Optimization Dose Study on Pharmacokinetics and Pharmacodynamics of Colistin in Critically Ill Patients

Study Overview
=================
Brief Summary
-----------------
Phase II clinical trial, open-labelled, prospective and single-center study directed to obtain blood samples in experimental detailed conditions in order to compare and optimize the dose of colistin in critically ill patients suffering from infections on which the indication of colistin would be accepted according to normal local protocols for severe infections treatment.

Official Title
-----------------
Pharmacokinetics and Pharmacodynamics of Colistin in Critically Ill Patients With Severe Infections for Dose Optimization Study

Conditions
-----------------
Critical Illness

Intervention / Treatment
-----------------
* Drug: Colistin 6 million units + 240mg/8h
* Drug: Colistin 6 million units + 360mg/12h


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: More than 60 Kg of weigh Patients with directed treatment with colistin as the recommended antimicrobial treatment protocols in the hospital to treat some of the following serious infections caused by carbapenems resistant A. baumannii: (i) bacteremia; (ii) nosocomial pneumonia or (iii) infection of skin and soft tissue (cellulitis, abscesses or infected ulcers). Written informed consent form. Exclusion Criteria: Refractory shock or other illness with an expectative of life ˂ 48 hours after the recruitment; Patient declared not to resuscitation maneuvers; Suspicion or demonstration of endocarditis, osteomyelitis, or meningitis; Known hypersensitivity to polymyxins; Pregnancy.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colistin 6 million units + 240mg/8h<br>Loading dose of 6 million units of colistin+ 240mg/8h maintenance | Drug: Colistin 6 million units + 240mg/8h<br>* 240 mg of colistin methanesulfonate (CMS) every 8 hours, 3 million units (MU); 90 mg colistin base activity, (CBA)<br>* Other names: colistin base activity (CBA);|
| Experimental: Colistin 6 million units + 360mg/12h<br>Loading dose of 6 million units of colistin+ 360mg/12h maintenance | Drug: Colistin 6 million units + 360mg/12h<br>* 360 mg CMS every 12 hours (4.5 MU; 135 mg CBA)<br>* Other names: colistin base activity (CBA);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile; Cmax (maximum reach concentration)/ MIC( Minimum inhibitory concentration) >10 | Plasma concentration will be measured for pharmacokinetic and pharmacodynamic profile the samples were drawn at 60, 120, 180, 240, 360, and 480 min after the end of the loading dose infusion and in patients of the group B, two more samples are taken at 600 and 720 min after the loading dose. Main pharmacokinetic parameters will be Cmax (maximum reach concentration)/ MIC(Minimum inhibitory concentration)>10 | Day 1 and day 3 after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of drug adverse reactions | All study drug related adverse reactions will be gathered and communicated. | 21 days of follow-up | 
| Pharmacodynamic profile (Monte-Carlo simulation (statistical methodology) with MIC (Minimum inhibitory concentration) 50 y MIC (Minimum inhibitory concentration) 90 from samples isolation) | Monte-Carlo simulation (statistical methodology) with MIC (Minimum inhibitory concentration) 50 y MIC (Minimum inhibitory concentration) 90 from samples isolation | Day 1 and day 3 after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
infections, Skin infections, multidrug resistant Gram negative bacteria (MDR-GNB), Pneumonia, Bacteriemia, Nosocomial infections