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

NCT ID: NCT01728376

Last Updated: 2018-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-29
• Study Completion Date: 2016-01-20

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.

Conditions

Bacteremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Daptomycin

Intervention Type: DRUG

Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

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.

Group Type: ACTIVE_COMPARATOR

Comparator

Intervention Type: DRUG

Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin: administered per standard of care. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

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).

Group Type: EXPERIMENTAL

Daptomycin

Intervention Type: DRUG

Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

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).

Group Type: EXPERIMENTAL

Daptomycin

Intervention Type: DRUG

Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

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.

Group Type: ACTIVE_COMPARATOR

Comparator

Intervention Type: DRUG

Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin: administered per standard of care. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

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.

Group Type: ACTIVE_COMPARATOR

Comparator

Intervention Type: DRUG

Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin: administered per standard of care. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

Interventions

Daptomycin

Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

Intervention Type: DRUG

Comparator

Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin: administered per standard of care. Participants may be switched to oral therapy following completion of IV study drug administration provided they showed clear clinical improvement and the pathogen was susceptible to an oral agent.

Intervention Type: DRUG

Other Intervention Names

Cubicin

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 29406465 (View on PubMed)

Other Identifiers

DAP-PEDBAC-11-02

Identifier Type: OTHER

Identifier Source: secondary_id

3009-005

Identifier Type: -

Identifier Source: org_study_id