Daptomycin in the Treatment of Subjects With Infective Endocarditis or Bacteremia Due to S. Aureus

Condition(s) targeted: Bacterial Endocarditis; Bacteremia

Intervention: daptomycin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Cubist Pharmaceuticals

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).

Official title: A Phase 3, Multicenter, Randomized, Open-Label, Comparative Study to Assess the Safety and Efficacy of Daptomycin Compared to Conventional Therapy In the Treatment of Subjects With Infective Endocarditis or Bacteremia Due to Staph Aureus

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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 outcome:

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 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 demonstrate that survival rates are similar between daptomycin and comparator 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.

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 g/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)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Starting date: August 2002
Ending date: February 2005
Last updated: February 7, 2007