Clinical trial NCT01728376: Safety & Efficacy of Daptomycin Versus Standard of Care (SOC) in 1 - 17 Year Olds With Staphylococcus Aureus Bacteremia (MK-3009-005)
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 Staphylococcus Aureus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bacteremia
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2012-11-19
Enrollment: 82
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: Inclusion Criteria:

To be included in this study, participants must:

* Sign a parental consent form; if appropriate, sign an assent form
* Be between 1 and 17 years of age
* Have proven or probable bacteremia caused by S. aureus based on the traditional culture result, rapid diagnostic test or Gram stain
* If female of childbearing potential, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study
* If male, must take appropriate measures to not get partner pregnant
* Able to comply with the protocol requirements

Exclusion Criteria:

Participants will not be allowed into the study if they:

* Have received a certain amount of antibacterial therapy specific for current bacteremia unless it is demonstrated that the organism is resistant to the given antibacterial;
* Anticipate to require other antibiotics that may be potentially effective against S. aureus;
* Have shock or hypotension unresponsive to standard therapy;
* Have received an investigational product or have participated in an experimental procedure within 30 days;
* Have an intolerance or hypersensitivity to daptomycin;
* Have renal insufficiency;
* Have prior history or current evidence of muscle damage (rhabdomyolysis; significant CPK elevation);
* Have history of clinically significant muscular disease, nervous system or seizure disorder, including unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barré or spinal cord injury;
* Have S. aureus pneumonia, empyema, meningitis, or endocarditis

Primary outcomes:
measure: Number of Participants With One or More Adverse Events (AEs)
timeFrame: Administration of first dose through the last follow-up visit (up to 77 days)
measure: Number of Participants With One or More Serious Adverse Events (SAEs)
timeFrame: Administration of first dose through the last follow-up visit (up to 77 days)
measure: Percentage of Participants With Maximum Post-Baseline Creatine Phosphokinase (CPK) Elevations Above Upper Limit of Normal
timeFrame: Baseline up to end of therapy visit (up to 49 days)
measure: Percentage of Participants With Sustained CPK Elevations
timeFrame: Baseline up to end of therapy visit (up to 44 days)
measure: Number of Participants With Abnormal Focused (Peripheral) Neurological Assessments at Test of Cure (TOC)
timeFrame: TOC Safety Visit (up to 56 days)
Secondary outcomes:
measure: Percentage of Participants With Clinical Success at TOC/Safety Visit
timeFrame: 7-14 days after the last dose of study medication (up to 56 days)
measure: Percentage of Participants With Overall Success at TOC Visit
timeFrame: 7-14 days after the last dose of study medication (up to 56 days)
measure: Trough Plasma Concentration of Daptomycin
timeFrame: Days 3, 4, 5 or 6 of treatment at pre-dose
measure: Maximum Plasma Concentration (Cmax) of Daptomycin
timeFrame: Days 3, 4, 5 or 6 of treatment at end of infusion
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Arrieta AC, Bradley JS, Popejoy MW, Bensaci M, Grandhi A, Bokesch P, Glasser C, Du L, Patino H, Kartsonis NA. Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard-of-care in Pediatric Patients With Staphylococcal Bacteremia. Pediatr Infect Dis J. 2018 Sep;37(9):893-900. doi: 10.1097/INF.0000000000001926.