Preliminary Research On Two-step Dosing Of Imipenem/Cilastatin

Phase 4

• Conditions: Sepsis
• Interventions: Drug: Imipenem

• Registration Number: NCT02616354
• Lead Sponsor: Southeast University, China

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-01
• Status Verified: 2015-11
• Primary Completion: 2015-11
• Study First Submitted: 2015-11-13
• Study First Submitted QC: 2015-11-24
• Last Update Submitted: 2015-11-24
• Study First Posted: 2015-11-26
• Last Update Posted: 2015-11-26
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I	Imipenem	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).
Group II	Imipenem	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).

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC)	up to 9 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Kang Xu; 🇨🇳 Nanjing, Jiangsu, China