Preliminary Research On Two-step Dosing Of Imipenem/Cilastatin

Study Overview
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Brief Summary
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Explore Imipenem/Cilastatin two-step dosing compared to 2 hours infusion in patients with severe whether can obtain better results of the pharmacokinetic/pharmacodynamic, for clinical rational use of antimicrobial agents, and provide theoretical support for optimizing dosage regimen.

Detailed Description
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Compared with Imipenem/Cilastatin 2 hours continuous dosing method and two-step dosing method (0.5 hours before enter half dose, after 1.5 hours, the other half of the input dose) of blood drug concentration in the body than the minimal inhibitory concentrations (MIC) pathogens percent of dosing interval duration (100% fT > MIC), blood drug concentration in the body more than 4 times the minimal inhibitory concentrations (MIC) pathogens percent of dosing interval duration (100% fT > 4 MIC), blood drug concentration peak and the ratio of the minimal inhibitory concentrations (MIC) pathogens (Cmax/MIC), blood drug concentration (Tmax) used in the peak time, used to guide clinical patients with severe infection of Imipenem/Cilastatin usage.

Official Title
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Preliminary Research On Two-step Dosing Of Imipenem/Cilastatin

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Imipenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sepsis or severe sepsis or severe infections in the previous 48 hours treatment with imipenem/cilastatin (recommended by hospital microbiologists) expected duration of hospital stays in the ICU ≥ 72 h from recruitment recruited patients agreed to participate in this trial, and had set up a signed informed consent Exclusion Criteria: with an allergy to carbapenems or with an adverse drug reaction to imipenem acute or chronic renal failure assessed by serum creatinine concentrations > 280 μmol/L (or creatinine clearance <20mL/min) or those requiring continuous renal replacement therapy drug or alcohol abuse Pregnant and lactant women patients near to death

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I<br>Group I received intravenous imipenem/cilastatin 1 g every 8 h (q8h) or 0.5g every 6 h (q6h) with optimized two-step infusion therapy (OTIT; rapid first-step infusion in 30 min and slow second-step infusion above 1.5 hours) Group I is more informative than Group II from PK parameters(%T>MIC,AUC/MIC). | Drug: Imipenem<br>* Patients in group I received a dose of imipenem/cilastatin 1g each every 8 hours or 0.5g every 6 hours optimized two-step infusion therapy (rapid first-step infusion in 30 min and slow second-step infusion above 1.5 hours)<br>* Other names: Optimized two-step infusion therapy;|
| Placebo Comparator: Group II<br>group II received intravenous imipenem/cilastatin 1g q8h or 0.5g q6h with extended infusion therapy (2-hours continuous infusion in a constant speed). Group I is more informative than Group II from PK parameters(%T>MIC,AUC/MIC). | Drug: Imipenem<br>* Patients in group I received a dose of imipenem/cilastatin 1g each every 8 hours or 0.5g every 6 hours optimized two-step infusion therapy (rapid first-step infusion in 30 min and slow second-step infusion above 1.5 hours)<br>* Other names: Optimized two-step infusion therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) |  | up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration | immediately prior to imipenem/cilastatin administration (time 0 min) and at 30 min, 1h, 2h, 4h, 6h and 8h after administration of the infusion | up to 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics; pharmacodynamic; imipenem; sepsis