Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation

NCT05542446 | Terminated Phase 4

• 2 other identifiers: COL-ECMO20222022-000291-19
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Colistin

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 hours

Secondary Outcomes (5)

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

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

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

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

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

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

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

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

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

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

Study Arms (2)

Critically ill patients with ECMO

EXPERIMENTAL

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.

Drug: Colistin

Critically ill patients without ECMO

ACTIVE COMPARATOR

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.

Drug: Colistin

Interventions

Colistin DRUG

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.

Also known as: colistin methanesulfonate, colistimethate

Critically ill patients with ECMO; Critically ill patients without ECMO

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• St. Anne's University Hospital Brno, Czech Republic: lead
• Palacky University: collaborator

Study Sites (1)

St. Anne's University Hospital Brno

Brno, Czech Republic, 60200, Czechia

Location

Related Publications (1)

• Suk P, Rychlickova J, Souckova L, Kubickova V, Urbanek K. Changes of colistin pharmacokinetics in critically ill patients due to the extracorporeal membrane oxygenation: protocol for the COL-ECMO2022 trial - a prospective, non-randomised, open-label phase IV pharmacokinetic clinical trial. BMJ Open. 2023 Jul 30;13(7):e071649. doi: 10.1136/bmjopen-2023-071649.

  PMID: 37518089 DERIVED

MeSH Terms

Conditions

Critical Illness

Interventions

Colistin; colistinmethanesulfonic acid

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Officials

• Lucie Tesárková, Scs.

  St. Anne´s University Hospital Brno

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: September 15, 2022
• Study Start: September 1, 2022
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)