Clinical Trial: Safety & Efficacy of Daptomycin Versus Standard of Care (SOC) in 1 - 17 Year Olds With Staphylococcus Aureus Bacteremia (MK-3009-005)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Comparative Evaluation of the Safety and Efficacy of Daptomycin Versus Standard of Care in Pediatric Subjects One - Seventeen Years of Age With Bacteremia Caused by Stap

Brief Summary: The intent of this study is to describe the safety and efficacy of daptomycin versus standard of care (SOC) in pediatric participants aged 1-17 years with bacteremia caused by Staphylococcus aureus (S. aureus).

Detailed Summary:

S. aureus causes a series of invasive diseases in adults and children, including bacteremia. Infections due to S. aureus in children, particularly those due to methicillin resistant S. aureus (MRSA), are a growing world-wide public health concern.

Daptomycin, a cyclic lipopeptide antibacterial agent, shows rapid in vitro bactericidal activity with concentration-dependent killing for Gram-positive organisms, including S. aureus. Surveillance studies have demonstrated a daptomycin MIC90 of 0.5µg/ml for both methicillin-susceptible S. aureus (MSSA) and MRSA with >99% of MRSA isolates being categorized as susceptible by the Food and Drug Administration (FDA), European Committee of antimicrobial susceptibility testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) breakpoints (5). Clinical trials in adults demonstrated that daptomycin was safe and efficacious in complicated skin and skin structure infections (cSSSI) and bloodstream infections caused by S. aureus, including right-sided infective endocarditis (RIE). However, information on the safety and efficacy of daptomycin for use in children is lacking.

The intent of this study in children is to confirm the safety of daptomycin at mean steady state systemic exposures (AUC) similar to those reported for adults treated at 6 mg/kg for bacteremia.

Current Primary Outcome:

• Number of Participants With One or More Adverse Events (AEs) [ Time Frame: Administration of first dose through the last follow-up visit (up to 77 days) ]
  An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
• Number of Participants With One or More Serious Adverse Events (SAEs) [ Time Frame: Administration of first dose through the last follow-up visit (up to 77 days) ]
  An SAE is any adverse experience occurring at any dose that results in any of the following outcomes: death, life threatening experience, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is considered to be an important medical event.
• Percentage of Participants With Maximum Post-Baseline Creatine Phosphokinase (CPK) Elevations Above Upper Limit of Normal [ Time Frame: Baseline up to end of therapy visit (up to 49 days) ]
  Blood was drawn from baseline up to the end of therapy visit to determine the percentage of participants with maximum post-baseline CPK elevations above the upper limit of 500 Units Per Liter (U/L) .
• Percentage of Participants With Sustained CPK Elevations [ Time Frame: Baseline up to end of therapy visit (u
  
  

  Original Primary Outcome: Safety of daptomycin measured by the incidence of treatment-emergent adverse events, vital signs, echocardiogram (if performed) and clinical laboratory tests, use of concomitant medications,physical and neurological exam results. [ Time Frame: Administration of first dose through the last follow-up visit; an expected average of 9-11 weeks ]
  
  

  Current Secondary Outcome:

  • Percentage of Participants With Clinical Success at TOC/Safety Visit [ Time Frame: 7-14 days after the last dose of study medication (up to 56 days) ]
    Clinical success was determined by assessing resolution/improvement of signs and symptoms. An assessment of cure or improved is considered clinical success. Cure: resolution of clinically significant signs and symptoms associated with admission infection; no further antibiotic therapy is required for the primary infection under study. Improvement: partial resolution of clinical signs/symptoms of infection such that no further antibiotic therapy is required for the primary infection under study.
  • Percentage of Participants With Overall Success at TOC Visit [ Time Frame: 7-14 days after the last dose of study medication (up to 56 days) ]
    Overall success is based on microbiologic responses after initiating study drug and clinical response at TOC/Safety Visit. Overall outcome is a success if both clinical and microbiologic outcomes are successes. An assessment of cure or improved is considered clinical success. Microbiological Success: a participant for whom all baseline infecting pathogens were eradicated (presumed or documented) within 7 days from the start of study drug for uncomplicated bacteremia with no source of infection present, and 10 days for complicated bacteremia or when the source of infection has not been removed.
  • Trough Plasma Concentration of Daptomycin [ Time Frame: Days 3, 4, 5 or 6 of treatment at pre-dose ]
    Plasma concentrations of daptomycin were measured on Days 3 through 6 of IV dosing. Trough concentrations were collected 22 to 26 hours following the end of the previous day's end of infusion and before the next infusion. Concentrations below the limit of quantification were excluded.
  • Maximum Plasma Concentration (Cmax) of Daptomycin [ Time Frame: Days 3, 4, 5 or 6 of treatment at end of infusion ]
    Plasma concentrations of daptomycin were measured on Days 3 through 6 of IV dosing. Peak concentrations were collected up to 15 minutes following the end of infusion. Concentrations below the limit of quantification were excluded.
  
  
  

  Original Secondary Outcome: Efficacy of daptomycin will be based on Investigator's assessment of clinical response (cure, improved, failure or non-evaluable) at the Test of Cure (TOC) visit. [ Time Frame: EOT(after completion of i.v. or oral therapy, up to 6 weeks) and TOC (7-14 days after the last dose of study medication) ]
  
  Information By: Cubist Pharmaceuticals LLC
  

  Dates:
  Date Received: November 5, 2012
  Date Started: November 2012
  Date Completion:
  Last Updated: February 23, 2017
  Last Verified: February 2017