Clinical trial NCT05542446: Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation
Official title: Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Colistin
Keywords: colistin
critically ill
pharmacokinetics
extracorporeal membrane oxygenation
investigator-initiated study
Lead sponsor: St. Anne's University Hospital Brno, Czech Republic
Sponsor class: OTHER
Collaborators: name: Palacky University
First posted: 2022-09-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: OTHER

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.

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).

Primary outcomes:
measure: Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.
timeFrame: 24 hours
Secondary outcomes:
measure: Model of population pharmacokinetics of colistin in critically ill patients - Cmax
timeFrame: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
measure: Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc
timeFrame: 2 hours after colistin administration. The model will be designed through study completion, an average of 1 year
measure: Model of population pharmacokinetics of colistin in critically ill patients - Tminc
timeFrame: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
measure: Model of population pharmacokinetics of colistin in critically ill patients - Cmin
timeFrame: 12 hours after colistin administration. The model will be designed through study completion, an average of 1 year
measure: Model of population pharmacokinetics of colistin in critically ill patients - AUC
timeFrame: 24 hours after colistin administration. The model will be designed through study completion, an average of 1 year
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: St. Anne's University Hospital Brno
state: Czech Republic
Study officials:
affiliation: St. Anne´s University Hospital Brno
name: Lucie Tesárková, Scs.
role: STUDY_CHAIR
References: