Restrictive Versus Liberal Thresholds for RBC Transfusion in ECMO
NCT ID: NCT06560164
Last Updated: 2025-04-08
Study Results
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Basic Information
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RECRUITING
NA
526 participants
INTERVENTIONAL
2024-11-26
2029-10-01
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
Study population: Patients, 18 years or older, receiving ECMO (see additional details below).
Randomization will be stratified by:
* Center;
* ECMO mode, divided by:
* VV ECMO (or triple cannulation methods with primarily a pulmonary indication);
* VA ECMO (or triple cannulation methods with primarily a cardiac indication or extracorporeal cardiopulmonary resuscitation \[ECPR\]).
Intervention:
1. 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.
2. 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.
PREVENTION
NONE
Study Groups
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Restrictive strategy
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.
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.
Liberal strategy
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.
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.
Interventions
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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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Is receiving ECMO;
* (Deferred) informed consent.
Exclusion Criteria
* Inability to receive blood products;
* (Known) decline to blood transfusions (e.g., Jehovah's Witnesses);
* Extracorporeal carbon dioxide removal (ECCO2R) using low blood flow devices or pumpless devices (i.e., MINILUNG ®, PrismaLung+);
* Received ECMO over 48h before screening for eligibility.
18 Years
ALL
No
Sponsors
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ZonMw: The Netherlands Organisation for Health Research and Development
OTHER
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
OTHER
Responsible Party
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A.P.J. Vlaar
Prof. Dr.
Principal Investigators
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Alexander P.J. Vlaar, PhD
Role: PRINCIPAL_INVESTIGATOR
Amsterdam UMC, location AMC
Locations
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Hôpital Erasme Brussels
Brussels, Brussels Capital, Belgium
KU Leuven, medical IC
Leuven, Flemish Brabant, Belgium
KU Leuven, surgical IC
Leuven, Flemish Brabant, Belgium
CHU Charleroi
Charleroi, Hainaut, Belgium
Medisch Spectrum Twente (MST)
Enschede, Drenthe, Netherlands
Maastricht Universitair Medisch Centrum+ (MUMC+)
Maastricht, Limburg, Netherlands
Amsterdam UMC, location AMC
Amsterdam, North Holland, Netherlands
Universitair Medisch Centrum Groningen (UMCG)
Groningen, Provincie Groningen, Netherlands
Leids Universitair Medisch Centrum (LUMC)
Leiden, South Holland, Netherlands
Erasmus MC
Rotterdam, South Holland, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, Utrecht, Netherlands
Karolinska Universtiy Hospital
Stockholm, Stockholm County, Sweden
Countries
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Central Contacts
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Facility Contacts
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References
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Related Links
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Extracorporeal Life Support Organization. Extracorporeal Life Support Organization ECLS Registry Report Overall Outcomes. 2019
Additional study information and progress overview
Other Identifiers
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NL84295.018.23
Identifier Type: OTHER
Identifier Source: secondary_id
84295
Identifier Type: OTHER
Identifier Source: secondary_id
B3222022001258
Identifier Type: REGISTRY
Identifier Source: secondary_id
2023-07691-01
Identifier Type: REGISTRY
Identifier Source: secondary_id
10390032310031
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
NL84295.018.23
Identifier Type: -
Identifier Source: org_study_id
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