Study of the Pharmacokinetics of Daptomycin in Children With Renal Disease

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Bacterial Infection
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73013
      • The Children's Hospital at the University of Oklahoma Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daptomycin; Pediatric patients on hemodialysis or peritoneal dialysis with suspected or confirmed infection and who were receiving standard of care antibiotics were also eligible to receive a single dose of daptomycin 5mg/kg IV. Serial blood draws were obtained to assess daptomycin pharmacokinetics	Drug: Daptomycin; Daptomycin IV 5 mg/kg one time dose; Other Names: Cubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Volume of Distribution at Steady State (Vss)	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	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)	The rate at which a drug substance is removed from the body	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose
Drug Clearance Due to Dialysis (CLdialysis)	The rate at which a drug substance is removed from the body due to dialysis therapy	0, 0.5, 2, 3, 4.5, 6, 24, and 48 hours post dose

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Cubist Pharmaceuticals LLC
• Investigators: Principal Investigator: Teresa V Lewis, Pharm.D., University of Oklahoma; Principal Investigator: Martin A Turman, M.D., Ph.D., University of Oklahoma

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 9, 2009
• First Submitted That Met QC Criteria: November 10, 2009
• First Posted (Estimate): November 11, 2009

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hemodialysis; Peritoneal dialysis; Daptomycin
• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Renal Insufficiency; Bacterial Infections and Mycoses; Kidney Diseases; Renal Insufficiency, Chronic; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 2375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED