Safety and Efficacy Study of Daptomycin When Compared to Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis
The purpose of the study is to determine whether daptomycin is effective and safe in the treatment of pediatric subjects with Acute Hematogenous Osteomyelitis (AHO) when compared to vancomycin or nafcillin (or β-lactam equivalent).
Acute Hematogenous Osteomyelitis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Multicenter, Randomized, Double-Blinded Comparative Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Daptomycin Versus Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis Due to Gram-Positive Organisms|
- Efficacy of daptomycin measured by clinical improvement in the 3 general categories of Pain, Inflammation, and Limb Function based on the Investigator's overall assessment of severity of each of the symptom categories. [ Time Frame: Study day 5 ] [ Designated as safety issue: No ]The Investigator will assess the general categories and clinical symptom parameters of AHO once at baseline; twice daily while subject is hospitalized and receiving IV study drug.
- Efficacy of daptomycin versus comparator in pediatric subjects with AHO [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - Test of Cure (21-35 days after last dose of IV study drug) ] [ Designated as safety issue: No ]
- Clinical improvement as composite end point of pain, inflammation, limb function, body temperature, and C-reactive protein measured at End of IV, End of Therapy, and Test of Cure.
- Microbiological outcome at Test of Cure
- Microbiological outcome by baseline pathogen at Test of Cure
- Sustained clinical improvement at End of Therapy and Test of Cure
- Safety of daptomycin [ Time Frame: The first dose of IV study drug - the final follow-up visit at 6 months ] [ Designated as safety issue: Yes ]Measured as incidence of Adverse events (AEs), serious adverse events (SAEs), deaths, and discontinuations due to AEs; changes in vital signs and focused neurological examinations; laboratory evaluations.
- The pharmacokinetics of daptomycin in pediatric subjects with AHO [ Time Frame: Study Day 3 ] [ Designated as safety issue: No ]Blood samples will be collected to measure the plasma concentrations of daptomycin.
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Intervention Drug: Daptomycin
IV daptomycin dosed at 7,9, or 12 mg/kg infused over 60 minutes ± 10 minutes once daily followed by 3 dummy infusions q6h infused over 60 (± 10) min to maintain the blind.
Active Comparator: Vancomycin or nafcillin (or β-lactam equivalent)
IV vancomycin, 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour) or IV nafcillin (or β-lactam equivalent) at 100-200 mg/kg/day, in divided doses infused over 60 (± 10) min q6h (± 1 hour)
|Drug: Vancomycin Drug: nafcillin|
Acute hematogenous osteomyelitis is a common problem in the pediatric population, affecting approximately 5/10,000 children each year and accounting for approximately 1% of all pediatric hospitalizations. In children, osteomyelitis arises from bacteremic seeding of the bone metaphysis.
Daptomycin, is a cyclic lipopeptide antibacterial active against most clinically significant gram-positive pathogens including drug-resistant strains such as MRSA and MSSA. Daptomycin has proven clinical efficacy in adults in the treatment of cSSSI caused by aerobic gram-positive pathogens and the treatment of S. aureus bloodstream infections (bacteremia; SAB), including those complicated by right-sided infective endocarditis, caused by MSSA and MRSA. Although not indicated for osteomyelitis, daptomycin has been successfully used to treat osteoarticular infections in adults and children as salvage therapy and at medical centers with increasingly high rates of vancomycin resistant organisms.
In addition, more comparative clinical trials are needed in pediatric AHO to better elucidate the optimal treatment regimen and clinical response.