Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO

Anemia Clinical Trial

— ICONE  

Official title:

Comparison of an Individualized Transfusion Strategy to a Conventional Strategy in Patients Undergoing Peripheral Veno-arterial ECMO for Refractory Cardiogenic Shock: a Randomized Controlled Trial - ICONE

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
• 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
• 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

Related Conditions & MeSH terms

• Anemia
• Cardiogenic Shock
• Extracorporeal Membrane Oxygenation
• Oxygen Delivery
• Shock
• Shock, Cardiogenic
• Transfusion Related Complication

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 all — Click 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