Restrictive Versus Liberal Thresholds for RBC Transfusion in ECMO (TREC)

Restrictive Versus Liberal Thresholds for Red Blood Cell Transfusion in ExtraCorporeal Membrane Oxygenation - the TREC Study

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.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Extracorporeal Membrane Oxygenation; Transfusion; ECMO; Red Blood Cell
• Intervention / Treatment: Other: Red Blood Cell transfusion

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 (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.

• Study Type: Interventional
• Enrollment (Estimated): 526
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexander P.J. Vlaar, PhD; Phone Number: 020 566 9111; Email: a.p.vlaar@amsterdamumc.nl
• Study Contact Backup: Name: Stefan F. van Wonderen, MD; Phone Number: 020 566 9111; Email: s.vanwonderen@amsterdamumc.nl

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Hôpital Erasme Brussels
    • Contact: Fabio Taccone, PhD; Phone Number: +32 2 555 31 11; Email: Fabio.Taccone@ulb.be
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Recruiting
      • KU Leuven, medical IC
      • Contact: Greet Hermans, PhD; Phone Number: +32 16 33 22 11; Email: greet.hermans@uzleuven.be
    • Leuven, Flemish Brabant, Belgium, 3000
      • Recruiting
      • KU Leuven, surgical IC
      • Contact: Dieter Dauwe, PhD; Phone Number: +32 16 33 22 11; Email: dieter.dauwe@uzleuven.be
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Recruiting
      • CHU Charleroi
      • Contact: Michaël Piagnerelli, PhD; Phone Number: 071 92 11 11; Email: michael.Piagnerelli@ulb.be
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen (UMCG)
    • Contact: Walter van den Bergh, PhD; Phone Number: 050 361 6161; Email: w.m.van.den.bergh@umcg.nl
  • Drenthe
    • Enschede, Drenthe, Netherlands, 7512 KZ
      • Recruiting
      • Medisch Spectrum Twente (MST)
      • Contact: Wytze Vermeijden, PhD; Phone Number: 053 487 2000; Email: j.vermeijden@mst.nl
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Recruiting
      • Maastricht Universitair Medisch Centrum+ (MUMC+)
      • Contact: Marcel van de Poll, PhD; Phone Number: 043 387 6543; Email: marcel.vande.poll@mumc.nl
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC, location AMC
      • Contact: Alexander P.J. Vlaar, PhD; Phone Number: 020 566 9111; Email: a.p.vlaar@amsterdamumc.nl
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • Recruiting
      • St. Antonius Ziekenhuis
      • Contact: Erik Scholten, MD; Phone Number: 088 320 3000; Email: e.scholten@antoniusziekenhuis.nl
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Not yet recruiting
      • Leids Universitair Medisch Centrum (LUMC)
      • Contact: Carlos Elzo Kraemer, MD; Phone Number: 071 526 9111; Email: c.v.elzo_kraemer@lumc.nl
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Not yet recruiting
      • Erasmus MC
      • Contact: Christiaan Meuwese, PhD; Phone Number: 010 704 0704; Email: c.meuwese@erasmusmc.nl
• Sweden
  • Stockholms län
    • Stockholm, Stockholms län, Sweden, 171 76
      • Not yet recruiting
      • Karolinska Universtiy Hospital
      • Contact: Lars M. Broman, PhD; Phone Number: +46 8 123 70 000; Email: lars.broman@regionstockholm.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is aged 18 years or older;
• Is receiving ECMO;
• (Deferred) informed consent.

Exclusion Criteria:

• Not expected to survive for 24 hours when assessed;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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.; Other Names: RBC transfusion; pRBCs; packed Red Blood Cells
Active Comparator: 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.	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.; Other Names: RBC transfusion; pRBCs; packed Red Blood Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Alexander P.J. Vlaar, PhD, Amsterdam UMC, location AMC

Publications and helpful links

General Publications

• Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care. 2016 Dec;6(1):97. doi: 10.1186/s13613-016-0196-7. Epub 2016 Oct 6.
• Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D; ABC (Anemia and Blood Transfusion in Critical Care) Investigators. Anemia and blood transfusion in critically ill patients. JAMA. 2002 Sep 25;288(12):1499-507. doi: 10.1001/jama.288.12.1499.
• Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. doi: 10.1056/NEJM199902113400601. Erratum In: N Engl J Med 1999 Apr 1;340(13):1056.
• Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, McGuinness S, Royse A, Carrier FM, Young PJ, Villar JC, Grocott HP, Seeberger MD, Fremes S, Lellouche F, Syed S, Byrne K, Bagshaw SM, Hwang NC, Mehta C, Painter TW, Royse C, Verma S, Hare GMT, Cohen A, Thorpe KE, Juni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. N Engl J Med. 2017 Nov 30;377(22):2133-2144. doi: 10.1056/NEJMoa1711818. Epub 2017 Nov 12.
• Gong MN, Thompson BT, Williams P, Pothier L, Boyce PD, Christiani DC. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med. 2005 Jun;33(6):1191-8. doi: 10.1097/01.ccm.0000165566.82925.14.
• Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, MacIntyre NR, Shabot MM, Duh MS, Shapiro MJ. The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States. Crit Care Med. 2004 Jan;32(1):39-52. doi: 10.1097/01.CCM.0000104112.34142.79.
• Kracalik I, Mowla S, Basavaraju SV, Sapiano MRP. Transfusion-related adverse reactions: Data from the National Healthcare Safety Network Hemovigilance Module - United States, 2013-2018. Transfusion. 2021 May;61(5):1424-1434. doi: 10.1111/trf.16362. Epub 2021 Apr 20.
• Hayden SJ, Albert TJ, Watkins TR, Swenson ER. Anemia in critical illness: insights into etiology, consequences, and management. Am J Respir Crit Care Med. 2012 May 15;185(10):1049-57. doi: 10.1164/rccm.201110-1915CI. Epub 2012 Jan 26.
• Gattinoni L, Carlesso E, Langer T. Clinical review: Extracorporeal membrane oxygenation. Crit Care. 2011;15(6):243. doi: 10.1186/cc10490. Epub 2011 Dec 8.
• Makdisi G, Wang IW. Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology. J Thorac Dis. 2015 Jul;7(7):E166-76. doi: 10.3978/j.issn.2072-1439.2015.07.17.
• Vlaar AP, Oczkowski S, de Bruin S, Wijnberge M, Antonelli M, Aubron C, Aries P, Duranteau J, Juffermans NP, Meier J, Murphy GJ, Abbasciano R, Muller M, Shah A, Perner A, Rygaard S, Walsh TS, Guyatt G, Dionne JC, Cecconi M. Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine. Intensive Care Med. 2020 Apr;46(4):673-696. doi: 10.1007/s00134-019-05884-8. Epub 2020 Jan 7.
• de Bruin S, Scheeren TWL, Bakker J, van Bruggen R, Vlaar APJ; Cardiovascular Dynamics Section and Transfusion Guideline Task Force of the ESICM. Transfusion practice in the non-bleeding critically ill: an international online survey-the TRACE survey. Crit Care. 2019 Sep 11;23(1):309. doi: 10.1186/s13054-019-2591-6.
• Martucci G, Grasselli G, Tanaka K, Tuzzolino F, Panarello G, Schmidt M, Bellani G, Arcadipane A. Hemoglobin trigger and approach to red blood cell transfusions during veno-venous extracorporeal membrane oxygenation: the international TRAIN-ECMO survey. Perfusion. 2019 Apr;34(1_suppl):39-48. doi: 10.1177/0267659119830526.
• Raasveld SJ, Karami M, van den Bergh WM, Oude Lansink-Hartgring A, van der Velde F, Maas JJ, van de Berg P, de Haan M, Lorusso R, Delnoij TSR, Dos Reis Miranda D, Mandigers L, Scholten E, Overmars M, Silvio Taccone F, Brasseur A, Dauwe DF, De Troy E, Hermans G, Meersseman P, Pappalardo F, Fominskiy E, Ivancan V, Bojcic R, de Metz J, van den Bogaard B, Donker DW, Meuwese CL, de Bakker M, Reddi B, de Bruin S, Lagrand WK, Henriques JPS, Broman LM, Vlaar APJ. RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study. Crit Care Med. 2022 Feb 1;50(2):224-234. doi: 10.1097/CCM.0000000000005398.
• Bosboom JJ, Klanderman RB, Zijp M, Hollmann MW, Veelo DP, Binnekade JM, Geerts BF, Vlaar APJ. Incidence, risk factors, and outcome of transfusion-associated circulatory overload in a mixed intensive care unit population: a nested case-control study. Transfusion. 2018 Feb;58(2):498-506. doi: 10.1111/trf.14432. Epub 2017 Dec 13.
• Murphy GJ, Pike K, Rogers CA, Wordsworth S, Stokes EA, Angelini GD, Reeves BC; TITRe2 Investigators. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med. 2015 Mar 12;372(11):997-1008. doi: 10.1056/NEJMoa1403612. Erratum In: N Engl J Med. 2015 Jun 4;372(23):2274. doi: 10.1056/NEJMx150020.
• Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, Lemesle G, Cachanado M, Durand-Zaleski I, Arnaiz JA, Martinez-Selles M, Silvain J, Ariza-Sole A, Ferrari E, Calvo G, Danchin N, Avendano-Sola C, Frenkiel J, Rousseau A, Vicaut E, Simon T, Steg PG; REALITY Investigators. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial. JAMA. 2021 Feb 9;325(6):552-560. doi: 10.1001/jama.2021.0135.
• Holst LB, Haase N, Wetterslev J, Wernerman J, Aneman A, Guttormsen AB, Johansson PI, Karlsson S, Klemenzson G, Winding R, Nebrich L, Albeck C, Vang ML, Bulow HH, Elkjaer JM, Nielsen JS, Kirkegaard P, Nibro H, Lindhardt A, Strange D, Thormar K, Poulsen LM, Berezowicz P, Badstolokken PM, Strand K, Cronhjort M, Haunstrup E, Rian O, Oldner A, Bendtsen A, Iversen S, Langva JA, Johansen RB, Nielsen N, Pettila V, Reinikainen M, Keld D, Leivdal S, Breider JM, Tjader I, Reiter N, Gottrup U, White J, Wiis J, Andersen LH, Steensen M, Perner A. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial. Trials. 2013 May 23;14:150. doi: 10.1186/1745-6215-14-150.
• Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016 Oct 12;10(10):CD002042. doi: 10.1002/14651858.CD002042.pub4.
• Docherty AB, Turgeon AF, Walsh TS. Best practice in critical care: anaemia in acute and critical illness. Transfus Med. 2018 Apr;28(2):181-189. doi: 10.1111/tme.12505. Epub 2018 Jan 25.
• Spinelli E, Bartlett RH. Anemia and Transfusion in Critical Care: Physiology and Management. J Intensive Care Med. 2016 Jun;31(5):295-306. doi: 10.1177/0885066615571901. Epub 2015 Feb 18.
• Vlaar APJ, Toy P, Fung M, Looney MR, Juffermans NP, Bux J, Bolton-Maggs P, Peters AL, Silliman CC, Kor DJ, Kleinman S. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019 Jul;59(7):2465-2476. doi: 10.1111/trf.15311. Epub 2019 Apr 16.
• Wiersum-Osselton JC, Whitaker B, Grey S, Land K, Perez G, Rajbhandary S, Andrzejewski C Jr, Bolton-Maggs P, Lucero H, Renaudier P, Robillard P, Santos M, Schipperus M. Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study. Lancet Haematol. 2019 Jul;6(7):e350-e358. doi: 10.1016/S2352-3026(19)30080-8. Epub 2019 May 9.

Helpful Links

• Extracorporeal Life Support Organization. Extracorporeal Life Support Organization ECLS Registry Report Overall Outcomes. 2019
• Additional study information and progress overview

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; ECMO; Red Blood Cell; Transfusion; Extracorporeal Membrane Oxygenation
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: NL84295.018.23 (Other Identifier: IRB Amsterdam UMC); 84295 (Other Identifier: ABR (Dutch: General Assessment and Registration Form)); B3222022001258 (Registry Identifier: Belgium Registration Number); 2023-07691-01 (Registry Identifier: Swedish Registration Number); 10390032310031 (Other Grant/Funding Number: ZonMW)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol will be submitted for publication in a prominent journal.
• IPD Sharing Time Frame: The protocol will be available after publication, expected within 1 year after the start of all participating centers.
• IPD Sharing Access Criteria: Open access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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