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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04649398
Other study ID # Brain_MD_Nimodipine
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date November 25, 2020
Est. completion date December 31, 2025

Study information

Verified date October 2023
Source Medical University of Vienna
Contact Arthur Hosmann, MD PhD
Phone +43/1/40400
Email arthur.hosmann@meduniwien.ac.at
Is FDA regulated No
Health authority
Study type Observational

Clinical 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 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


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date December 31, 2025
Est. primary completion date July 31, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 95 Years
Eligibility 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

Study Design


Intervention

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.

Locations

Country Name City State
Austria Medical University of Vienna Vienna

Sponsors (3)

Lead Sponsor Collaborator
Medical University of Vienna Austrian Science Fund (FWF), University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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) during the intervention
Primary cerebral ethanol concentrations Area under the concentration-time curve and maximum concentrations in brain tissue, CSF and blood after intravenous administration during the intervention
Secondary cerebral lactate/pyruvate ratio (LPR) determined by cerebral microdialysis during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
Secondary brain tissue oxygen tension (pbtO2) determined by cerebral parenchymal probes during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
Secondary cardiac output measured by Pulse Contour Cardiac Output (PiCCO) monitoring during the intervention
Secondary fluid responsiveness measured by Pulse Contour Cardiac Output (PiCCO) monitoring during the intervention
Secondary extravascular lung water index measured by Pulse Contour Cardiac Output (PiCCO) monitoring during the intervention
Secondary systemic vascular resistance index measured by Pulse Contour Cardiac Output (PiCCO) monitoring during the intervention
Secondary transcranial doppler flow velocities measured in the middle cerebral artery ipsilateral to the microdialysis probe during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
Secondary angiographic vasospasm mild: vessel diameter from 60-99%, moderate: vessel diameter from 30-59%, severe: vessel diameter <30% of the physiological lumen immediately after the intervention
Secondary cerebral perfusion pressure measured continuously via intra-arterial and intracranial probes during the intervention for oral and intravenous administered nimodipine, 12 hours after the intervention for intra-arterial nimodipine administration
Secondary incidence of delayed ischemic strokes ischemic strokes on CT scans 3-21 days following subarachnoid haemorrhage
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