Clinical trial NCT06526533: RECOMMEND Platform Trial
Official title: Generating New Evidence to Reduce Major Complications to Improve the Safety and Efficacy of ECMO in Severe Cardiac and Respiratory Failure (RECOMMEND)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Extracorporeal Membrane Oxygenation Complication
ARDS (Acute Respiratory Distress Syndrome)
Intensive Care Medicine
Cardiac Arrest (CA)
Critical Illness
Keywords: ECMO
ICU
Platform Trial
Australia
Cardiac
Respiratory
VA
VV
eCPR
Adaptive
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: Monash University
name: Berry Consultants
name: Research Path
First posted: 2024-07-30
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this platform trial is to determine the efficacy, safety and cost-effectiveness of various interventions in patients with acute cardiorespiratory failure requiring extracorporeal membrane oxygenation (ECMO)

The main question the platform trial aims to address is to determine the effect of a range of interventions on survival, organ support and resource utilisation to day 28 for hospitalised patients receiving ECMO.

Researchers will compare various interventions within multiple platform trial domains to see if the interventions have effects on survival, organ support and resource utilisation for the patient cohort.

Participants will be enrolled in accordance with the platform trial's domain structure to answer the research questions.

Detailed 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 hospitals (EXCEL Registry NCT03793257).

In this platform trial, various interventions will be investigated for their potential to improve outcomes for patients undergoing ECMO.

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.

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.

Eligibility criteria: PLATFORM INCLUSION CRITERIA:

* Patients receiving ECMO
* Patients enrolled in the EXCEL Registry - NCT03793257

PLATFORM EXCLUSION CRITERIA:

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

RBC TRANSFUSION DOMAIN INCLUSION CRITERIA:

• Aged 18 years or older

RBC TRANSFUSION DOMAIN EXCLUSION CRITERIA:

* Contraindication to RBC transfusion (including known patient preference)
* Limitations of care put in place either through patient wishes or the treating medical teams.
* Participant has already received ECMO \>12 hours. The start of ECMO is defined as the time of initiation of extracorporeal blood flow unless ECMO was initiated during a surgical intervention in which case the start of ECMO is defined as the arrival time into the initial ICU (post-surgery)
* The treating physician anticipates that ECMO treatment will cease before the end of tomorrow
* The treating physician deems the study is not in the patient's best interest
* The treating physician has concern regarding patient ability to tolerate restrictive or liberal transfusion trigger thresholds
* Actively listed for a solid organ transplant and has not yet received one
* Suspected or confirmed to be pregnant
* Previous ECMO treatment during the same hospital admission

Primary outcomes:
measure: Daily Organ Support for patients on ECMO (DOSE-score).
timeFrame: 28-days.
Secondary outcomes:
measure: Development of major haemorrhage at 28 days
timeFrame: 28-days.
measure: Development of intracranial haemorrhage at 28 days
timeFrame: 28 days
measure: Mortality at 28 days
timeFrame: 28 days
measure: ECMO-free days at 28 days
timeFrame: 28 days
measure: Ventilator-free days at 28 days
timeFrame: 28 days
Other outcomes:
measure: Mortality at 180 days
timeFrame: 180 days
measure: Disability at 180 days
timeFrame: 180 days
measure: Functional Status at 180 days
timeFrame: 180 days
measure: Quality of Life at 180 days
timeFrame: 180 days
measure: ICU Length of Stay
timeFrame: 180 days
measure: Hospital Length of Stay
timeFrame: 180 days
measure: Number and Nature of SAEs
timeFrame: 28 days
measure: Mortality in ICU
timeFrame: 180 days
measure: Total Blood Products
timeFrame: 28 days
measure: Total RBC Units
timeFrame: 28 days
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
Study officials:
affiliation: Monash University
name: Carol Hodgson, PhD FACP FAHMS
role: STUDY_CHAIR
References: