The Pharmacokinetics/Pharmacodynamics of High-dose Daptomycin in Patients With Septic Shock

Study Overview
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Brief Summary
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The first objective of this study was to characterize the pharmacokinetics and pharmacodynamics of daptomycin with a daily dose of 12mg/kg in septic shock patient; the second objective is to identify the optimal dosing scheme for daptomycin among patients with septic shock and to enhance therapeutic outcomes.

Detailed Description
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Daptomycin is a novel lipopeptide exhibiting concentration-dependent bactericidal activity against multidrug-resistant Gram-positive pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA). In recent years, daptomycin plays an important role in the treatment of septic shock. The pharmacokinetics of daptomycin is significant changed in patients with septic shock, it is proved that the recent dosage regiment comes with a low blood drug concentration and unsatisfactory outcome. Although the high-dose daptomycin shows safety and effectiveness in the treatment of critically ill patient, but still the pharmacokinetics and pharmacodynamics data is scant. So the purposes of this study is to characterize the pharmacokinetics and pharmacodynamics of daptomycin with a daily dose of 12mg/kg in septic shock patient; the second objective is to identify the optimal dosing scheme for daptomycin among patients with septic shock and to enhance therapeutic outcomes.

Official Title
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The Pharmacokinetics and Pharmacodynamics of High-dose Daptomycin in Patients With Septic Shock

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Daptomycin
* Other: determination of plasma concentration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years and ≤75 years confirmed or suspected bloodstream and soft tissue infections caused by a grampositive organism Exclusion Criteria: known hypersensitivity to daptomycin or product excipients documented or suspected pneumonia caused by a grampositive organism infection with a daptomycin-resistant organism presence or history of rhabdomyolysis signs or symptoms of myopathy with an elevation of creatine phosphokinase concentrations 6.pregnancy or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: daptomycin<br>Daptomycin for injection 10-12mg/kg/day,determination of plasma concentration | Drug: Daptomycin<br>* Drug: Daptomycin for Injection（Cubicin,AstraZeneca） dosage: 10-12mg/kg/day frequency: once a day duration: 14 days<br>* Other names: Cubicin;Other: determination of plasma concentration<br>* A maximum of 12 blood samples (1.5mL) were collected in Ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) tubes over a 6-dose administration sequence.Sampling was done prior to the administration of the first dose, at 30 minutes (end of infusion),and at 4,12,and 24 hours after the initial dose.Additional blood samples were collected at the end of infusion (peak) and prior to the subsequent dose (trough) for doses 2-5.After the sixth dose the blood samples were collected prior to the administration and at 4,and 24 hours after the end of infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve(AUC)/Minimum inhibitory concentration(MIC) |  | 6 days | 
| Peak concentration (Cmax)/Minimum inhibitory concentration(MIC) |  | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rate |  | 28 days |