Effect of Dialysis on the Pharmacokinetics of Telavancin in Patients With Chronic Kidney Disease Stage 5

Study Overview
=================
Brief Summary
-----------------
Chronic Kidney Disease Stage 5 (CKD5) patients receiving maintenance hemodialysis are at an increased risk for developing bloodstream infections. Vancomycin is traditionally used as first-line therapy for treating these infections, but the emergence of less-susceptible bacterial strains necessitates the consideration of alternative antibiotic therapy. Telavancin is a new antibiotic that has broad-spectrum antimicrobial activity against gram-positive bacteria, including vancomycin-intermediate staphylococcus aureus. While dosing recommendations for telavancin are available for patients with normal kidney function, there are no published recommendations for CKD5 patients receiving hemodialysis. A pharmacokinetic study is needed to characterize the pharmacokinetic parameters of telavancin in these patients to determine the extent of drug removal by hemodialysis and to establish dosing recommendations for CKD5 patients on maintenance hemodialysis.

Official Title
-----------------
Effect of Dialysis on the Pharmacokinetics of Telavancin in Patients With Chronic Kidney Disease Stage 5

Conditions
-----------------
End-Stage Renal Disease, Stage 5 Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: Telavancin
* Procedure: Pharmacokinetic Blood Sampling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years of age Within 50 - 150 % of ideal body weight and greater than 40 kg CKD5 receiving maintenance hemodialysis for ≥ 3 months Creatinine Clearance estimate < 10 mL/min Not received telavancin within the past month No concurrent illness or evidence of infection Able to give informed consent Exclusion Criteria: Pre-study Hemoglobin < 9.0 g/dL Plasma Albumin < 2.5 g/dL Pregnancy Breastfeeding QTc interval > 470 msec on EKG obtained within the last 6 months Receiving concomitant QT prolonging agents Receiving warfarin or low molecular weight heparin products Known allergy to telavancin or vancomycin Unstable blood pressure control Need for routine large fluid removal during dialysis (> 4 liters) Diagnosis of liver disease with a Child Pugh score of C or higher Dialysis isolation requirements due to Hepatitis B Participating concurrently in another investigational drug study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Telavancin Before Hemodialysis<br>Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin before their normally scheduled hemodialysis session. | Drug: Telavancin<br>* A single 5 mg/kg dose of telavancin is administered intravenously (IV).<br>* Other names: Vibativ;Procedure: Pharmacokinetic Blood Sampling<br>* Blood samples are collected to assess telavancin plasma concentrations.<br>* Other names: PK Sampling;|
| Other: Telavancin After Hemodialysis<br>Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin immediately after their normally scheduled hemodialysis session. | Drug: Telavancin<br>* A single 5 mg/kg dose of telavancin is administered intravenously (IV).<br>* Other names: Vibativ;Procedure: Pharmacokinetic Blood Sampling<br>* Blood samples are collected to assess telavancin plasma concentrations.<br>* Other names: PK Sampling;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Telavancin | Peak concentration of telavancin | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 
| Vss of Telavancin | Volume of distribution of telavancin at steady state | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 
| CLobs of Telavancin | Observed clearance of telavancin | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 
| t1/2 of Telavancin | Half-life of telavancin | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24 of Telavancin | Area under the telavancin concentration-time curve 0-24 hours from start of infusion | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 
| AUC24-48 of Telavancin | Area under the telavancin concentration-time curve 24-48 hours from start of infusion | At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
telavancin, end-stage renal disease, ESRD, pharmacokinetics, hemodialysis, chronic kidney disease, CKD, dialysis, Vibativ