Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06560164
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-13
Brief Title:
Restrictive Versus Liberal Thresholds for RBC Transfusion in ECMO
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Restrictive Versus Liberal Thresholds for Red Blood Cell Transfusion in ExtraCorporeal Membrane Oxygenation - the TREC Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TREC
Brief 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 70 gdL 43 mmolL is reached 1 RBC unit at a time will be transfused The aimed Hb target range of the restrictiveintervention group will be 71 - 90 gdL 43 - 56 mmolL Liberal RBC transfusion threshold in case the Hb transfusion trigger of 90 gdL 56 mmolL is reached 1 RBC unit at a time will be transfused Target range of the liberal group is defined as Hb 91 - 110 gdL
Main study parametersendpoints 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
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 70 gdL 43 mmolL is reached 1 RBC unit at a time will be transfused The aimed Hb target range of the restrictiveintervention group will be 71 - 90 gdL 43 - 56 mmolL Liberal RBC transfusion threshold in case the Hb transfusion trigger of 90 gdL 56 mmolL is reached 1 RBC unit at a time will be transfused Target range of the liberal group is defined as Hb 91 - 110 gdL
Main study parametersendpoints 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
Detailed Description:
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 eg in pneumonia as indication for veno-venous VV ECMO or decreased cardiac output eg 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 Lmin 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 70 gdL has been proven non-inferior to a more liberal practice Hb 90 gdL 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 gdL compared to the current standard of 9 gdL 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
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 eg in pneumonia as indication for veno-venous VV ECMO or decreased cardiac output eg 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 Lmin 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 70 gdL has been proven non-inferior to a more liberal practice Hb 90 gdL 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 gdL compared to the current standard of 9 gdL 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None