Clinical trial NCT04674657: Does Extra-Corporeal Membrane Oxygenation Alter Antiinfectives Therapy Pharmacokinetics in Critically Ill Patients
Official title: Does Extra-Corporeal Membrane Oxygenation Alter Anti-infectives Therapy Pharmacokinetics in Adult Critically Ill Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Critical Illness
Extracorporeal Membrane Oxygenation Complication
Infection
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
First posted: 2020-12-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Critically ill patients on Extra-Corporeal Membrane Oxygenation

Brief summary: Observational study Primary Objective: To study whether ECMO alters the PK of anti-infectives including voriconazole, posaconazole and caspofungin in critically ill patients on ECMO

Secondary Objectives:

Develop Population PK models of anti-infectives, including voriconazole, posaconazole and caspofungin in critically ill patients on ECMO

Develop Physiological-Based PK (PBPK) model of anti-infectives, including: voriconazole, posaconazole and caspofungin in critically ill patients on ECMO

Study population: Critically ill patients on ECMO

Methodology: Observational study to determine whether ECMO alters the PK of anti-infectives, by developing PK models

This is a non-interventional descriptive study in that the anti-infective drug selection and dosing will be at the discretion of the clinician, based on the clinical context and unit guidelines. Doses will be reconstituted and administered as per local hospital protocols in line with patient's routine care. Patients will be asked to provide additional blood samples over the course of the anti-infective dosing schedule, these samples will be taken from existing arterial lines to help guide treatment in future patients on ECMO receiving these anti-infectives.

Detailed description: Anti-infective drug selection and dosing will be at the discretion of the clinician, based on the clinical context and unit guidelines. Doses will be reconstituted and administered as per local hospital protocols and based on routine standard care.

Blood samples will be drawn from an existing arterial line and collected in 3 ml tubes with Lithium Heparin anticoagulant.

All patients will be sampled over a single dosing period on the second day of Extra-Corporeal Membrane Oxygenation (ECMO) treatment, or of an antibiotic course where antibiotics are commenced whilst the patient is on ECMO. Where possible, sampling during one extra dosing interval will occur on days 4-8 of ECMO treatment and/or prior to the next tubing change. Where two or more anti-infectives of interest are prescribed for one patient, collect data on timing of administration for both drugs and sample according to the antibiotic with the longer dosing interval.

Blood samples (2ml) will be collected from an existing arterial line at the following time points 0 (pre-starting infusion, pre-Nasogastric (NG)/Oral (PO) dose), 1 (end of infusion or 1hour post NG/PO dose), 2, 3, 4, 8 and either 12 (for twice daily regimen) or 24 (for once daily regimen) hours on the second day of ECMO.

Where a patient is receiving medications where a validated drug assay exists in addition to the study drug (such as other anti-infectives), analysis of the additional therapy will also be attempted where practical.

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years and \<90 years
2. Currently undergoing ECMO for respiratory +/- cardiac dysfunction
3. Clinical indication for the anti-infectives, including voriconazole, posaconazole and caspofungin

Exclusion Criteria:

1. History of allergy to any of the study drug
2. Pregnant women

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of Caspofungin in adult critically ill patients on ECMO
timeFrame: 24 hour
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of Posaconazole in adult critically ill patients on ECMO
timeFrame: 24 hour
Secondary outcomes:
Other outcomes:
Locations:
city: Harefield
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
state: Middlesex
Study officials:
affiliation: Royal Brompton and Harefield NHS Foundation Trust
name: Anna Reed
role: PRINCIPAL_INVESTIGATOR
References: