Clinical trial NCT02392208: Effect of Dialysis on the Pharmacokinetics of Telavancin in Patients With Chronic Kidney Disease Stage 5
Official title: Effect of Dialysis on the Pharmacokinetics of Telavancin in Patients With Chronic Kidney Disease Stage 5
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-Stage Renal Disease
Stage 5 Chronic Kidney Disease
Keywords: telavancin
end-stage renal disease
ESRD
pharmacokinetics
hemodialysis
chronic kidney disease
CKD
dialysis
Vibativ
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Theravance Biopharma
First posted: 2015-03-18
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Cmax of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
measure: Vss of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
measure: CLobs of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
measure: t1/2 of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
Secondary outcomes:
measure: AUC0-24 of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
measure: AUC24-48 of Telavancin
timeFrame: At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michigan
name: Bruce A. Mueller, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gharibian KN, Lewis SJ, Heung M, Segal JH, Salama NN, Mueller BA. Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis. J Antimicrob Chemother. 2021 Dec 24;77(1):174-180. doi: 10.1093/jac/dkab370.