as standard care (due to the severity ofsubarachnoid haemorrhage or secondary deterioration)
  • oral, intra-venous or intra-arterial administration of nimodipine due to clinicalindication

Exclusion

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 thepatient, at the discretion of the investigator

Study Design

Total Participants: 30
Treatment Group(s): 1
Primary Treatment: Nimodipine
Phase:
Study Start date:
November 25, 2020
Estimated Completion Date:
December 31, 2025

Connect with a study center

  • Medical University of Vienna

    Vienna, 1090
    Austria

    Active - Recruiting

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