Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)
multicenter, randomized, double blind study to describe the safety and efficacy of daptomycin (6 mg/kg q24h) with and without concomitant initial gentamicin combination therapy in the treatment of SAIE
Drug: daptomycin and gentamicin
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 4 Multicenter, Randomized, Double Blind Study to Describe the Efficacy and Safety of Cubicin® (Daptomycin for Injection) With and Without Initial Gentamicin Combination Therapy in the Treatment of S. Aureus Infective Endocarditis|
- Summary of Clinically Significant Increases in Serum Creatinine by Visit [ Time Frame: Baseline, EOT Visit, TOC ] [ Designated as safety issue: No ]The End of Treatment (EOT)/Early Termination (ET) visit occurred on the day that therapy was stopped or up to 2 days after the last dose of daptomycin. The Test of Cure (TOC)/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. The overall median duration of treatment was 13.0 days in both the daptomycin group and the combination therapy group. The definition of elevated serum creatinine at baseline is >3.0 mg/dL, and not elevated is ≤3.0 mg/dL. Clinically significant increases in serum creatinine is defined as an increase ≥0.5 mg/dL for patients with a baseline value ≤3.0 mg/dL or ≥1.0 mg/dL for patients with a baseline value >3.0 mg/dL.
- Summary of the Investigator's Assessment of Clinical Response at the TOC Visit [ Time Frame: TOC Visit ] [ Designated as safety issue: No ]TOC/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. Clinical response was assessed by the investigator as cure, improvement, failure, and unable to evaluate. Microbiological response, which was determined by the sponsor based on review of baseline and post-baseline culture results, included success, failure, and nonevaluable. TC=Treatment Cure; TF=Treatment Failure; TI=Treatment Improved.
|Study Start Date:||March 2008|
|Study Completion Date:||November 2011|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Active Comparator: Daptomycin Alone
daptomycin 6 mg/kg q24h for treatment of right-sided infective endocarditis
Intravenous (i.v.) 6 mg/kg q24h
Experimental: Daptomycin plus gentamicin
daptomycin 6 mg/kg q24h with concomitant initial gentamicin dosed for the first 2 days of therapy for the treatment of right-sided infective endocarditis
Drug: daptomycin and gentamicin
i.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin
Patients will be randomized to either of the following two treatment arms:
- Arm 1: daptomycin
- Arm 2: daptomycin with initial i.v. gentamicin
Patients who meet all the inclusion criteria and exhibit none of the exclusion criteria may be enrolled. Intravenous drug user (IVDU) patients may be randomized and study drug begun on the basis of two separate peripheral blood cultures positive for S. aureus obtained within 96 hours prior to the first dose of study drug.
The recommended minimum duration of treatment for daptomycin will be 28 days. The duration of treatment for gentamicin will be 3 days.
During study treatment, regular assessments (including weekly safety laboratory testing including CPK) will be performed. An End-of-Therapy (EOT) evaluation will be performed on the day of or 1-2 days after completion of daptomycin study drug or upon early termination (ET). All patients will have a post-therapy visit for Test of Cure (TOC)/Safety performed 21-28 days following the last dose of daptomycin study drug.
|United States, Colorado|
|Denver Health Medical Center|
|Denver, Colorado, United States, 80204|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|Wayne State University|
|Detroit, Michigan, United States, 48201|
|United States, Pennsylvania|
|Temple University School of Medicine|
|Philadelphia, Pennsylvania, United States, 19140|
|Study Director:||Paula Bokesch, M.D.||Cubist Pharmaceuticals|