Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
- Conditions
- Osteomyelitis
- Interventions
- Registration Number
- NCT00428844
- Lead Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Brief Summary
This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
- Subject must be between the ages of 18 and 80, inclusive
- Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
- Subject must have a positive microbiological identifier of staphylococci.
- If Subject is female of childbearing potential, must be willing to practice reliable birth control
- Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
- Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
- Subject has significant hepatic dysfunction
- Subject has a fungal or mycobacterial PJI
- Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
- Subject has an abnormal creatine phosphokinase (CPK) (elevated CPK level ≥ 2x ULN) at baseline as measured by central laboratory
- Subject is currently under treatment with chemotherapeutic agents excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer)
- Subject is pregnant, nursing, or lactating.
- Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Comparator nafcillin Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). Daptomycin 8 mg/kg daptomycin Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week). Comparator vancomycin Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). Daptomycin 6 mg/kg daptomycin Daptomycin (6 mg/kg every 24 hours \[q24h\]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week). Comparator teicoplanin Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). Comparator oxacillin Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week). Comparator flucloxacillin Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
- Primary Outcome Measures
Name Time Method Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L) From the 3rd day of therapy to 1 week post last dose (approximately week 7) Number of subjects with CPK \>500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
- Secondary Outcome Measures
Name Time Method Safety - Notable Laboratory Abnormalities From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30) Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
Overall Clinical Outcome Approximately 6 weeks post last dose (approximately week 12) The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.
Microbiological Response Approximately 6 weeks post last dose (approximately week 12) Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) Day 4 (steady state) The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss) Day 4 (steady state) The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Trial Locations
- Locations (26)
UAMS College of Medicine
🇺🇸Little Rock, Arkansas, United States
South Denver Infectious Disease Associates, PC
🇺🇸Englewood, Colorado, United States
Kane and Davis Associates
🇺🇸Washington, District of Columbia, United States
Infectious Disease Association of Tampa Bay
🇺🇸Tampa, Florida, United States
Idaho Falls Infectious Diseases, PLLC
🇺🇸Idaho Falls, Idaho, United States
Rush St. Luke's Medical Center
🇺🇸Chicago, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Sierra Infectious Disease
🇺🇸Reno, Nevada, United States
Dartmouth-Hitchcock Medical center
🇺🇸Lebanon, New Hampshire, United States
Scroll for more (16 remaining)UAMS College of Medicine🇺🇸Little Rock, Arkansas, United States