Blender Biomarkers: A BLENDER Sub-study to Evaluate the Effect of Oxygen Dose on Oxidative Stress and Organ Injury

To compare the impact of liberal vs conservative oxygen doses on markers of oxidative stress in patients enrolled in the BLENDER trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Critical Illness; Cardiac Failure

Detailed Description

Extracorporeal membrane oxygen (ECMO) is a heart lung support device used for patients with severe and cardiac and respiratory failure and carries an increased risk of exposure to very high oxygen tensions. Hyperoxia (arterial oxygen >100mmHg) can lead to the production of reactive oxygen species (ROS). Excess production of ROS and depletion of antioxidant compounds is referred to as oxidative stress and results in inflammation, tissue injury and cell death. The inter-relationship between the production of ROS and end organ dysfunction is complicated and remain unclear. A more detailed assessment of the timing of changes in markers of oxidative stress, inflammatory mediators and tissue injury is warranted to understand the processes and potentially identify therapeutic targets.

The BLENDER Trial is a multicentre trial in ECMO patients to determine whether a conservative oxygen strategy during ECMO reduces ICU length of stay and improves patient outcomes compared to a liberal oxygen strategy. Currently there have been no studies that look at the underlying pathophysiological changes that occur in patients on ECMO when subjected to different oxygen concentrations. As such The BLENDER study represents a unique opportunity to understand the mechanisms by which hyperoxia may cause tissue injury in patients receiving ECMO. This nested study seeks to elucidate whether exposure to hyperoxia during ECMO results in increased oxidative stress and whether this is correlated with increased risk of tissue injury and organ dysfunction. A better understanding of the mechanism of hyperoxia induced tissue injury may allow treatment to be optimised for patients exposed to hyperoxia as part of their treatment.

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

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

VA-ECMO patients enrolled in the BLENDER trial

Description

Inclusion Criteria:

• Patients receiving venoarterial (VA) ECMO
• Enrolled in the BLENDER trial

Exclusion Criteria:

• Not enrolled in the BLENDER trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Super oxide dismutase levels U/ml	Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO	Within 24 hours of ECMO commencement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marker of Cardiac Injury	Troponin ng/ml This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 3 of ECMO
Marker of Cardiac Injury	Troponin I ng/ml This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 7 of ECMO
Markers of Liver Injury	ALT and AST (IU/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 3 of ECMO
Markers of Liver Injury	ALT and AST (IU/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 7 of ECMO
Marker of Neurological Injury	Neuron Specific Enolase (microg/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 3 of ECMO
Marker of Neurological Injury	Neuron Specific Enolase (microg/L) This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 7 of ECMO
Coagulation Parameters	APTT This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 3 of ECMO
Coagulation Parameters	APTT This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 7 of ECMO
Immune Markers	IL-6, TNFa, IL-10, IL-1B (pg/ml)	Day 3 of ECMO
Immune Markers	IL-6, TNFa, IL-10, IL-1B (pg/ml)	Day 7 of ECMO
Other Markers of Oxidative Stress	Malondialdehyde, Vitamin C	Day 3 of ECMO
Other Markers of Oxidative Stress	Malondialdehyde, Vitamin C	Day 7 of ECMO
Superoxide dismutase levels U/ml	Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO	On Day 3 following ECMO commencement
Superoxide dismutase levels	Plasma levels of superoxide dismutase in patients exposed to either a liberal or conservative oxygen strategy during VA-ECMO	On Day 7 following ECMO commencement
Markers of Kidney Injury	Creatinine (micromol/L)	Day 3 of ECMO
Markers of Kidney Injury	Creatinine (micromol/L)	Day 7 of ECMO

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marker of Fibrinolysis	Fibrinogen, Plasmin anti-plasmin complex, D-Dimer This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 3 of ECMO
Marker of Fibrinolysis	Fibrinogen, Plasmin anti-plasmin complex, D-dimer This will be determined by analysing blood samples routinely collected daily from patient receiving ECMO	Day 7 of ECMO

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2022
• Primary Completion (Actual): August 3, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Oxidative stress; ECMO; Oxygen; V-A ECMO; Hyperoxia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Heart Failure; Critical Illness
• Other Study ID Numbers: HREC/50486/Alfred-2019

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