Restrictive Versus Liberal Thresholds for RBC Transfusion in ECMO
NCT Number: NCT06560164
Acronym: TREC
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Transfusion|Red Blood Cell|Extracorporeal Membrane Oxygenation|Anemia|ECMO
Interventions: OTHER: Red Blood Cell transfusion
Sponsor: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 526
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-10-01
Completion Date: 2028-12-01
Locations: KU Leuven, medical IC, Leuven, Flemish Brabant, 3000, Belgium|KU Leuven, surgical IC, Leuven, Flemish Brabant, 3000, Belgium|CHU Charleroi, Charleroi, Hainaut, 6000, Belgium|Hôpital Erasme Brussels, Brussels, 1070, Belgium|Medisch Spectrum Twente (MST), Enschede, Drenthe, 7512 KZ, Netherlands|Maastricht Universitair Medisch Centrum+ (MUMC+), Maastricht, Limburg, 6229 HX, Netherlands|Amsterdam UMC, location AMC, Amsterdam, Noord-Holland, 1105 AZ, Netherlands|St. Antonius Ziekenhuis, Nieuwegein, Utrecht, 3435 CM, Netherlands|Leids Universitair Medisch Centrum (LUMC), Leiden, Zuid-Holland, 2333 ZA, Netherlands|Erasmus MC, Rotterdam, Zuid-Holland, 3015 GD, Netherlands|Universitair Medisch Centrum Groningen (UMCG), Groningen, 9713 GZ, Netherlands|Karolinska Universtiy Hospital, Stockholm, Stockholms Län, 171 76, Sweden

Summary:
Rationale: In patients supported with extracorporeal membrane oxygenation (ECMO), transfusion of red blood cells (RBC) is very common. This is possibly due to the application of liberal thresholds and the lack of evidence-based guidelines. Although RBC transfusion can be lifesaving, it is also a risk-bearing intervention with substantial risk for morbidity and mortality in this critically ill population. Also, with increasing scarcity, RBC transfusions are becoming more expensive. Furthermore, in the past decades it has been shown in several critically ill patient populations - not on ECMO - that maintaining a restrictive hemoglobin (Hb) threshold for RBC transfusion is non-inferior, including in cardiothoracic surgery, acute myocardial infarction and septic shock. Therefore, the investigators hypothesize that a restrictive transfusion threshold for RBC is safe to apply in patients on ECMO in comparison with a liberal transfusion threshold.

Objective: The primary objective of this trial is to study in a prospective randomized comparison whether a restrictive RBC transfusions strategy is non-inferior compared to a liberal strategy in patients on ECMO with respect to 90-day mortality.

Study design: Prospective multi-center randomized controlled non-inferiority trial.

Study population: Patients, 18 years or older, receiving ECMO.

Intervention: Restrictive RBC transfusion threshold: in case the Hb transfusion trigger of 7.0 g/dL (4.3 mmol/L) is reached, 1 RBC unit at a time will be transfused. The aimed Hb target range of the restrictive/intervention group will be 7.1 - 9.0 g/dL (4.3 - 5.6 mmol/L). Liberal RBC transfusion threshold: in case the Hb transfusion trigger of 9.0 g/dL (5.6 mmol/L) is reached, 1 RBC unit at a time will be transfused. Target range of the liberal group is defined as Hb 9.1 - 11.0 g/dL

Main study parameters/endpoints: The primary outcome parameter is 90-day all-cause mortality.

Secondary outcomes include: 1) proportion of patients on ECMO exposed to allogeneic RBC transfusion; 2) RBC volume infused per patient during ECMO; 3) reasons for RBC transfusion other than Hb triggers; 4) transfusion reactions; 5) time on ECMO; 6) length of hospital- and ICU-stay; 7) in-ICU morbidity; 8) quality of life (QoL), iMTA Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ) at 3, 6, 9, and 12 months; 9) costs related to a) transfusion, b) hospital admission and c) transfusion-related sequelae.

Primary Outcome Measures: 90-day all-cause mortality, The primary outcome measure is all-cause mortality within 90 days, i.e. the proportion of patients who die from any cause during this 90-day period following ECMO support., 90 days
Secondary Outcome Measures: In-hospital mortality, All-cause mortality during the hospital stay refers to the proportion of patients who died from any cause while they were still admitted to the hospital., 30 days|Duration, The duration of ECMO support, along with the length of ICU and hospital stays, are key metrics that quantify the total time a patient receives ECMO treatment, is in the intensive care unit, and remains in the hospital, measured in both days and hours., 30 days|Red blood cell transfusion exposure, The proportion of patients on ECMO who receive allogeneic red blood cell (RBC) transfusions., 30 days|Adherence, The number of adherence and non-adherence transfusion events., 30 days|EQ-5D-5L, A quality of life questionnaire assessing various domains including mobility, self-care, daily activities, and pain/discomfort, as well as emotional states like fear/sadness. Each domain is rated on a 5-point scale, where 1 indicates no problems and 5 indicates severe problems. Additionally, the questionnaire includes a EuroQol Visual Analogue Scale (EQ-VAS), which is a vertical scale ranging from 100 (best imaginable health) to 0 (worst imaginable health)., 3, 6, 9, and 12 months|Medical Consumption, The iMTA Medical Consumption Questionnaire (iMCQ) will be used to assess medical consumption and associated costs during the first year following ECMO support. This questionnaire collects detailed information on healthcare utilization, such as hospital visits, medications, medical procedures, and other related services, enabling an analysis of the overall costs incurred during the recovery period. The iMCQ does not include an outcome scale but focuses solely on quantifying the extent and cost of medical resources used., 3, 6, 9, and 12 months|Productivity Cost, The Productivity Cost Questionnaire (iPCQ) will be utilized to assess productivity loss during the first year following ECMO support. This questionnaire captures data on absenteeism, reduced efficiency at work, and lost productivity due to health-related issues. The iPCQ focuses exclusively on quantifying the extent of productivity loss without including an outcome scale, providing a clear picture of the economic impact associated with recovery in the first year post-ECMO., 3, 6, 9, and 12 months
Other Outcome Measures: In-ICU morbidity, All in-ICU morbidity, including neurological, cardiac, hemorrhagic, abdominal, renal, infection, peripheral, and transfusion-related complications., 30 days|Transfusion reasons, To evaluate the reasons for RBC transfusion beyond solely using hemoglobin (Hb) levels as the trigger., 30 days|Exposure to other transfusion products, The number of transfusions of other blood-derived products or coagulation factors, such as platelet concentrates., 30 days|Supportive therapy duration, The duration of supportive therapies, including invasive mechanical ventilation and renal replacement therapy, measured in both days and hours., 30 days