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

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

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.

Study Overview

• Status: Unknown
• Conditions: ICU Patients
• Intervention / Treatment: Diagnostic test: kidney function assessment by creatinine based eGFR; Diagnostic test: kidney function assessment by 4 hour creatinine clearance

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

• Study Type: Interventional
• Enrollment (Anticipated): 172
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
Experimental: Study group; 4 hour creatinine clearance is used to decide colistin maintenance dosage.	Diagnostic test: kidney function assessment by 4 hour creatinine clearance; 4 hour creatinine clearance is used to decide colistin maintenance dosage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite outcome (combination of nephrotoxicity or treatment failure)	Nephrotoxicity means development of AKI (according to RIFLE criterior) Treatment failure menas clinically 'no response'	7 days after colistin initiation

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): February 13, 2017
• Primary Completion (Anticipated): February 28, 2019
• Study Completion (Anticipated): April 30, 2019

Study Registration Dates

• First Submitted: February 5, 2017
• First Submitted That Met QC Criteria: February 5, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Estimate): February 8, 2017
• Last Update Submitted That Met QC Criteria: February 6, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: drug dosing, eGFR, CCr
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 2016-12-147-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No