Red Blood Cell Transfusion in ECMO - A Feasibility Trial (ROSETTA)

Extracorporeal Membrane Oxygenation (ECMO) is an invasive and resource intense treatment used to support critically ill patients who have suffered severe cardiac arrest, cardiac failure or respiratory failure (including severe cases of COVID-19). ECMO acts as a mechanical circulatory support temporarily replacing the function of the heart or lungs by oxygenating blood and removing carbon dioxide, allowing time for these organs to recover. Many critically ill patients, including those on ECMO, have an increased risk of bleeding and reduced production/increased destruction of red blood cells (RBCs). This can lead to anaemia (haemoglobin levels <120 g/l), a condition where the body lacks enough healthy RBCs to carry enough oxygen to the body's tissues. Therefore, patients on ECMO frequently require RBC transfusion, with clinicians having to decide if administering an RBC transfusion (with its associated risks) is higher than tolerating complications of anaemia.

ROSETTA is a feasibility study that aims to determine the safety and feasibility of randomizing patients on ECMO to a restrictive RBC transfusion strategy (maintain Hb concentration above 70g/L) or to a more liberal transfusion strategy (maintain Hb concentration above 90g/L). Feasibility is defined as the ability to achieve a mean separation of at least 10g/L between the average lowest daily haemoglobin values in the two study groups.

Study Overview

• Status: Recruiting
• Conditions: Functional Status; Cognitive Ability, General; Disability Physical; Extracorporeal Membrane Oxygenation Complication; Blood Loss Anemia
• Intervention / Treatment: Other: Red Blood Cell Transfusion; Other: Red Blood Cell Transfusion

Detailed Description

A recent Cochrane analysis recommended a transfusion strategy that minimises the use of RBC transfusions in critically ill patients (by tolerating anaemia to avoid the adverse effects of an RBC transfusion). However, the analysis acknowledges that the degree of anaemia which can be tolerated by such patients is unknown, especially in patients suffering from conditions that limit oxygen delivery to the organs (like cardiac disease). As a result, the Australian Blood Authority's guidelines recommend an RBC transfusion to a patient at an Hb concentration of less than 70 g/L, while a transfusion at a Hb between 70 and 90 g/L should be based on the need to relieve clinical signs and symptoms of anaemia. However, this range is broad, and many studies in the general critically ill cohort have shown lower transfusion triggers are non-inferior to higher transfusion triggers.

No studies have been completed directly evaluating transfusion triggers in the ECMO patient cohort. ECMO patients differ to the general critically ill cohort as they have different physiological requirements, are at higher-risk for poor outcomes, and have an increased requirement for transfusions. Hb is a key driver of oxygen delivery (DO2), and critically ill ECMO patients are more commonly exposed to low DO2 due to low cardiac output and borderline oxygenation. Therefore, studies must be done to evaluate the optimal transfusion trigger/s (as determined by Hb concentration) that optimise mortality and long-term outcomes of ECMO patients.

Should the ROSSETTA Pilot results indicate adequate separation of at least 10g/L between the two study groups, and that patient safety has not been adversely affected by the trial methods, feasibility will be deemed confirmed and the protocol not in need of modification prior to full trial commencement. At this point the ROSETTA Pilot will be transitioned into the Red Blood Cell Transfusion Domain, within RECOMMEND Platform Trial. The Primary and Secondary outcomes of the trial at large, will be answered during this stage.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Curtis Hopkins, B.BioMed, MPH, MHA; Phone Number: +61 3 9903 0343; Email: anzicrc@monash.edu

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
      • Contact: Heidi Buhr; Phone Number: +61 2 9515 6007; Email: heidi.buhr@health.nsw.gov.au
      • Principal Investigator: Timothy Southwood
    • Sydney, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent's Health Sydney
      • Contact: Hergen Buscher, A/Prof; Email: hergen.buscher@svhs.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients receiving ECMO
• Age: 18 years or older

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
• ECMO treatment for more than 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 is defined as the arrival time into the initial ICU.
• The treating physician anticipates that ECMO treatment will cease before the end of tomorrow
• Where the treating physician deems the study is not in the patient's best interest
• Where the treating physician has concern regarding patient ability to tolerate restrictive or liberal transfusion trigger thresholds
• Patients actively listed for a solid organ transplant
• Patients who are suspected or confirmed to be pregnant
• Previous ECMO treatment during the same hospital admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Restrictive Transfusion Trigger Group; 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.	Other: Red Blood Cell Transfusion; Following randomisation, if a patient's Hb concentration reads ≤ 70g/L, one unit of RBC will be transfused within 12 hours of the result becoming available. Additional units can be prescribed if required to raise the Hb concentration to above 70g/L. A transfusion above the restrictive threshold of 70g/L is discouraged.; Other: Red Blood Cell Transfusion; Following randomisation, if a patient's Hb concentration reads ≤ 90g/L, one or more units of RBC will be transfused in order to raise the Hb concentration to greater than 90g/L within 12 hours of the result becoming available. A decision not to transfuse below the threshold of 90g/L is discouraged.
Active Comparator: Liberal Transfusion Trigger Group; 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	Other: Red Blood Cell Transfusion; Following randomisation, if a patient's Hb concentration reads ≤ 70g/L, one unit of RBC will be transfused within 12 hours of the result becoming available. Additional units can be prescribed if required to raise the Hb concentration to above 70g/L. A transfusion above the restrictive threshold of 70g/L is discouraged.; Other: Red Blood Cell Transfusion; Following randomisation, if a patient's Hb concentration reads ≤ 90g/L, one or more units of RBC will be transfused in order to raise the Hb concentration to greater than 90g/L within 12 hours of the result becoming available. A decision not to transfuse below the threshold of 90g/L is discouraged.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in average lowest daily Hb concentration	Primary Outcome Measure	From date of randomization to the end of the intervention (assessed up to day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrolment Rate	Feasibility Outcome	through study completion, an average of 2 years
Reasons for not entering eligible patients into the study	Feasibility Outcome	through study completion, an average of 2 years
Mean pre-transfusion Hb concentration immediately prior to an RBC transfusion	Feasibility Outcome	through study completion, an average of 2 years
Proportion of RBC transfusions given according to allocated trigger	Feasibility Outcome	through study completion, an average of 2 years
Time from measured Hb trigger value to transfusion	Feasibility Outcome	through study completion, an average of 2 years
Number of RBC transfusions given prior to randomization	Feasibility Outcome	through study completion, an average of 2 years
Frequency for not transfusing a patient who has reached a transfusion trigger	Feasibility Outcome	through study completion, an average of 2 years
Reason/s for not transfusing a patient who has reached a transfusion trigger	Feasibility Outcome	through study completion, an average of 2 years
Number of protocol deviations	Feasibility Outcome	through study completion, an average of 2 years
Number and nature of Serious Adverse Events (SAEs)	Safety and effectiveness outcome	through study completion, an average of 2 years
Total blood products used	Safety and effectiveness outcome	through study completion, an average of 2 years
Major bleeding events (defined by ISTH criteria)	Safety and effectiveness outcome	through study completion, an average of 2 years
Clinically relevant non-major bleeding events: GI haemorrhage, peripheral cannulation site bleeding, mediastinal cannulation site bleeding, surgical site bleeding	Safety and effectiveness outcome	through study completion, an average of 2 years
Venous and arterial thromboembolic events	Safety and effectiveness outcome	through study completion, an average of 2 years
New onset renal replacement therapy (RRT) during ECMO	Safety and effectiveness outcome	through study completion, an average of 2 years
ECMO free days at day 60	Safety and effectiveness outcome	60 days
ICU free days at day 60	Safety and effectiveness outcome	60 days
Patient Reported Outcome Measure - WHODAS 2.0	Disability Safety and effectiveness outcome	6 months
Patient Reported Outcome Measure - IADL	Independent Activities of Daily Living Safety and effectiveness outcome	6 months
Patient Reported Outcome Measure - ADL	Activity of Daily Living Safety and effectiveness outcome	6 months
Patient Reported Outcome Measure - MoCA BLIND	Cognitive Function Safety and effectiveness outcome	6 months
Patient Reported Outcome Measure - EQ-5D-5L	Quality of Life Safety and effectiveness outcome	6 months
Patient Reported Outcome Measure - mRS	Degree of Disability Safety and effectiveness outcome	6 months

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Investigators: Principal Investigator: Aidan Burrell, MBBS, Monash University; Principal Investigator: Hergen Buscher, MBBS, St Vincent's Hospital, Sydney; Principal Investigator: Zoe McQuilten, PhD, Monash University; Principal Investigator: Alistair Nichol, PhD, Monash University; Principal Investigator: Mark Dennis, MBBS, Royal Prince Alfred Hospital, Sydney, Australia; Principal Investigator: Timothy Southwood, MBBS, Royal Prince Alfred Hospital, Sydney, Australia; Principal Investigator: Alisa Higgins, PhD, Monash University; Principal Investigator: Sally Newman, Nursing, St Vincent's Hospital, Sydney; Principal Investigator: Thao Le, PhD, Monash University; Principal Investigator: Carol Hodgson, PhD, Monash University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Actual): January 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: critical care; safety; bleeding; ICU; Australia; ECMO; feasibility; intensive care; transfusion; blood transfusion; Hb; RBC transfusion; blood products; Hb values
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: ANZIC-RC/HB001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patient data is de-identified and only aggregate summaries published.

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