Does Extra-Corporeal Membrane Oxygenation Alter Antiinfectives Therapy Pharmacokinetics in Critically Ill Patients (EAT-PK)

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

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.

Study Overview

• Status: Unknown
• Conditions: Critical Illness; Infection; Extracorporeal Membrane Oxygenation Complication
• Intervention / Treatment: Drug: blood drug concentration

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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Ms H Lyster; Phone Number: 85087 01895823737; Email: h.lyster@rbht.nhs.uk

Study Locations

• United Kingdom
  • Middlesex
    • Harefield, Middlesex, United Kingdom, UB9 6JH
      • Recruiting
      • Royal Brompton & Harefield NHS Foundation Trust
      • Contact: Haifa Lyster; Phone Number: 7850592073 7850592073; Email: h.lyster@rbht.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Critically ill patients on Extra-Corporeal Membrane Oxygenation

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
caspofungin; Adult critically ill patients on ECMO receiving caspofungin therapy	Drug: blood drug concentration; blood drug concentration
posaconazole; Adult critically ill patients on ECMO receiving posaconazole therapy	Drug: blood drug concentration; blood drug concentration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Investigators: Principal Investigator: Anna Reed, Royal Brompton and Harefield NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 18/LO/0691

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No