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

Study Overview
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Brief Summary
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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 60.

Detailed Description
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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.

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

Conditions
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Cardiac Failure, Critical Illness

Intervention / Treatment
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* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase II, registry-based, multicentre, parallel group randomised controlled trial. (Data retrieved from the EXCEL national clinical registry)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conservative Oxygen Management Strategy<br>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<br>* 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<br>|
| Active Comparator: Liberal Oxygen Management Strategy<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be the number of alive and ICU-free days at day 60. | ICU free days are defined as the total number of days (or part days) being free of ICU between randomisation and day 60, with the exception that all patients who die by day 60 will be defined as having zero ICU free days. | at day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital mortality | Mortality rates of patients that day in hospital from randomisation to day 60 | at day 60 | 
| ICU mortality | Mortality rates of patients that day in ICU from randomisation to day 60 | at day 60 | 
| ICU length of stay | Number of hours spent in ICU from randomisation up to day 60 | at day 60 | 
| Duration of mechanical ventilation | Number of hours requiring mechanical ventilation from randomisation to day 60 | at day 60 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, V-A ECMO, Oxygen, Hyperoxia