Clinical trial

Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation

Name

COL-ECMO2022

Description

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.

Trial arms

Trial start

2022-09-01

Estimated PCD

2024-01-19

Trial end

2024-01-19

Status

Terminated

Phase

Early phase I

Treatment

Colistin

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.

Arms:

Critically ill patients with ECMO, Critically ill patients without ECMO

Other names:

colistin methanesulfonate, colistimethate

Size

Primary endpoint

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

24 hours

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).

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 8, 'type': 'ACTUAL'}}

Updated at

2024-01-31

1 organization

1 product

1 indication

Organization

St. Anne's University Hospital Brno

Product

Colistin

Indication

Polymyxin E