Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia
- Conditions
- Endocarditis, BacterialInfective Endocarditis
- Interventions
- Registration Number
- NCT00695903
- Lead Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Brief 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).
- Detailed Description
Patients who meet all inclusion criteria and exhibit none of the exclusion criterial will be randomized to one of two treatment arms:
1. daptomycin Intravenously (IV) 10 mg/kg every 24 hours
2. vancomycin IV dosed to maintain trough levels of 15 to 20 μg/mL.
The suggested duration of therapy with daptomycin or vancomycin will be 28 days (or up to 42 days if clinically indicated). Dose adjustments for both drugs will be made by an unblinded pharmacist at each site. To minimize the duration with which patients are treated with antibacterial agents effective against S. aureus prior to enrollment, patients with suspected MRSA bacteremia will be enrolled pending definitive culture results. Suspected MRSA bacteremia will be defined clinically or as initial blood cultures that grow Gram-positive cocci and that were obtained from a patient at increased risk for methicillin-resistant S. aureus infections. However, only patients with confirmed MRSA bacteremia or right-sided infective endocarditis will remain in the study and be evaluated for efficacy. During treatment, regular assessments will be performed. An End-of Therapy (EOT) will be performed 1-3 days after stopping therapy or upon Early Termination (ET). All patients will have a post therapy visit for Test of Cure (TOC) performed 35-49 days following last dose of study drug.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description daptomycin 10 mg/kg daptomycin Daptomycin 10 mg/kg IV every 24 hours vancomycin high-dose vancomycin Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days) Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.
Number of Participants With Elevated Serum Creatinine On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days) Number of participants with treatment-emergent serum creatinine increases ≥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) by the EOT visit.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment Cure at Test of Cure (TOC)/Safety Visit Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8) Investigator's assessment of clinical response. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.
Number of Participants With Treatment Cure at End of Therapy (EOT) Visit End of Therapy (median day 12 and 6.5 in daptomycin and vancomycin modified intent-to treat population, respectively) Investigator's assessment of treatment cure. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.
Trial Locations
- Locations (2)
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States