Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO (ICONE)

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

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

Study Overview

• Status: Recruiting
• Conditions: Anemia; Extracorporeal Membrane Oxygenation; Cardiogenic Shock; Transfusion Related Complication; Oxygen Delivery
• Intervention / Treatment: Drug: Packed Red Blood Cells (PRBCs)

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 238
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mouhamed MOUSSA, MD; Phone Number: 0320445962; Email: mouhamed.moussa@chru-lille.fr

Study Locations

• France
  • Nord
    • Lille, Nord, France, 59000
      • Recruiting
      • Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universitaire de Lille
      • Contact: Mouhamed D Moussa, MD; Phone Number: =33659248780; Email: mouhamed.moussa@chru-lille.fr
      • Contact: Julien Tabareau; Phone Number: 0320445962; Email: julien.tabareau@chru-lille.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Individulised transfusion strategy group; Patients will recieve red blood cells transfusion in case of a drop of ScVO2 <65% after an assessment for the optimisation of SaO2 normalisation (SaO2>94%), volume optimisation, ECMO output increase, Fever (body temperature 38°3 C°), Anxiety and Pain	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.; Other Names: ScVO2 assesment to guide transfusion
Active Comparator: Conventionnal transfusion strategy group; Transfusion will be performed in case of a hemoglobin drop <9 g/dL	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.; Other Names: ScVO2 assesment to guide transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Changes in hemoglobin levels during VA-ECMO support	daily hemoglobin levels	From randomisation until VA-ECMO weanning assessed up to 28 days
Changes in ScVO2 levels during VA-ECMO support	daily ScVO2 levels	From randomisation until VA-ECMO weanning assessed up to 28 days
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
Mortality under ECMO support	All cause mortality before ECMO weaning	From randomisation until VA-ECMO weanning assessed up to 28 days
90-day Mortality	All cause mortality from cannulation untill 90 days	90 days from cannulation
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
Duration of mechanical ventilation	Duration of mechnanical ventilation from cannulation untill 28 days	28 days from cannulation
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
Duration of vasoactive support	Duration of vasoactive drug support from cannulation untill 28 days	28 days from cannulation
Hospital lenght of stay	Length of stay from cannulation censored at 90 day	28 days from cannulation
HLA immuno-sensitisation	Proportion of HLA immunosensitisation occuring after cannulation	28 and 90 days from cannulation
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
Proportion of patients with nex onset of sepsis	Sepsis is defined according to Surviving Sepsis Campaign guideline	From randomisation until 28 days
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
Proportion of patients with liver failure	Liver failure is defined as Hepatic component of SOFA score, Transaminasis Levels	From randomisation until 28 days
Ischemic stroke	Ischemic stroke is defined as clinical symptoms confirmed by aCT Scan of MRI imaging	From randomisation until 28 days
Myocardial infarction	According to the Universal definition of myocardial infarction, ESC guidelines	From randomisation until 28 days
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
Anaphylactic complications	Anaphylaxis defined according to Ring and Messer Classification	From randomisation until 28 days
Bowel Ischemia	Proven by Abdominal CT or endoscopy	From randomisation until 28 days
Cost effectiveness analysis	Actual costs at 28 and 90 days and modelisation for 5 years	28 days, 90 days and 5 years from randomisation

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: University Hospital, Rouen; Centre Hospitalier Universitaire Dijon; University Hospital, Caen; Amiens University Hospital; Centre Hospitalier de Lens; Centre hospitalier de Dunkerque
• Investigators: Principal Investigator: Mouhamed MOUSSA, MD, University Hospital, Lille

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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/cc12681.
• 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;101(2):682-9. doi: 10.1016/j.athoracsur.2015.07.046. Epub 2015 Oct 9.
• 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.
• 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. Erratum In: JAMA. 2014 Nov 19;312(19):2045.
• 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: 10.1097/01.tp.0000437435.19980.8f.
• 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 cohort of cardiac surgery patients: a prospective nested case-control study. Blood. 2011 Apr 21;117(16):4218-25. doi: 10.1182/blood-2010-10-313973. Epub 2011 Feb 16.
• 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 Application and Outcome From the Extracorporeal Life Support Organization (ELSO) Registry. Ann Thorac Surg. 2017 Jul;104(1):62-69. doi: 10.1016/j.athoracsur.2016.10.023. Epub 2017 Jan 26.
• 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.
• 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.
• 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. doi: 10.1136/bmj.h1354.
• 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, Wood EM, Seifried E; ICC PBM Frankfurt 2018 Group. Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference. JAMA. 2019 Mar 12;321(10):983-997. doi: 10.1001/jama.2019.0554.
• 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.
• 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 May;33(5):1216-1220. doi: 10.1053/j.jvca.2018.07.045. Epub 2018 Aug 3.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): September 18, 2025
• Study Completion (Estimated): December 18, 2025

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ECMO; Outcome; Transfusion; ECLS; Refractory cardiogenic shock; ScVO2
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic
• Other Study ID Numbers: 2020_04; 2021-A01925-36 (Other Identifier: ID-RCB number, ANSM); PHRCI-19-032 (Other Identifier: AAP number, DGOS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No