Clinical trial NCT01012089: Study of the Pharmacokinetics of Daptomycin in Children With Renal Disease
Official title: Study of the Pharmacokinetics of Daptomycin in Children With Renal Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Bacterial Infection
Keywords: Hemodialysis
Peritoneal dialysis
Daptomycin
Pharmacokinetics
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2009-11-11
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 0, 0.5, 2, 3, 4.5 6, 24, and 48 hours post dose
measure: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC0-24)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, and 24 hours post dose
measure: Area Under the Concentration Time Curve From Time Zero to 48 Hours (AUC0-48)
timeFrame: 0, 0.5, 2, 3, 4.5 6, 24, and 48 hours post dose
measure: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-∞)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
measure: Volume of Distribution at Steady State (Vss)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
measure: Elimination Rate Constant (Ke)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
measure: Total Drug Clearance (CLtotal)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
measure: Drug Clearance Due to Dialysis (CLdialysis)
timeFrame: 0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: The Children's Hospital at the University of Oklahoma Medical Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Teresa V Lewis, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oklahoma
name: Martin A Turman, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: