RECOMMEND Platform Trial

Australian and New Zealand Intensive Care Research Centre

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Extracorporeal Membrane Oxygenation Complication

Treatments: Other: Liberal Transfusion; Other: Restrictive Transfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT06526533

ANZIC-RC/CH006

Details and patient eligibility

About

Patients in the intensive care unit (ICU) undergoing extracorporeal membrane oxygenation (ECMO) require close monitoring and interventions to support their recovery. The RECOMMEND Platform Trial aims to develop clear, high-quality evidence for ECMO care, to better inform clinicians in this rapidly evolving field.

The RECOMMEND Platform Trial will provide a 'platform' for funding, logistics, and training protocols. This approach enhances efficiency, allowing research to begin, and complete more efficiently. The platform maintains rigorous standards and provides a safe, cost-effective, and time-efficient method for generating knowledge about ECMO care.

Overall, platform clinical trials offer a dynamic and innovative approach that enables the simultaneous evaluation of multiple treatments and the rapid translation of scientific discoveries into improved patient care. The RECOMMEND Platform Trial has been informed by patient preferences and values and will evaluate the effectiveness and safety of various standards of care. This approach supports continuous learning and real-time clinical decision-making to improve patient outcomes.

Full description

The RECOMMEND Platform trial is an investigator initiated, multicentre, open labelled, randomised controlled Platform Trial that will utilise Bayesian adaptive logic to investigate the efficacy and safety of multiple study interventions simultaneously or sequentially in cohorts of adult patients who are receiving ECMO from ICUs participating in the national ECMO registry (EXCEL) in Australian and New Zealand ICU hospitals.

In this platform trial, various interventions within the scope of standard care will be investigated for their potential to improve outcomes for patients undergoing ECMO. Standard care will be used as the common control arm for all intervention cohorts.

Extracorporeal Membrane Oxygenation (ECMO) is an invasive and resource intensive treatment used to support critically ill patients suffering from severe cardiac arrest, cardiac failure or respiratory failure. ECMO provides mechanical circulatory support, temporarily replacing the function of the heart and/or lungs, allowing time for these organs to recover.

Globally, the use of ECMO has increased rapidly over the past decade. It is both invasive and expensive, with the average cost for a single admission in Australia exceeding more than $180,000 and a total annual cost of > $75 million. Despite its high cost, ECMO is associated with a high mortality rate, and many survivors have compromised functional recovery for months or years after discharge from hospital, further adding to the long-terms costs of care.

The main complications reported in the national ECMO registry from 2019-2022 include bleeding (51.4%), renal failure and fluid overload (78.4%), and death and ongoing disability (66%). These were confirmed as research priorities by consumers and end-users. While the use of ECMO increases swiftly, the evidence base to support the growing patient numbers receiving this care has not grown at the same rate, resulting in important evidence gaps.

The RECOMMEND Platform Trial will address these evidence gaps in ECMO services in Australia. A platform trial is a type of study design that evaluates multiple treatment interventions for a single condition or device simultaneously within a single, overarching framework. This framework operates similarly to a standard operating procedure for study logistics, ethics management, funding, staffing, and statistical and data collection methods. Having an approved process (platform) for the 'Platform Trial' to operate saves time and money and increases speed of clinical trial onboarding to outcome resolution for researchers, hospital staff, ethics committees, and stakeholders. With this platform in place, future studies of similar ECMO outcomes can be onboarded more efficiently, as described above, and it creates a more powerful pool of data for impactful patient-centred research.

The aim of the RECOMMEND Platform Trial is to determine, in patients with acute cardiorespiratory failure requiring ECMO, the efficacy, safety and cost-effectiveness of a range of interventions.

Over the lifetime of RECOMMEND, it is anticipated that new interventions will be added as new domains. The creation of new domains will be considered according to priorities set by relevant working groups, based on existing or new clinical need and there being sufficient statistical power available within RECOMMEND.

Enrollment: 900 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

All patients enrolled in the EXCEL Registry (NCT03793257) who meet the inclusion and none of the exclusion criteria are eligible to participate.

Inclusion Criteria:

• Patients receiving ECMO
• Patients enrolled in the EXCEL Registry

Exclusion Criteria:

• Treating clinician regards death as imminent and inevitable
• Treating clinician determines it is not in the patient's best interests

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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900 participants in 2 patient groups

Blood Transfusion Domain: Red Blood Cell Transfusion in ECMO - Restrictive

Active Comparator group

Description:

This is a domain within the RECOMMEND Platform Trial to test the effectiveness of various blood transfusion strategies for patients with acute cardiorespiratory failure undergoing ECMO treatment in ICU. Arm details: The Australian Blood Authority's guidelines recommend a transfusion trigger of haemoglobin (Hb) levels between 70g/L and 90g/L for critically ill patients in ICU. However, this range is broad, and allows great variation in standard care. ROSETTA is a comparative effectiveness trial, assigning patients to two intervention groups that are in the realm of standard care. Participants are patients receiving extracorporeal membrane oxygenation (ECMO) in ICU who are eligible for inclusion in the EXCEL National ECMO Registry. Trigger: If a patient's Hb concentration reads ≤ 70g/L, one unit of RBC will be transfused. Additional units can be prescribed if required to raise the Hb concentration to above 70g/L.

Treatment:

Other: Restrictive Transfusion

Blood Transfusion Domain: Red Blood Cell Transfusion in ECMO - Liberal

Active Comparator group

Description:

This is a domain within the RECOMMEND Platform Trial to test the effectiveness of various blood transfusion strategies for patients with acute cardiorespiratory failure undergoing ECMO treatment in ICU. Arm details: The Australian Blood Authority's guidelines recommend a transfusion trigger of haemoglobin (Hb) levels between 70g/L and 90g/L for critically ill patients in ICU. However, this range is broad, and allows great variation in standard care. ROSETTA is a comparative effectiveness trial, assigning patients to two intervention groups that are in the realm of standard care. Participants are patients receiving extracorporeal membrane oxygenation (ECMO) in ICU who are eligible for inclusion in the EXCEL National ECMO Registry. Trigger: If a patient's Hb concentration reads ≤ 90g/L, one or more units of RBC will be transfused. Additional units can be prescribed to raise the Hb concentration to greater than 90g/L

Treatment:

Other: Liberal Transfusion