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Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation (COL-ECMO2022)

Primary Purpose

Colistin

Status

Recruiting

Phase

Phase 4

Locations

Czechia

Study Type

Interventional

Intervention

Colistin

About this trial

This is an interventional other trial for Colistin focused on measuring colistin, critically ill, pharmacokinetics, extracorporeal membrane oxygenation, investigator-initiated study

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18 years
Men and women (with a negative pregnancy test prior to study enrolment in women of childbearing potential)
Hospitalized at the Department of Anaesthesiology and Resuscitation, St. Anne´s University Hospital Brno
Indication for parenteral colistin (or CMS) as part of standard medical care, i.e., in patients with severe bacterial infection
Informed consent given. In unconscious patients, the study investigator will decide whether to include the patient in the study; this decision is made whenever possible in a medical council consisting of at least one independent physician informed about the study details and one study investigator. An interim informed consent will be given after considering all individual risks. In this case, the Ethics Committee of St. Anne's Hospital in Brno will be informed of the patient's inclusion. The investigator will ask study participants in whom good quality consciousness is restored to give subsequent informed consent without unreasonable delay.

Additional inclusion criterion:

For some patients (15 individuals are expected), in addition to all the criteria listed in the Eligibility Criteria section, the following inclusion criterion is provided:

ECMO support is needed as part of standard therapy for severe respiratory failure.

Exclusion Criteria:

Pregnancy,
Breast-feeding,
Refusal to give the informed consent (primarily or after regaining consciousness).

Sites / Locations

St. Anne's University Hospital BrnoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Critically ill patients with ECMO

Critically ill patients without ECMO

Arm Description

The subjects connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours.

The subjects not connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours.

Outcomes

Primary Outcome Measures

Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.

The primary objective of the clinical trial is to determine the area under the plasma concentration versus time curve of colistin and CMS in critically ill patients with and without ECMO during the dosing interval, calculate and compare the area under the plasma concentration versus time curve of CMS and colistin in each group.

Secondary Outcome Measures

Model of population pharmacokinetics of colistin in critically ill patients - Cmax

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The first one is maximum plasma concentrations [Cmax] that will be obtain 2 hours after colistin administration.

Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The second one is time to maximum plasma concentration (Tmaxc) that will be calculated within 2 hours after colistin administration.

Model of population pharmacokinetics of colistin in critically ill patients - Tminc

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The third one is time to minimum plasma concentration (Tminc) that will be calculated within 12 hours after colistin administration.

Model of population pharmacokinetics of colistin in critically ill patients - Cmin

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fourth one is minimum plasma concentration (Cmin) that will be calculated within 12 hours after colistin administration.

Model of population pharmacokinetics of colistin in critically ill patients - AUC

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fifth one is Area Under the Curve (AUC) that will be calculated within 24 hours after colistin administration.

Full Information

NCT ID

NCT05542446

First Posted

August 18, 2022

Last Updated

December 27, 2022

Sponsor

St. Anne's University Hospital Brno, Czech Republic

Collaborators

Palacky University

1. Study Identification

Unique Protocol Identification Number

NCT05542446

Brief Title

Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation

Acronym

COL-ECMO2022

Official Title

Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2022 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Anne's University Hospital Brno, Czech Republic

Collaborators

Palacky University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Colistin is a lipopeptide antibiotic administered as an inactive prodrug - colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity dependent on plasma concentrations. The number of patients with these types of infections, as well as the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure, increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment.

Detailed Description

The COL-ECMO2022 study is a prospective, non-randomized, open-label single-center, phase IV clinical trial that is designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. The study is planned to include up to 30 patients with indication of colistin who will be assigned to one of two arms in a 1:1 ratio depending on the presence/absence of ECMO. All study participants will receive colistin standard, approved dose schedule intravenously. The plasma concentrations of colistin and CMS took at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals. Discussion: This study is expected to provide essential evidence-based data on the impact of ECMO on colistin pharmacokinetics in critically ill patients as well as to shed some light on how to optimize the colistin dosing for critically ill patients on ECMO by designing the population model.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colistin

Keywords

colistin, critically ill, pharmacokinetics, extracorporeal membrane oxygenation, investigator-initiated study

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

The primary objective of the clinical trial is to determine the plasma concentrations of colistin and CMS during the one or more monitored dosing interval(s) in critically ill patients with and without ECMO under the real clinical practice conditions; based on these data to calculate and compare the pharmacokinetic parameters (Cmax, Tmax, Ctrough, AUC, Vd, clearance) of CMS and colistin in each group.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Critically ill patients with ECMO

Arm Type

Experimental

Arm Description

Arm Title

Critically ill patients without ECMO

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Colistin

Other Intervention Name(s)

colistin methanesulfonate, colistimethate

Intervention Description

Visit 1 - screening - Patient selection phase. Patients meeting the eligibility criteria will be screened if not meeting any of the exclusion criteria. A pregnancy test from a urine test will be performed on women of childbearing potential. The patient will be offered participation in the clinical trial and interviewed by the investigator. Visit 2 (Visit 8, Visit 14 - optional, only if colistin is still indicated) - CMS administration The patient will be hospitalized at FNUSA. CMS will be given intravenously via the central vein catheter (a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours; only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours). Visit 3 - Visit 7 (Visit 9-Visit 13, Visit 15-Visit 19 - optional, only if colistin is still indicated) - Pharmacokinetics blood samples collection.

Primary Outcome Measure Information:

Title

Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.

Description

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Model of population pharmacokinetics of colistin in critically ill patients - Cmax

Description

Time Frame

2 hours after colistin administration. The model will be designed through study completion, an average of 1 year

Title

Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc

Description

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The second one is time to maximum plasma concentration (Tmaxc) that will be calculated within 2 hours after colistin administration.

Time Frame

2 hours after colistin administration. The model will be designed through study completion, an average of 1 year

Title

Model of population pharmacokinetics of colistin in critically ill patients - Tminc

Description

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The third one is time to minimum plasma concentration (Tminc) that will be calculated within 12 hours after colistin administration.

Time Frame

12 hours after colistin administration. The model will be designed through study completion, an average of 1 year

Title

Model of population pharmacokinetics of colistin in critically ill patients - Cmin

Description

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fourth one is minimum plasma concentration (Cmin) that will be calculated within 12 hours after colistin administration.

Time Frame

12 hours after colistin administration. The model will be designed through study completion, an average of 1 year

Title

Model of population pharmacokinetics of colistin in critically ill patients - AUC

Description

To propose a model of population pharmacokinetics of colistin in critically ill patients. The pharmacokinetic model will be designed as a composite of several pharmacokinetics parameters that will be obtained during the individual measurements. The fifth one is Area Under the Curve (AUC) that will be calculated within 24 hours after colistin administration.

Time Frame

24 hours after colistin administration. The model will be designed through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years Men and women (with a negative pregnancy test prior to study enrolment in women of childbearing potential) Hospitalized at the Department of Anaesthesiology and Resuscitation, St. Anne´s University Hospital Brno Indication for parenteral colistin (or CMS) as part of standard medical care, i.e., in patients with severe bacterial infection Informed consent given. In unconscious patients, the study investigator will decide whether to include the patient in the study; this decision is made whenever possible in a medical council consisting of at least one independent physician informed about the study details and one study investigator. An interim informed consent will be given after considering all individual risks. In this case, the Ethics Committee of St. Anne's Hospital in Brno will be informed of the patient's inclusion. The investigator will ask study participants in whom good quality consciousness is restored to give subsequent informed consent without unreasonable delay. Additional inclusion criterion: For some patients (15 individuals are expected), in addition to all the criteria listed in the Eligibility Criteria section, the following inclusion criterion is provided: ECMO support is needed as part of standard therapy for severe respiratory failure. Exclusion Criteria: Pregnancy, Breast-feeding, Refusal to give the informed consent (primarily or after regaining consciousness).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pavel Suk, Assoc. prof.

Phone

+420 543 183 537

pavel.suk@fnusa.cz

First Name & Middle Initial & Last Name or Official Title & Degree

Jitka Rychlíčková, Ph.D.

Phone

+420 549 49 6025

rychlickova@med.muni.cz

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lucie Tesárková, Scs.

Organizational Affiliation

St. Anne´s University Hospital Brno

Official's Role

Study Chair

Facility Information:

Facility Name

St. Anne's University Hospital Brno

City

Brno

State/Province

Czech Republic

ZIP/Postal Code

60200

Country

Czechia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pavel Suk, M.D., Ph.D., Assoc. Prof.

Phone

00420543183537

pavel.suk@fnusa.cz

First Name & Middle Initial & Last Name & Degree

Jitka Rychlickova, PharmDr. Ph.D.

Phone

00420543182175

jitka.rychlickova@fnusa.cz

First Name & Middle Initial & Last Name & Degree

Pavel Suk, M.D., Ph.D.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation

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