Assessment of Kidney Function for Drug Dosage Adjustments in Critically Ill Patients

Overview

The aim of the study is to determine if colistin dosage adjustment using 4hr CrCl contribute to better clinical outcomes compared with drug dosage adjustment using eGFR in critical ill patients. In control group, colistin maintenance dosage will be decided using serum creatinine based eGFR (in ml/min). In study group, colistin maintenance dosage will be decided using 4hr CrCl.

Full Title of Study: “Reliable Methods to Assess Kidney Function for Drug Dosage Adjustments in Critically Ill Patients – Comparison of Timed Clearance of Creatinine and Creatinine Based Estimated GFR”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Outcomes Assessor)
  • Study Primary Completion Date: February 28, 2019

Detailed Description

1. Screening periods (From 'informed consents' to 'randomization') – Check of inclusion/exclusion criteria ② Measurement of 4hr CrCl & eGFR in ml/min – calculation of maintenance dose ③ Baseline characteristics & laboratory findings ④ Randomization 2. Colistin dosage Loading dose : 5 x body weight (not exceeding 300mg) Maintenance dose (after 12 hours from loading dose) : 2.5 x ([1.5 x GFR] + 30) (divided doses every 12hours), GFR in ml/min During the study period, daily morning serm creatinine levels are measured. Whenever serum creatinine concentration changes by more than 10% compared with baseline, 4hr CrCl will be mearued. At the every time of 4hr CrCl measurements, colistin dose wil be modified according to new GFR values (4hr CrCl in study group, eGFR in control group) 3. Blood sampling for Colistin trough level measurement Peripheral blood will be sampled twice between 72 hrs and 144 hours after loading dose, just before colistin infusion. The samples were collected in heparined tubes and centrifuged at 4 °C within 1 hr of collection. The resulting plasma was stored at – 70°C . And two values will be averaged out. 4. End of randomization (7 days after colistin initiation) ① Nephrotoxicity ② Treatment outcome microbiological outcome: eradication / no eradication clinical outcome: complete response / partial response / treatment failure

Interventions

  • Diagnostic Test: kidney function assessment by 4 hour creatinine clearance
    • 4 hour creatinine clearance is used to decide colistin maintenance dosage.
  • Diagnostic Test: kidney function assessment by creatinine based eGFR
    • creatinine based eGFR (which is not revised value with standardized body surface area, that is, 1.73m2) are used to decide colistin maintenance dosage.

Arms, Groups and Cohorts

  • Active Comparator: Control group
    • creatinine based eGFR (which is not revised value with standardized body surface area, that is, 1.73m2) are used to decide colistin maintenance dosage.
  • Experimental: Study group
    • 4 hour creatinine clearance is used to decide colistin maintenance dosage.

Clinical Trial Outcome Measures

Primary Measures

  • composite outcome (combination of nephrotoxicity or treatment failure)
    • Time Frame: 7 days after colistin initiation
    • Nephrotoxicity means development of AKI (according to RIFLE criterior) Treatment failure menas clinically ‘no response’

Secondary Measures

  • colistin trough level, renal clearance of colistin
    • Time Frame: 7 days after colistin initiation
  • ICU stay duration
    • Time Frame: till discharge (Max. 3 months)
  • Total duration of colistin treatment
    • Time Frame: till discharge (Max. 3 months)
  • Need for renal replacement therapy
    • Time Frame: 7 days after colistin initiation
  • In-ICU mortality (infection-attributed mortality)
    • Time Frame: till discharge (Max. 3 months)

Participating in This Clinical Trial

Inclusion Criteria

1. Patients aged over 18 2. Patients in intensive care unit received colistin for the microbiologically documented cases associated with carbapenem-resistant gram negative bacilli. Exclusion Criteria:

1. Patients who received colistin empirically. 2. Patients who received renal replacement therapy due to acute kidney injury or end-stage renal disease 3. Patients whose urine output was less than 0.5cc/kg/hr for 6 hrs 4. Patients who underwent hematopoietic stem cell transplantation 5. Patients who disagree with this study.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Samsung Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jung Eun Lee, Associate professor – Samsung Medical Center
  • Overall Contact(s)
    • Jung Eun Lee, MD,PhD, 82-2-3410-6549, jungeun34.lee@samsung.com

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