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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02392208

Enrollment

Registered

2015-03-18

Start date

2015-07-31

Completion date

2016-03-31

Last updated

2017-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

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.

Interventions

DRUGTelavancin

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

PROCEDUREPharmacokinetic Blood Sampling

Blood samples are collected to assess telavancin plasma concentrations.

Study design

Allocation

NON_RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

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

Countries

United States

Participant flow

Recruitment details

Recruitment commenced on 07/07/15 at the University of Michigan outpatient dialysis clinics. The final participant enrolled in the study on 02/09/16.

Pre-assignment details

All 8 participants followed a crossover study design and completed study arm 1 (telavancin before hemodialysis) followed by a 14-day minimum wash out then study arm 2 (telavancin after hemodialysis).

Participants by arm

Arm	Count
All Study Participants Period 1: Telavancin Before Hemodialysis Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin (5 mg/kg) administered intravenously (IV) before their normally scheduled hemodialysis session. Blood samples are collected over a 48-hour period to assess telavancin plasma concentrations. Period 2: Telavancin After Hemodialysis After a minimum 14-day period, participants from Period 1 receive another dose of telavancin (5 mg/kg). This dose is administered intravenously (IV) after the participant's normally scheduled hemodialysis session. Blood samples are collected over a 48-hour period to assess telavancin plasma concentrations.	8
Total	8

Arm

Count

All Study Participants

Period 1: Telavancin Before Hemodialysis Stage 5 Chronic Kidney Disease patients receive a single dose of telavancin (5 mg/kg) administered intravenously (IV) before their normally scheduled hemodialysis session. Blood samples are collected over a 48-hour period to assess telavancin plasma concentrations. Period 2: Telavancin After Hemodialysis After a minimum 14-day period, participants from Period 1 receive another dose of telavancin (5 mg/kg). This dose is administered intravenously (IV) after the participant's normally scheduled hemodialysis session. Blood samples are collected over a 48-hour period to assess telavancin plasma concentrations.

Total

Baseline characteristics

Characteristic	All Study Participants
Age, Continuous	47 years STANDARD_DEVIATION 20
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8
other Total, other adverse events	0 / 8	0 / 8
serious Total, serious adverse events	1 / 8	1 / 8