Daptomycin as an Adjuvant Agent in the Treatment of Enterococcal Native Valve Endocarditis.

Study Overview
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Brief Summary
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The aim of this study is to determine the safety and efficacy of daptomycin when used as an adjuvant agent to standard care in the treatment of proven native valve Enterococcal endocarditis. Patients with this disease will be offered the option of receiving daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving. The hypothesis of this study is that daptomycin added to standard therapy for Enterococcal endocarditis is safe and efficacious. Patients who receive daptomycin + standard therapy will be compared to patients who receive standard therapy alone with respect to the following outcomes: Safety. The frequency of any Grade 3 or 4 toxicity (DAIDS scale) will be measured. The frequency of muscle toxicity or renal toxicity, as determined by predefined criteria. Efficacy. Clinical efficacy. Time to clearance of bacteremia Cure at 6 weeks following completion of antibiotic therapy Mortality at 6 weeks following completion of antibiotic therapy Microbiologic efficacy. Peak and trough serum bactericidal titers The minimum bactericidal concentration of Enterococci to daptomycin We expect to enroll 40 patients over 2 years.

Official Title
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Open Label Study to Assess the Efficacy and Safety of Daptomycin in Combination With Anti-Cell Wall Active Therapy in the Treatment of Enterococcal Endocarditis

Conditions
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Endocarditis, Bacterial

Intervention / Treatment
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* Drug: Daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or over Definite Enterococcal endocarditis, as defined by modified Duke criteria Able to complete follow-up 3 and 6 weeks following completion of intravenous antibiotic therapy Exclusion Criteria: Pregnancy or breast feeding Creatine phosphokinase levels over two times the upper limit of normal Renal insufficiency or dialysis requirement. Presence of chronic indwelling bloodstream catheters or foreign body devices suspected as primary or secondary sites of enterococcal infection unamenable to removal or replacement Inability to discontinue or abstain from use of a HMG CoA reductase inhibitor during the study period. Hypersensitivity to any of the study medications. Any condition that, in the investigator's opinion, may interfere with protocol compliance including, but not limited to, active substance abuse and/or dementia. Prosthetic valve endocarditis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daptomycin adjunctive group<br>Patients with enterococcal endocarditis who elect to receive daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving | Drug: Daptomycin<br>* daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis<br>* Other names: Cubicin;|
| No Intervention: standard of care<br>Patients with enterococcal endocarditis who elect to receive standard of care therapy as prescribed by their primary physician | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) | Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details | weekly | 
| Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | Number of Participants with creatine kinase elevation > 3x upper limit of normal or elevations of serum Cr >= 30% above baseline | weekly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enterococcus, Daptomycin, Endocarditis