Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci

This study has been completed.
Sponsor:
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00428844
First received: January 26, 2007
Last updated: May 13, 2011
Last verified: May 2011

January 26, 2007
May 13, 2011
January 2007
March 2010   (final data collection date for primary outcome measure)
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L) [ Time Frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7) ] [ Designated as safety issue: Yes ]
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.
Not Provided
Complete list of historical versions of study NCT00428844 on ClinicalTrials.gov Archive Site
  • Safety - Notable Laboratory Abnormalities [ Time Frame: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
Not Provided
 
Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
A Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Osteomyelitis
  • Drug: daptomycin
    6 mg/kg
    Other Name: Cubicin
  • Drug: daptomycin
    8 mg/kg
    Other Name: Cubicin
  • Drug: vancomycin
    1 gram
    Other Name: Vancocin
  • Drug: teicoplanin
    6 mg/kg; used only at UK sites
    Other Name: Targocid
  • Drug: nafcillin
    1-2 gram
    Other Name: Unipen
  • Drug: oxacillin
    1-2 gram
    Other Name: Bactocill
  • Drug: flucloxacillin
    1-2 mg
    Other Name: Fluclox
  • Experimental: Daptomycin 6 mg/kg
    Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
    Intervention: Drug: daptomycin
  • Experimental: Daptomycin 8 mg/kg
    Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
    Intervention: Drug: daptomycin
  • Active Comparator: Comparator
    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).
    Interventions:
    • Drug: vancomycin
    • Drug: teicoplanin
    • Drug: nafcillin
    • Drug: oxacillin
    • Drug: flucloxacillin
Byren I, Rege S, Campanaro E, Yankelev S, Anastasiou D, Kuropatkin G, Evans R. Randomized controlled trial of the safety and efficacy of Daptomycin versus standard-of-care therapy for management of patients with osteomyelitis associated with prosthetic devices undergoing two-stage revision arthroplasty. Antimicrob Agents Chemother. 2012 Nov;56(11):5626-32. doi: 10.1128/AAC.00038-12. Epub 2012 Aug 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
75
June 2010
March 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Russian Federation,   United Kingdom
 
NCT00428844
DAP-OST-06-02
Yes
Ed Campanaro, VP Clinical Operations, Cubist Pharmaceuticals
Cubist Pharmaceuticals
Not Provided
Study Director: Alistair Wheeler, MD Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA
Cubist Pharmaceuticals
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP