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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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 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) 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. 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

Official Title
-----------------
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

Conditions
-----------------
ICU Patients

Intervention / Treatment
-----------------
* Diagnostic Test: kidney function assessment by 4 hour creatinine clearance
* Diagnostic Test: kidney function assessment by creatinine based eGFR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged over 18 Patients in intensive care unit received colistin for the microbiologically documented cases associated with carbapenem-resistant gram negative bacilli. Exclusion Criteria: Patients who received colistin empirically. Patients who received renal replacement therapy due to acute kidney injury or end-stage renal disease Patients whose urine output was less than 0.5cc/kg/hr for 6 hrs Patients who underwent hematopoietic stem cell transplantation Patients who disagree with this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind randomized trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>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<br>* creatinine based eGFR (which is not revised value with standardized body surface area, that is, 1.73m2) are used to decide colistin maintenance dosage.<br>|
| Experimental: Study group<br>4 hour creatinine clearance is used to decide colistin maintenance dosage. | Diagnostic Test: kidney function assessment by 4 hour creatinine clearance<br>* 4 hour creatinine clearance is used to decide colistin maintenance dosage.<br>|

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 | Measure Description | 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
drug dosing, eGFR, CCr