Study of the Pharmacokinetics of Daptomycin in Children With Renal Disease

Conditions

Bacterial Infection, Chronic Kidney Disease

Keywords

Hemodialysis, Peritoneal dialysis, Daptomycin, Pharmacokinetics

Brief summary

The purpose of this study is to: 1. Study the pharmacokinetics and safety of daptomycin in children on hemodialysis (HD) and peritoneal dialysis (PD). 2. Determine urine, HD and PD clearance of daptomycin.

Detailed description

Infectious and sepsis events are one of the most common complications in children with chronic kidney disease. The incidence is highest in children with an access for dialysis, especially in those with catheters. Staphylococcal species account for more than 50% of access infections (ranging from 58-77%). Failure to clear the infection results in loss of dialysis access. Daptomycin is a new antibiotic that provides coverage against most gram positive bacteria including methicillin-resistant staphylococci, vancomycin-intermediate Staphylococcus aureus, and vancomycin-resistant enterococci. The pharmacokinetics of daptomycin in children on dialysis, a group of patients who may need the medication the most, remains unknown. Children on HD or PD with suspected or confirmed infections due to gram-positive bacteria and who are concurrently treated with standard of care antibiotics will be considered for this study. Each patient will be given a onetime dose of Cubicin (daptomycin). After receiving daptomycin, serial blood samples along with dialysis effluent and urine (obtained from non-anuric patients) will be collected to evaluate the pharmacokinetic profile of the drug.

Related papers

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Interventions

DRUGDaptomycin

Daptomycin IV 5 mg/kg one time dose

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

No

Inclusion criteria

* Children who are between 12-17 years of age who are either on HD or PD and whom the Pediatric Nephrology Section of the OU Children's Physicians Clinics provide care. * In addition to children on chronic HD and PD therapy, patients newly initiated on HD and PD will also be recruited for this study. * Patients with suspected or confirmed cases of dialysis related infection from gram-positive bacteria and who are receiving standard of care antibiotics. * Patients will be eligible for enrollment if they were admitted as an inpatient to the Children's hospital or as an outpatient to the dialysis clinic

Exclusion criteria

* Patients \> 17 years of age * Patients \< 12 years of age * Total amount of blood drawn as part of standard of care and for pharmacokinetic analysis exceeds 3 ml/kg over an 8 week period * Taking an HMG CoA reductase inhibitor within 7 days of daptomycin administration * Having used daptomycin in the 30 days preceding study entry * Participating in any experimental procedure in the 30 days preceding study * A history of muscular disease or neurological disease * Baseline creatine phosphokinase (CPK) values equal to or greater than 1.5 times the upper limit of normal (normal range 65-370 IU/L) * Hemoglobin \< 9 g/dl * Hemodynamic instability within 72 hours before study enrollment * Female subjects with a positive pregnancy test or failure to take a pregnancy test

Design outcomes

Primary

Measure	Time frame	Description
Volume of Distribution at Steady State (Vss)	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose	The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug
Maximum Plasma Concentration (Cmax)	0, 0.5, 2, 3, 4.5 6, 24, and 48 hours post dose	—
Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC0-24)	0, 0.5, 2, 3, 4.5, 6, and 24 hours post dose	—
Area Under the Concentration Time Curve From Time Zero to 48 Hours (AUC0-48)	0, 0.5, 2, 3, 4.5 6, 24, and 48 hours post dose	—
Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-∞)	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose	—
Elimination Rate Constant (Ke)	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose	—
Total Drug Clearance (CLtotal)	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose	The rate at which a drug substance is removed from the body
Drug Clearance Due to Dialysis (CLdialysis)	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose	The rate at which a drug substance is removed from the body due to dialysis therapy

Countries

United States

Participant flow

Participants by arm

Arm	Count
Daptomycin Hemodialysis Daptomycin: Daptomycin IV 5 mg/kg one time dose to patient receiving intermittent hemodialysis on MWF	3
Daptomycin Peritoneal Dialysis Daptomycin: Daptomycin IV 5 mg/kg one time dose to patient receiving continuous cycling peritoneal dialysis	3
Total	6

Baseline characteristics

Characteristic	Daptomycin Peritoneal Dialysis	Daptomycin Hemodialysis	Total
Age, Categorical <=18 years	3 Participants	3 Participants	6 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	13.7 years	15.3 years	14.5 years
Region of Enrollment United States	3 participants	3 participants	6 participants
Sex: Female, Male Female	1 Participants	0 Participants	1 Participants
Sex: Female, Male Male	2 Participants	3 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3
other Total, other adverse events	0 / 3	0 / 3
serious Total, serious adverse events	0 / 3	0 / 3