Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia

• Status: Terminated
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cubist Pharmaceuticals LLC
• Treatments: Daptomycin; Vancomycin

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.