Bacteremia, Bacterial Endocarditis
Conditions
Keywords
Gram-positive bacterial infections, Staph Aureus, endocarditis, bacteremia, Cubist
Brief summary
The purpose of this study is to compare the safety and efficacy of daptomycin, an antibiotic, to standard therapy in subjects who have infective endocarditis or bacteremia due to Staphylococcus aureus (S. aureus).
Detailed description
Even with prompt treatment, Staphylococcus aureus Infective Endocarditis (IE) continues to be associated with significant morbidity and mortality indicating a need for new therapeutic approaches. In vitro, daptomycin is rapidly bactericidal, with concentration-dependent killing, and MIC90 of 0.5 microgram/ml for S. aureus; in clinical studies, daptomycin appears to be well tolerated and can be administered once every 24 hours by i.v. infusion. These characteristics suggest it should be clinically and microbiologically effective in the treatment of serious S. aureus infections, including IE and bacteremia Comparison: standard of care (Vancomycin or Semi-synthetic Penicillin with adjunct gentamicin)
Interventions
DRUGdaptomycin
Sponsors
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented S. aureus bacteremia within 2 calendar days of the first dose of study medication
Exclusion criteria
* Subjects with a creatinine clearance of less than 30 ml/min * Subjects with pneumonia * Pregnant, nursing, or lactating * Documented history of allergy or intolerance to penicillin or vancomycin * Subjects with osteomyelitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate that daptomycin is not inferior to comparator in the treatment of S. aureus bacteremia and IE as assessed by the Independent External Adjudication Committee (IEAC) Outcome at Test of Cure (TOC) in the Intention-to-Treat (ITT) population. | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome at EOT and TOC in the Per Protocol (PP) population. | — |
| To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome for each of the diagnoses defined by the IEAC at EOT in the ITT population. | — |
| To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome for each of the diagnoses defined by the Investigator at EOT in the ITT population. | — |
| To compare microbiologic eradication rates between daptomycin and comparator. | — |
| To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome at End of Treatment (EOT) in the ITT population. | — |
| To evaluate the safety of daptomycin as compared to comparator in the safety population. | — |
| To assess the pharmacokinetics of daptomycin. | — |
| To compare the pharmacoeconomic impact of daptomycin with that of comparator. | — |
| To demonstrate that survival rates are similar between daptomycin and comparator in the ITT population. | — |
Outcome results
None listed