Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia
Condition: Endocarditis, Bacterial; Infective Endocarditis
MeSH terms: Bacteremia; Endocarditis, Bacterial; Endocarditis
Intervention: daptomycin; vancomycin
Intervention description: daptomycin 10 mg/kg IV every 24 hours; Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Intervention MeSH terms: Vancomycin; Daptomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gram-positive bacterial infections; Staph Aureus; Bacteremia; MRSA; Infective Endocarditis; Right-sided Infective endocarditis; SABIE; SAIE; RIE

Summary:

      The overall goals of this study are to compare the safety and efficacy of daptomycin
      monotherapy 10 mg/kg/day and vancomycin monotherapy dosed to achieve vancomycin trough levels
      of 15 to 20 μg/mL for the treatment of methicillin-resistant S. aureus bacteremia (MRSA),
      including right-sided infective endocarditis (RIE).
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Written informed consent has been obtained;

          -  ≥18 years of age;

          -  Suspected MRSA bacteremia determined by clinical judgment or 2 sets of positive blood
             cultures;

          -  Increased risk for an MRSA infection

        EXCLUSION CRITERIA:

          -  Received >48 hours of vancomycin therapy in the 7 days prior to enrollment;

          -  Received any systemic antibacterial agents potentially effective against MRSA in the 7
             days prior to enrollment;

          -  Anticipated requirement of antibiotics potentially effective against MRSA;

          -  High likelihood of left-sided infective endocarditis (LIE);

          -  Known/suspected polymicrobial bacteremia or infection including Gram-negative
             infections;

          -  Known pneumonia, osteomyelitis, or meningitis;

          -  Intravascular foreign material unless material intended removed within 3 days;

          -  Prosthetic heart valve;

          -  Cardiac decompensation, valve damage, or both such that high likelihood of valve
             replacement surgery within first 3 days of study drug treatment;

          -  Moribund clinical condition such that death likely within first 3 days of study drug
             treatment;

          -  Shock or hypotension or oliguria unresponsive to fluids after 4 hours;

          -  Received investigational drug within 30 days of study entry

          -  Received statins or other therapy with associated with rhabdomyolysis within 2 days of
             study entry;

          -  History of significant allergy or intolerance to vancomycin or daptomycin

          -  Infecting pathogen with confirmed reduced susceptibility to vancomycin;

          -  Infecting pathogen with confirmed reduced susceptibility to daptomycin

          -  Creatinine clearance <30 mL/min (Cockcroft-Gault equation actual body weight)

          -  Serum creatine phosphokinase (CPK) ≥500 U/L

          -  Alanine transaminase (ALT) or aspartate aminotransferase (AST) >5 X ULN;

          -  Total bilirubin ≥3.0 mg/dL;

          -  Severe neutropenia or expected development severe neutropenia during study;

          -  Known or suspected HIV infection with a CD4+ T-cell count <200/μL;

          -  Unlikely to comply with study procedures or return for evaluations;

          -  Body Mass Index (BMI) ≥40 kg/m2;

          -  Pregnant or nursing;

          -  Female of childbearing potential not willing to practice barrier methods of birth
             control.

        CONTINUATION CRITERIA:

          -  Fulfills A or B or both: A) Confirmed complicated MRSA bacteremia B) Possible or
             definite RIE caused by MRSA according to modified Duke criteria;

          -  Infecting S. aureus strain susceptible to vancomycin;

          -  Infecting S. aureus strain susceptible to daptomycin;

          -  Appropriate treatment of any foci of infection within first 3 days of study;

          -  Removal of any intravascular foreign material not allowed per inclusion criteria
             within first 3 days of study;

          -  Removal of any percutaneous or implanted catheters not allowed per inclusion criteria
             within first 3 days of study.