Clinical trial NCT06119061: Telavancin Blood and Cerebrospinal Fluid Concentrations in Patients With Subarachnoid Hemorrhage
Official title: Telavancin Blood and Cerebrospinal Fluid Concentrations in Patients With Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Keywords: pharmacokinetics
augmented renal clearance
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Cumberland Pharmaceuticals
First posted: 2023-11-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The proposed study aims to evaluate the CNS penetration of telavancin in a critically ill population using cerebrospinal fluid (CSF) drawn from external ventricular drains (EVDs) in patients who have had spontaneous subarachnoid hemorrhage (SAH). Patients with SAH were chosen as the target population because they frequently require prolonged admission to the intensive care unit and drainage of CSF in order to prevent hydrocephalus. The estimated sample size is 20 subjects. This is a prospective cohort of patients with SAH. Patients will be included if they have a spontaneous SAH, aged 18-65 years old, Hunt-Hess score of 1-4 \& has an actively draining ventriculostomy.

Subjects will receive telavancin 10mg/kg (maximum 1000mg) every 24 hours for 3 consecutive doses. Serial serum and CSF samples will be obtained. An 8-hour urine collection will be completed on study day 2 in order to define the patient's measured creatinine clearance.

Detailed description: Telavancin exhibits potent and durable activity against target pathogens for bacterial meningitis and ventriculitis. There is a potential role for telavancin in treating Gram positive CNS pathogens, particularly in patients with resistant pathogens or in those who are intolerant to other commonly used antimicrobials. The proposed study aims to evaluate the CNS penetration of telavancin in a critically ill population using cerebrospinal fluid (CSF) drawn from external ventricular drains (EVDs) in patients who have had spontaneous subarachnoid hemorrhage (SAH). Patients with SAH were chosen as the target population because they frequently require prolonged admission to the intensive care unit and drainage of CSF in order to prevent hydrocephalus. The estimated sample size is 15 subjects.

Methods: This is a prospective cohort of patients with SAH. Patients will be included if they have a spontaneous SAH, aged 18-65 years old, Hunt-Hess score of 1-4 \& has an actively draining ventriculostomy. Patients will be excluded if they have a history of telavancin or similar agents, reduced renal function (estimated creatinine clearance \< 50ml/min) at the time of consent, severe anemia (hemoglobin \< 7gm/dl), vulnerable population (pregnant, prisoner).

Subjects will receive telavancin 10mg/kg (maximum 1000mg) every 24 hours for 3 consecutive doses. Baseline serum and CSF samples will be drawn before the initial dose of telavancin. Serial serum and CSF samples will be obtained after the first and third doses (1, 3, 6, 23 hours after infusion). A terminal concentration will also be obtained approximately 48 hours after the last dose. An 8-hour urine collection will be completed on study day 2 in order to define the patient's measured creatinine clearance.

Major Goals Goal 1. Determine the CNS penetration of telavancin in critically ill patients with SAH. Serial CSF and serum samples will be obtained from SAH patients with EVDs before and after scheduled telavancin doses in order to determine the degree of CNS penetration of telavancin.

Goal 2. Describe the pharmacokinetics of telavancin in critically ill patients with SAH. Patients with SAH frequently exhibit augmented renal clearance.(5) This increase in renal clearance has been demonstrated to affect the pharmacokinetics of numerous renally-eliminated medications. Volume of distribution may also be affected for many medications (such as telavancin) due to the frequent aggressive measures needed to maintain euvolemia or hypervolemia in some instances (due to SAH-induced vasospasm) and changes in serum albumin concentrations.

Eligibility criteria: Inclusion Criteria:

* Spontaneous subarachnoid hemorrhage
* Hunt-Hess score of 1-4
* Actively draining ventriculostomy

Exclusion Criteria:

* history of hypersensitivity to telavancin or similar agents
* reduced renal function (estimated creatinine clearance \< 50/ml) at the time of consent
* severe anemia (hemoglobin \< 7gm/dl)
* vulnerable population (pregnant, prisoner)

Primary outcomes:
measure: Determine the CNS penetration of telavancin in critically ill patients with SAH
timeFrame: 3 days
Secondary outcomes:
measure: Describe the pharmacokinetics of telavancin in critically ill patients with SAH
timeFrame: 5 days
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Aaron M Cook, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Stucki A, Gerber P, Acosta F, Cottagnoud M, Cottagnoud P. Efficacy of telavancin against penicillin-resistant pneumococci and Staphylococcus aureus in a rabbit meningitis model and determination of kinetic parameters. Antimicrob Agents Chemother. 2006 Feb;50(2):770-3. doi: 10.1128/AAC.50.2.770-773.2006.
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