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

St. Anne's University Hospital Brno, Czech Republic

Status and phase: Terminated; Phase 4

Conditions: Colistin

Treatments: Drug: Colistin

Study type: Interventional

Funder types: Other

Identifiers

NCT05542446

2022-000291-19 (EudraCT Number)

COL-ECMO2022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No 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).

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Critically ill patients with ECMO

Experimental group

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.

Treatment:

Drug: Colistin

Critically ill patients without ECMO

Active Comparator group

Description:

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.

Treatment:

Drug: Colistin