Preliminary Research On Two-step Dosing Of Imipenem/Cilastatin (PROTDOI)

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.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Drug: Imipenem

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 Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Kang Xu
      • Contact: Kang Xu; Phone Number: +86 15851836872; Email: xukangyc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I; 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; 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); Other Names: Optimized two-step infusion therapy
Placebo Comparator: Group II; 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; 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); Other Names: Optimized two-step infusion therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK/PD indices	Time>MIC (∫T>MIC) and 4×MIC (∫T>4×MIC)	up to 9 moths

Collaborators and Investigators

• Sponsor: Southeast University, China
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Huang Y, Xu K, Zhan Y, Zha X, Liu S, Xie J, Liu L, Li Q, Shao H, Yang Y. Comparable Effect of Two-Step Versus Extended Infusions on the Pharmacokinetics of Imipenem in Patients with Sepsis and Septic Shock. Adv Ther. 2020 May;37(5):2246-2255. doi: 10.1007/s12325-020-01339-5. Epub 2020 Apr 10.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): November 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimate): November 26, 2015

Study Record Updates

• Last Update Posted (Estimate): November 26, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; pharmacodynamic; imipenem; sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Anti-Infective Agents; Anti-Bacterial Agents; Imipenem
• Other Study ID Numbers: Two-step Dosing Of Imipenem