PK Analysis of Piperacillin in Septic Shock Patients

NCT02306928 | Completed Results

• 1 other identifier: PIP/TAZO-ICU
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic changes seen in this population. Piperacillin/tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. We determined the pharmacokinetic profile of piperacillin 4g every 8 hour in 15 patients treated empirically for septic shock. A PK population model was established with the dual purpose to assess current standard treatment and to simulate alternative dosing regimens and modes of administration. Time above the minimal inhibitory concentration (T\>MIC) predicted for each patient were evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f T\>MIC and 50% fT\>4xMIC.

Conditions

Septic Shock

Keywords

Septic shock; Intensive care unit; Therapeutic drug monitoring; Pharmacokinetics; Critically ill

Outcome Measures

Primary Outcomes (2)

• 100% f T>MIC: Free Piperacillin Concentration Maintained Above the MIC Throughout the Dosing Interval.

  The piperacillin plasma concentration-time profiles were best described by a two-compartment model. Each individual model predicted T\>MIC was compared to clinical breakpoint MIC for P.aeruginosa (16 mg/L). The number of patients who achieved the pre-defined PK/PD target were reported.

  Participants were followed up to the third dosing interval after initiation of piperacillin/tazobactam. An average of 24 hours.

• 50% fT>4xMIC: Free Piperacillin Concentration Maintained at a Level Fourfold the MIC for at Least 50% of the Dosing Interval.

  The piperacillin plasma concentration-time profiles were best described by a two-compartment model. Each individual model predicted T\>MIC was compared to clinical breakpoint MIC for P.aeruginosa (16 mg/L). The number of patients who achieved the pre-defined PK/PD target were reported.

  Participants were followed up to the third dosing interval after initiation of piperacillin/tazobactam. An average of 24 hours.

Secondary Outcomes (3)

• The Maximum Concentration of Piperacillin (Cmax)

  Participants were followed up to the third dosing interval after initiation of piperacillin/tazobactam. An average of 24 hours.

• The Area Under the Plasma-concentration Time Curve Concentration-time Curve From 0-8 Hours After the Studied Dose (AUC 0-8)

  Participants were followed up to the third dosing interval after initiation of piperacillin/tazobactam. An average of 24 hours.

• Trough Piperacillin Plasma Concentration (Cmin)

  Participants were followed up to the third dosing interval after initiation of piperacillin/tazobactam. An average of 24 hours.

Study Arms (1)

Piperacillin pharmacokinetics

Patients with suspected septic shock who are treated with piperacillin/tazobactam.

Other: Blood draw

Interventions

Blood draw OTHER

Piperacillin pharmacokinetics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Critically ill patients with known or suspected septic shock admitted to the ICU, treated with piperacillin/tazobactam.

You may qualify if:

• Treatment with piperacillin/tazobactam for less than 24 hours. Treatment with noradrenaline. -

You may not qualify if:

• Renal replacement therapy. Age under 18.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of anesthesiology and intensive care, Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Related Publications (1)

• Obrink-Hansen K, Juul RV, Storgaard M, Thomsen MK, Hardlei TF, Brock B, Kreilgaard M, Gjedsted J. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations? Antimicrob Agents Chemother. 2015 Nov;59(11):7018-26. doi: 10.1128/AAC.01347-15. Epub 2015 Sep 8.

  PMID: 26349823 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood

MeSH Terms

Conditions

Shock, Septic; Critical Illness

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Disease Attributes

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Kristina Öbrink-Hansen
• Organization: Aarhus University Hospital, Department of infectious diseases

krisoebr@rm.dk

+45 7845 2845

Study Officials

• Merete Storgaard, MD

  Department of Infectious Diseases, Aarhus University Hospital, Denmark

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 3, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: February 11, 2016
• Results First Posted: June 11, 2015

Record last verified: 2016-02

Locations

DK (1)