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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05699005
Other study ID # 2020_04
Secondary ID 2021-A01925-36PH
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 18, 2023
Est. completion date December 18, 2025

Study information

Verified date January 2024
Source University Hospital, Lille
Contact Mouhamed MOUSSA, MD
Phone 0320445962
Email mouhamed.moussa@chru-lille.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This multicenter randomized controlled trial compare two transfusion strategies of red blood cells transfusion in patients supported by veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock. An individualized transfusion strategy based on ScVO2 level, is compared to a conventionnal strategy based on predefined hemoglobin threshold. The primary endpoint is the consumption of packed red blod cells, secondary endpoints are subgroup analysis, mortality, morbidity, and cost-effectiveness


Description:

Peripheral VA-ECMO is the mainstay of mechanical circulatory support in refractory cardiogenic shock. This treatment is associated with a high consumption of packed red blood cells (PRBCs), which can reach 1 to 3 units of PRBCs per day of support. The main reasons for such a high consumption of PRBCs are the very frequent hemorrhagic complications and the prevalence of anemias not directly related to the hemorrhagic episodes. These anemias are frequent during VA-ECMO support owing to hemolysis, hemodilution, previous bleeding episodes, thrombosis, etc. In order to restore, maintain, or increase oxygen delivery (DO2) to peripheral organs, RGCs are often performed when anemia is observed. Several studies have reported an association between transfusion of these PRBCs with morbidity and mortality in this ECMO setting. There is no appropriate strategy to reduce PRBC consumption, taking into account other determinants of DO2. In addition, there is currently no validated or consensus hemoglobin threshold to guide transfusion in this specific population. Furthermore, this predefined threshold-based approach may be inappropriate in the setting of VA-ECMO due to differences in DO2 requirements between patients based on their etiology, disease severity, and ECMO modality. In addition, large variations in DO2 can be observed in the same patient and between ECMO settings. Therefore, a more individualized strategy guided by a DO2 surrogate, ScVO2, may be more appropriate in this population. This ScVO2 approach has recently been shown to be associated with reduced PRBCs in two randomized controlled trials in cardiac surgery patients. The objective of this multicenter randomized controlled trial is to compare two red cell transfusion strategies in patients receiving extracorporeal veno-arterial membrane oxygenation for refractory cardiogenic shock. An individualized transfusion strategy based on ScVO2 level is compared with a conventional strategy based on a predefined hemoglobin threshold. The primary endpoint is red blood cell consumption, the secondary endpoints are subgroup analysis, mortality, morbidity, and cost-effectiveness.


Recruitment information / eligibility

Status Recruiting
Enrollment 238
Est. completion date December 18, 2025
Est. primary completion date September 18, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age of 18 and older, - supported by peripheral VA-ECMO - for cardiogenic shock - Life expentency >90 days - Central venous line available ScVO2 measurement Exclusion Criteria: - Pregnancy, - Lack of health insurance, - Opposition to blood transfusion, - Known congenital hemoglobin disease or disorder, - Metabolic alcaloosis with pH>7.8, - eCPR, - Legally incapacitated adults

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Packed Red Blood Cells (PRBCs)
Patient will recieve PRBCs transfusion only in case of ScVO2 level<65% after assessment of patient for optimisation of SaO2 targeting 100%, volume status, ECMO flow (increase to 20% in relevant), pain, anxiety and fever (body temperature >38°3). In both groups transfusion may be performed in case massive bleeding according to local protocols, STEMI, Hyperlactatemia >4 that can be related to oxygen demand and supply DO2/VO2 ratio impairement, in all groups, transfusion should be performed in case of hemolobin level <7g/dL or worsening of neurological condition (Increase in Neurological SOFA component of 1 and more) related to DO2/VO2 impairement.

Locations

Country Name City State
France Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universitaire de Lille Lille Nord

Sponsors (7)

Lead Sponsor Collaborator
University Hospital, Lille Amiens University Hospital, Centre hospitalier de Dunkerque, Centre Hospitalier de Lens, Centre Hospitalier Universitaire Dijon, University Hospital, Caen, University Hospital, Rouen

Country where clinical trial is conducted

France, 

References & Publications (17)

Aubron C, Cheng AC, Pilcher D, Leong T, Magrin G, Cooper DJ, Scheinkestel C, Pellegrino V. Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care. 2013 Apr 18;17(2):R73. doi: 10.1186/c — View Citation

Fischer MO, Guinot PG, Debroczi S, Huette P, Beyls C, Babatasi G, Bafi K, Guilbart M, Caus T, Lorne E, Dupont H, Hanouz JL, Diouf M, Abou-Arab O. Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial. Br J Anaesth. 2022 Jan;128(1):37-44. doi: 10.1016/j.bja.2021.09.037. Epub 2021 Nov 30. — View Citation

Guimbretiere G, Anselmi A, Roisne A, Lelong B, Corbineau H, Langanay T, Flecher E, Verhoye JP. Prognostic impact of blood product transfusion in VA and VV ECMO. Perfusion. 2019 Apr;34(3):246-253. doi: 10.1177/0267659118814690. Epub 2018 Nov 16. — View Citation

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 Inves — View Citation

Holst LB, Petersen MW, Haase N, Perner A, Wetterslev J. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ. 2015 Mar 24;350:h1354. do — View Citation

Holst LB. Benefits and harms of red blood cell transfusions in patients with septic shock in the intensive care unit. Dan Med J. 2016 Feb;63(2):B5209. — View Citation

Kim HS, Park S. Blood Transfusion Strategies in Patients Undergoing Extracorporeal Membrane Oxygenation. Korean J Crit Care Med. 2017 Feb;32(1):22-28. doi: 10.4266/kjccm.2016.00983. Epub 2017 Feb 28. — View Citation

Leffell MS, Kim D, Vega RM, Zachary AA, Petersen J, Hart JM, Rossert J, Bradbury BD. Red blood cell transfusions and the risk of allosensitization in patients awaiting primary kidney transplantation. Transplantation. 2014 Mar 15;97(5):525-33. doi: 10.1097 — View Citation

Lorusso R, Gelsomino S, Parise O, Mendiratta P, Prodhan P, Rycus P, MacLaren G, Brogan TV, Chen YS, Maessen J, Hou X, Thiagarajan RR. Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock in Elderly Patients: Trends in Applicat — View Citation

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. — View Citation

Mazzeffi M, Greenwood J, Tanaka K, Menaker J, Rector R, Herr D, Kon Z, Lee J, Griffith B, Rajagopal K, Pham S. Bleeding, Transfusion, and Mortality on Extracorporeal Life Support: ECLS Working Group on Thrombosis and Hemostasis. Ann Thorac Surg. 2016 Feb; — View Citation

Mazzeffi MA, Tanaka K, Roberts A, Rector R, Menaker J, Kon Z, Deatrick KB, Kaczorowski D, Griffith B, Herr D. Bleeding, Thrombosis, and Transfusion With Two Heparin Anticoagulation Protocols in Venoarterial ECMO Patients. J Cardiothorac Vasc Anesth. 2019 — View Citation

Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, Fergusson D, Follea G, French C, Frey KP, Gammon R, Levy JH, Murphy MF, Ozier Y, Pavenski K, So-Osman C, Tiberghien P, Volmink J, Waters JH, — View Citation

Rohde JM, Dimcheff DE, Blumberg N, Saint S, Langa KM, Kuhn L, Hickner A, Rogers MA. Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA. 2014 Apr 2;311(13):1317-26. doi: 10.1001/jama.2014.2726. Er — View Citation

Vallet B, Robin E, Lebuffe G. Venous oxygen saturation as a physiologic transfusion trigger. Crit Care. 2010;14(2):213. doi: 10.1186/cc8854. Epub 2010 Mar 9. — View Citation

Vlaar AP, Hofstra JJ, Determann RM, Veelo DP, Paulus F, Kulik W, Korevaar J, de Mol BA, Koopman MM, Porcelijn L, Binnekade JM, Vroom MB, Schultz MJ, Juffermans NP. The incidence, risk factors, and outcome of transfusion-related acute lung injury in a coho — View Citation

Zeroual N, Blin C, Saour M, David H, Aouinti S, Picot MC, Colson PH, Gaudard P. Restrictive Transfusion Strategy after Cardiac Surgery. Anesthesiology. 2021 Mar 1;134(3):370-380. doi: 10.1097/ALN.0000000000003682. — View Citation

* Note: There are 17 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Number of PRBCs transfused per VA-ECMO day of support Total number of PRBCs transfused during support adjusted for VA- ECMO duration From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Number of PRBCs transfused per VA-ECMO day of support in postcardiotomy patients Total number of PRBCs transfused during support adjusted for VA- ECMO duration in patients that underwent cardiac surgery From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Total number of PRBCs transfused during the 28-day following cannulation Total number of PRBCs transfused during the 28-day following cannulation From randomisation until 28 days
Secondary Changes in hemoglobin levels during VA-ECMO support daily hemoglobin levels From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Changes in ScVO2 levels during VA-ECMO support daily ScVO2 levels From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Changes in vosoactive index score levels during VA-ECMO support daily vasoactive index score levels From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Mortality under ECMO support All cause mortality before ECMO weaning From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary 90-day Mortality All cause mortality from cannulation untill 90 days 90 days from cannulation
Secondary ECMO removal modalities Proportion of patients that according to each reason for removal ( Recovery, heart transplantation, Left ventricle or biventricle assist device or death under support) From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Duration of mechanical ventilation Duration of mechnanical ventilation from cannulation untill 28 days 28 days from cannulation
Secondary Proportion of patient that received a renal replacement therapy and its duration Number of patient that underwent a renal replacement therapy and duration of renal replacement therapy from cannulation untill 28 days 28 days from cannulation
Secondary Duration of vasoactive support Duration of vasoactive drug support from cannulation untill 28 days 28 days from cannulation
Secondary Hospital lenght of stay Length of stay from cannulation censored at 90 day 28 days from cannulation
Secondary HLA immuno-sensitisation Proportion of HLA immunosensitisation occuring after cannulation 28 and 90 days from cannulation
Secondary Proportion of patient with Transfusion related immunologic ( non HLA-related) complications Transfusion related acute lung injury, hemolytic anemia, irregular antibodies From randomisation until 28 days
Secondary Proportion of patients with nex onset of sepsis Sepsis is defined according to Surviving Sepsis Campaign guideline From randomisation until 28 days
Secondary Proportion of patients with a new onset of acute kidney injury Acute kidney injury is define according to KDIGO classification From randomisation until 28 days
Secondary Proportion of patients with liver failure Liver failure is defined as Hepatic component of SOFA score, Transaminasis Levels From randomisation until 28 days
Secondary Ischemic stroke Ischemic stroke is defined as clinical symptoms confirmed by aCT Scan of MRI imaging From randomisation until 28 days
Secondary Myocardial infarction According to the Universal definition of myocardial infarction, ESC guidelines From randomisation until 28 days
Secondary Pulmonary oedema Dignose by the attending physician based on (Dyspnae, Thoracic X-rays), bowel ischemia ( Abdominal CT or endoscopy proven) From randomisation until 28 days
Secondary Anaphylactic complications Anaphylaxis defined according to Ring and Messer Classification From randomisation until 28 days
Secondary Bowel Ischemia Proven by Abdominal CT or endoscopy From randomisation until 28 days
Secondary Cost effectiveness analysis Actual costs at 28 and 90 days and modelisation for 5 years 28 days, 90 days and 5 years from randomisation
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