Blend to Limit Oxygen in ECMO: A Randomised Controlled Registry Trial (BLENDER)

Blend to Limit oxygEN in ECMO: a ranDomised controllEd Registry Trial The BLENDER Trial - A Phase II Multicentre Randomised Controlled Trial

To determine in patients requiring venoarterial (V-A) ECMO, whether the use of a conservative as compared with liberal oxygen strategy, results in a greater number of ICU-free days at day 28.

Study Overview

• Status: Active, not recruiting
• Conditions: Critical Illness; Cardiac Failure
• Intervention / Treatment: Drug: Oxygen

Detailed Description

Extracorporeal membrane oxygenation (ECMO) can be a lifesaving procedure for the sickest patients in the Intensive Care Unit (ICU) who are at risk of death from severe cardiac and respiratory failure. ECMO is a device which pumps blood out of the body and returns it back after adding oxygen and removing carbon dioxide. While potentially life-saving, ECMO is associated with high use of critical care resources and increased risk of adverse outcomes in survivors.

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. Both strategies are currently standard practice worldwide, however, there is no consensus to which strategy is better for our patients. This trial aims to utilise an existing intensive care registry and will recruit 300 patients with life threatening acute cardiac or respiratory failure. If the BLENDER Trial confirms that one oxygen management strategy is more effective than the other, its findings may improve the lives of critically ill Australians and inform clinical practice worldwide.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kelly Ottosen; Phone Number: (03) 99030034; Email: kelly.ottosen@monash.edu

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥18 years who are commenced on V-A ECMO for severe cardiac, or following refractory cardiac arrest.

Exclusion Criteria:

• Greater than 6 hours have elapsed from the time of initiation of ECMO to randomisation
• Patients who are suspected or confirmed to be pregnant
• Where an indication exists for a specific oxygen target as part of clinical care (e.g. carbon monoxide poisoning)
• Patients who are already enrolled in another oxygen titration study (unless agreed by study committees)
• Patients not willing to receive blood products (e.g. Jehovah's Witness)
• Where the treating physician deems the study is not in the patient's best interest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conservative Oxygen Management Strategy; Patients allocated to the conservative strategy will have the ECMO blender oxygen fraction (FbO2) will be titrated to achieve a post-oxygenator saturations of 92-96% (the FbO2 cannot be reduced to lower than 0.5). Post-oxygenator arterial blood gases (ABG's) will be taken to ensure safety and to allow for adjustments to be made. The ventilator FiO2 will be titrated to patient oxygen saturations (SpO2) of 92-96%.	Drug: Oxygen; Conservative oxygen management strategy- reduces oxygen on the inoblender in the ECMO circuit. Liberal oxygen management strategy - does not reduce the oxygen on the inoblender via the ECMO circuit
Active Comparator: Liberal Oxygen Management Strategy; Patients allocated to the liberal strategy will have the FbO2 set at 1.0 at all times. The ventilator FiO2 will be titrated to achieve a patient oxygen saturations (SpO2) of 97-100% (but not lower than 0.5).	Drug: Oxygen; Conservative oxygen management strategy- reduces oxygen on the inoblender in the ECMO circuit. Liberal oxygen management strategy - does not reduce the oxygen on the inoblender via the ECMO circuit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome will be the number of alive and ICU-free days to day 28.	ICU free days are defined as the total number of days (or part days) being free of ICU between randomisation and day 28, with the exception that all patients who die by day 28 will be defined as having zero ICU free days.	at day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disability	World Health Organisation's Disability Assessment Schedule 2.0 12L	6 and 12 months
Health-related quality of life at six and twelve months using the EQ5D-5L	Euro Qol Group Health Survey (EQ-5D-5L) Measuring quality of life which looks at five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.	6 and 12 months
Psychological function at six and twelve months	Measured using a trained, blinded assessor via telephone interview	6 months & 12 months
Hospital mortality	Mortality rates of patients that day in hospital from randomisation to day 28	at day 28
ICU mortality	Mortality rates of patients that day in ICU from randomisation to day 28	at day 28
ICU length of stay	Number of hours spent in ICU from randomisation up to day 28	at day 28
Duration of mechanical ventilation	Number of hours requiring mechanical ventilation from randomisation to day 28	at day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECMO circuit life	number of hours that each circuit was in use	day 28

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Investigators: Principal Investigator: David Pilcher, Monash University, Australian & New Zealand Intensive Care research Centre

Publications and helpful links

General Publications

• Joyce CJ, Anderson C, Shekar K. Hyperoxia on Venoarterial Extracorporeal Membrane Oxygenation: A Modifiable Risk? Crit Care Med. 2022 Jan 1;50(1):e99-e100. doi: 10.1097/CCM.0000000000005252. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2019
• Primary Completion (Actual): July 3, 2023
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: February 4, 2019
• First Submitted That Met QC Criteria: February 13, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: 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: ANZIC-RC/DP001

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