Colistin Pharmacokinetics in Critically Ill Patients During Extended Dialysis

Colistin Pharmacokinetics in Critically Ill Patients With Acute Kidney Injury AKIN III During Extended Dialysis Using the GENIUS Dialysis System

The emergence of multidrug-resistant bacteria has recently renewed interest in colistin. Data on dosing in critically ill patients undergoing extended dialysis are missing. The aim of this study is to determine the pharmacokinetics of colistin during extended dialysis in critically ill patients and to provide dosing guidelines for this drug.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Infection Due to Resistant Bacteria

Detailed Description

Due to the lack of new antibiotics for the treatment of critically ill patients with multidrug-resistant bacteria, interest in "old" antibiotics like colistin re-emerged. Lastly, colistin is administered more frequently especially in cases of infections due to Pseudomonas aeruginosa, Klebsiella pneumoniae or Acinetobacter baumanii in intensive care units (ICUs) around the world. However, dosing of colistin in critically ill patients undergoing renal replacement therapy is based on scarce data. The aim of this study is to evaluate single and multiple-dose pharmacokinetics of both colistin and its inactive prodrug colistin-methanesulfonate (CMS) in critically ill patients with acute kidney injury (AKI) undergoing extended daily dialysis (EDD).

The investigators perform a prospective clinical pharmacokinetic single- and multiple-dose study in the medical and surgical ICUs of the Hannover Medical School. ICU patients with anuric AKI being treated with EDD and receiving i.v. colistin are studied on day 1 and (if possible) on day 5-9 of treatment. A loading dose of 6 Mio IU colistin ís administered 8 hours prior to the EDD session followed by 3 Mio IU every 8 hours. Colistin Plasma concentration levels as well as dialyzer clearance rates are measured at different time points.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Critically ill patients in a tertiary hospital with acute kidney injury AKIN III with need for renal replacement and colistin therapy.

Description

Inclusion Criteria:

• Indication for colistin therapy
• Acute kidney injury AKIN III with need for renal replacement therapy

Exclusion Criteria:

• participation in other studies
• pregnancy
• known colistin allergy or other contraindications for colistin therapy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colistin elimination during extended dialysis	Colistin elimination during extended dialysis is measured on day 1 and day 9 after colistin therapy was started. Colistin elimination is measured by the total eliminated drug amount in the total spent dialysate	Participants will be followed for 10 days. Colistin elimination measured by the total drug amount in the collected spent dialysate

Secondary Outcome Measures

Outcome Measure	Time Frame
Colistin peak concentration during extended daily dialysis C(max)	Participants will be followed for 10 days. Colistin concentration is measured at different time points after drug infusion: 0, 0.5, 1, 1.5, 2, 4, 6, 8) on day 1 and day 9 after therapy initiation
Colistin trough Level during extended daily dialysis C(max)	Participants will be followed for 10 days. Colistin concentration is measured at different time points after drug infusion: 0, 0.5, 1, 1.5, 2, 4, 6, 8) on day 1 and day 9 after therapy initiation
Colistin dialyzer clearance during extended dialysis	Participants will be followed for 10 days. Dialyzer clearance is calculated after 30 and 180 minutes of extended dialysis on day 1 and day 9 after therapy initiation

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Jan T Kielstein, Prof, Hannover Medical School, Dep. of Nephrology and Hypertension

Publications and helpful links

General Publications

• Schmidt JJ, Strunk AK, David S, Bode-Boger SM, Martens-Lobenhoffer J, Knitsch W, Scherneck S, Welte T, Kielstein JT. Single- and multiple-dose pharmacokinetics and total removal of colistin in critically ill patients with acute kidney injury undergoing prolonged intermittent renal replacement therapy. J Antimicrob Chemother. 2019 Apr 1;74(4):997-1002. doi: 10.1093/jac/dky511.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: August 24, 2015
• First Submitted That Met QC Criteria: September 18, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Estimate): August 24, 2016
• Last Update Submitted That Met QC Criteria: August 23, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: COL-6446-2013