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.
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 82
- Primary Endpoint
- Number of Participants With One or More Adverse Events (AEs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Daptomycin - 12 to 17 year olds
Participants ages 12-17 years old were administered daptomycin 7 mg/kg infused once daily, intravenously (IV), over 30 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-42 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).
Intervention: Daptomycin (Drug)
Comparator - 12 to 17 year olds
Participants ages 12-17 years old received IV vancomycin or semi-synthetic penicillin or first-generation cephalosporins or clindamycin, given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-42 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.
Intervention: Comparator (Drug)
Daptomycin - 7 to 11 year olds
Participants ages 7 to 11 years old were administered daptomycin 9 mg/kg, infused once daily, IV over 30 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).
Intervention: Daptomycin (Drug)
Daptomycin - 1 to 6 year olds
Participants ages 1 to 6 years old were administered daptomycin 12 mg/kg, infused once daily, IV over 60 minutes; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. After conclusion of IV therapy, can continue on oral therapy (not daptomycin, but at discretion of investigator).
Intervention: Daptomycin (Drug)
Comparator - 7 to 11 year olds
Participants ages 7-11 years old received IV vancomycin, or semi-synthetic penicillin, or first-generation cephalosporins, clindamycin; given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.
Intervention: Comparator (Drug)
Comparator - 1 to 6 year olds
Participants ages 1-6 years old received IV vancomycin, or semi-synthetic penicillin, or first-generation cephalosporins, clindamycin; given as per local guidelines or site-specific prescribing information; therapy duration (uncomplicated bacteremia) = 5-28 days, therapy duration (complicated bacteremia) = 7-28 days. IV comparator and subsequent oral therapy were at the discretion of the investigator.
Intervention: Comparator (Drug)
Outcomes
Primary Outcomes
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 (up to 44 days)
Blood was drawn from baseline up to the end of therapy visit to determine the percentage of participants with sustained CPK elevations, defined as two consecutive post-baseline values above the upper limit of normal (ULN)
Number of Participants With Abnormal Focused (Peripheral) Neurological Assessments at Test of Cure (TOC)
Time Frame: TOC Safety Visit (up to 56 days)
Focused neurological examinations were done at the TOC/Safety Visit. These examinations include assessments of sensation, pupillary reflex and tracking, peripheral reflexes (biceps, patellar tendon, ankle jerk and plantar response), muscle tone and strength (upper and lower limbs), coordination (finger to nose) and tremor of the hands/fingers.
Secondary Outcomes
- Maximum Plasma Concentration (Cmax) of Daptomycin(Days 3, 4, 5 or 6 of treatment at end of infusion)
- Trough Plasma Concentration of Daptomycin(Days 3, 4, 5 or 6 of treatment at pre-dose)
- Percentage of Participants With Clinical Success at TOC/Safety Visit(7-14 days after the last dose of study medication (up to 56 days))
- Percentage of Participants With Overall Success at TOC Visit(7-14 days after the last dose of study medication (up to 56 days))