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

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

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.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Drug: Colistin 6 million units + 240mg/8h; Drug: Colistin 6 million units + 360mg/12h

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: M. Eugenia Pachón, BD-PhD, Instituto de Biomedicina de Sevilla (IBiS); Study Chair: José Miguel Cisneros, MD-PhD, Hospitales Universitarios Virgen del Rocío

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Estimate): February 3, 2016
• Last Update Submitted That Met QC Criteria: February 2, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Pneumonia; infections; Bacteriemia; Nosocomial infections; multidrug resistant Gram negative bacteria (MDR-GNB); Skin infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Anti-Infective Agents; Anti-Bacterial Agents; Colistin
• Other Study ID Numbers: MagicBullet/COLPHAR

Plan for Individual participant data (IPD)

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