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Telavancin Blood and Cerebrospinal Fluid Concentrations in Patients With Subarachnoid Hemorrhage

Phase 4
Recruiting
Conditions
Subarachnoid Hemorrhage, Aneurysmal
Interventions
Registration Number
NCT06119061
Lead Sponsor
Aaron Cook
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
20
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TelavancinTelavancin InjectionSubjects receiving telavancin for pharmacokinetic sampling
Primary Outcome Measures
NameTimeMethod
Determine the CNS penetration of telavancin in critically ill patients with SAH3 days

Telavancin concentrations in CSF drawn from external ventricular drains will be compared to samples from the serum to determine the degree to which telavancin is present in the CNS

Secondary Outcome Measures
NameTimeMethod
Describe the pharmacokinetics of telavancin in critically ill patients with SAH5 days

Analyze serial serum concentrations of telavancin to determine the population's clearance, half-life, \& volume of distribution

Trial Locations

Locations (1)

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

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