Does Extra-Corporeal Membrane Oxygenation Alter Antiinfectives Therapy Pharmacokinetics in Critically Ill Patients

Critical Illness Clinical Trial

— EAT-PK  

Official title:

Does Extra-Corporeal Membrane Oxygenation Alter Anti-infectives Therapy Pharmacokinetics in Adult Critically Ill Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04674657
• Other study ID #: 18/LO/0691
• Status: Recruiting
• Start date: September 3, 2018
• Est. completion date: September 2021

Study information

• Verified date: December 2020
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: Ms H Lyster
• Phone: 01895823737
• Email: h.lyster[@]rbht.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Extracorporeal Membrane Oxygenation Complication
• Infection

Intervention

Drug:
• blood drug concentration
blood drug concentration

Locations

Country	Name	City	State
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	Harefield	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration Versus Time Curve (AUC) of Caspofungin in adult critically ill patients on ECMO	Blood samples (2ml) will be collected from an existing arterial line at the following time points 0 (pre-starting infusion, pre-NG/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	24 hour
Primary	Area Under the Plasma Concentration Versus Time Curve (AUC) of Posaconazole in adult critically ill patients on ECMO	Blood samples (2ml) will be collected from an existing arterial line at the following time points 0 (pre-starting infusion, pre-NG/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	24 hour