An interventional study of Red Blood Cell transfusion in Transfusion, Red Blood Cell and Extracorporeal Membrane Oxygenation, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). Recruiting at 14 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-14.
Sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Not applicable, Interventional, and Prevention
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.
Extracorporeal membrane oxygenation (ECMO) is used as a supportive method in case of temporary and potentially reversible cardiac or respiratory failure, refractory to conventional therapies. Over the past decades, application of ECMO has been increasing worldwide. As ECMO is generally used as a 'last resort' therapy, the population is vulnerable, and many complications can occur. Anemia occurs in >90% of the patients on ECMO, caused by many different patient-related, disease-related, and ECMO-related factors. Nevertheless, rationale for the recommended hemoglobin (Hb) thresholds for red blood cell (RBC) transfusion in this patient population is limited. This was recently confirmed by the members of the European Society of Intensive Care Medicine (ESICM), who concluded in their clinical practice guideline that no recommendation on transfusion thresholds can be made, since solid evidence is missing. The panel stated that this area is a research priority.
This lack of evidence-based guidelines may explain the high variance in Hb thresholds applied, as well as the thresholds in use being relatively liberal. As a result, transfusion of RBC is very common. Observational studies describe that almost 9 out of 10 patients receiving ECMO receive at least one RBC transfusion, and the total amount is very high. These numbers are even more remarkable when comparing to other patient populations in the Intensive Care Unit (ICU), in which 1 out of 4 patients receives RBC with way lesser amounts. One of the main arguments for using a liberal transfusion threshold in ECMO is the hypothesis that in patients receiving ECMO, tissue hypoxemia can develop due to decreased pulmonary oxygen intake (e.g., in pneumonia as indication for veno-venous [VV] ECMO), or decreased cardiac output (e.g., in myocardial infarction as indication for veno-arterial [VA] ECMO). By providing a larger Hb buffer, it is assumed that the oxygen delivery (DO2) will be preserved and the incidence of tissue hypoxemia will be reduced. However, evidence to either confirm or refute this hypothesis is lacking. Since ECMO ensures oxygenation and can provide a blood flow of up to 7 L/min, it can be assumed that ECMO fully compensates for the possible decrease in DO2.
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. In similar patient populations without ECMO, maintaining a restrictive RBC transfusion strategy (Hb 7.0 g/dL) has been proven non-inferior to a more liberal practice (Hb 9.0 g/dL). This includes randomized controlled trials (RCTs) in septic shock patients (comparable to patients on VV ECMO), cardiothoracic surgery patients, and even patients suffering from acute myocardial infarction and anemia (comparable to patients on VA ECMO). Although these conclusions are promising, they cannot directly be translated to patients supported by ECMO, although underlying conditions are similar. Moreover, RBC transfusions are expensive and donors are becoming more scarce. In this vulnerable critically ill patient population with an enhanced risk for transfusion related complications, it is of utmost importance to only administer a RBC transfusion when the benefits outweigh the risks.
As both anemia and transfusion are associated with poor outcomes, observational studies cannot answer the question whether a restrictive Hb threshold is non-inferior to a liberal strategy. There is a need to define general thresholds to improve the efficiency of indications for RBC transfusion in ECMO. Since one of the most commonly used triggers for RBC transfusion is Hb concentration, this forms the basis for our study to investigate whether it is non-inferior to maintain a restrictive transfusion threshold (intervention group: Hb 7 g/dL) compared to the current standard of 9 g/dL in patients on ECMO, independent of the mode.
This study is funded by ZonMW (Zorgonderzoek Medische Wetenschappen), part of the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek; the Dutch Organization for Scientific Research, Den Haag, the Netherlands), reference number 10390032310031.
1,810 studies on the registry are indexed under Anemia; 215 are open to participants now.
This study's planned enrollment of 526 is above the median of 117 across 1,336 interventional studies indexed under Anemia.
Browse Anemia studies →Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) is the lead sponsor of 532 studies on the registry; 183 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The restrictive strategy will consist of a transfusion Hb threshold of 7.0 g/dL, with a target Hb range of 7.1 - 9.0 g/dL. These thresholds are based on previous non-inferior trials in the patient populations in which VV ECMO (comparable to sepsis) and VA ECMO (cardiac surgery, acute myocardial infarction) are often applied.
Other: Red Blood Cell transfusion
The liberal strategy will consist of a transfusion Hb threshold of 9.0 g/dL, with a target Hb range of 9.1 - 11.0 g/dL. These Hb thresholds are based on thresholds that are currently used in ECMO.
Other: Red Blood Cell transfusion
When the appropriate Hb threshold is reached, patients in each group will have one unit of RBC administered at a time. Within 3 hours after the transfusion, a repeat Hb concentration will be measured. Each group will only be transfused when their Hb level falls below the transfusion threshold. In case of a outlier measurement, clinicians are advised to repeat the measurement. The RBC transfusion must take place within 4 hours when the Hb trigger was measured.
Also known as: RBC transfusion, pRBCs, packed Red Blood Cells
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.
Time frame: 90 days
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.
Time frame: 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.
Time frame: 30 days
Red blood cell transfusion exposure
The proportion of patients on ECMO who receive allogeneic red blood cell (RBC) transfusions.
Time frame: 30 days
Adherence
The number of adherence and non-adherence transfusion events.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 3, 6, 9, and 12 months
In-ICU morbidity
All in-ICU morbidity, including neurological, cardiac, hemorrhagic, abdominal, renal, infection, peripheral, and transfusion-related complications.
Time frame: 30 days
Transfusion reasons
To evaluate the reasons for RBC transfusion beyond solely using hemoglobin (Hb) levels as the trigger.
Time frame: 30 days
Exposure to other transfusion products
The number of transfusions of other blood-derived products or coagulation factors, such as platelet concentrates.
Time frame: 30 days
Supportive therapy duration
The duration of supportive therapies, including invasive mechanical ventilation and renal replacement therapy, measured in both days and hours.
Time frame: 30 days
Plan to share: Yes — The study protocol will be submitted for publication in a prominent journal.
Supporting information: Study protocol
Time frame: The protocol will be available after publication, expected within 1 year after the start of all participating centers.
Access criteria: Open access.
Data sharing details ↗ · ecmo-nl.com
Started Nov 2024 (actual). Primary completion is estimated for Oct 2027, 34 months after the start.
Of 163 non-industry interventional studies with no phase under Anemia, half reached primary completion within 18 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 30. This study's planned 34 months is above that.
Counting every sponsor, half of 177 studies reached it within 17 months; a quarter within 7 and three quarters within 29.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) →