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

NCT02392208 | Completed Phase 4 Results

• 1 other identifier: HUM00095470
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• AUC0-24 of Telavancin

  At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48

• AUC24-48 of Telavancin

  At hours post dose: 0, 1, 1.5, 3, 6.5, 8, 24, 48

Study Arms (2)

Telavancin Before Hemodialysis

OTHER

Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin before their normally scheduled hemodialysis session.

Drug: Telavancin; Procedure: Pharmacokinetic Blood Sampling

Telavancin After Hemodialysis

OTHER

Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin immediately after their normally scheduled hemodialysis session.

Drug: Telavancin; Procedure: Pharmacokinetic Blood Sampling

Interventions

Telavancin DRUG

A single 5 mg/kg dose of telavancin is administered intravenously (IV).

Also known as: Vibativ

Telavancin After Hemodialysis; Telavancin Before Hemodialysis

Pharmacokinetic Blood Sampling PROCEDURE

Blood samples are collected to assess telavancin plasma concentrations.

Also known as: PK Sampling

Telavancin After Hemodialysis; Telavancin Before Hemodialysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• Theravance Biopharma: collaborator

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 34613416 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic

Interventions

telavancin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Bruce A. Mueller
• Organization: University of Michigan

muellerb@med.umich.edu

734-763-6629

Study Officials

• Bruce A. Mueller, PharmD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Associate Dean of Academic Affairs, College of Pharmacy

Study Record Dates

• First Submitted: March 12, 2015
• First Posted: March 18, 2015
• Study Start: July 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 4, 2017
• Results First Posted: March 30, 2017

Record last verified: 2017-03

Locations

US (1)