Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO

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

Overview

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

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.

Interventions

• 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

Primary outcome measures

• Number of PRBCs transfused per VA-ECMO day of support [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]

Secondary outcome measures (12)

• Number of PRBCs transfused per VA-ECMO day of support in postcardiotomy patients [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• Total number of PRBCs transfused during the 28-day following cannulation [Time frame: From randomisation until 28 days]
• Changes in hemoglobin levels during VA-ECMO support [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• Changes in ScVO2 levels during VA-ECMO support [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• Changes in vosoactive index score levels during VA-ECMO support [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• Mortality under ECMO support [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• 90-day Mortality [Time frame: 90 days from cannulation]
• ECMO removal modalities [Time frame: From randomisation until VA-ECMO weanning assessed up to 28 days]
• Duration of mechanical ventilation [Time frame: 28 days from cannulation]
• Proportion of patient that received a renal replacement therapy and its duration [Time frame: 28 days from cannulation]
• Duration of vasoactive support [Time frame: 28 days from cannulation]
• Hospital lenght of stay [Time frame: 28 days from cannulation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

France · 1 center

• Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universit — Lille

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 PMID 29130845
• 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. PMID 34862002
• 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. PMID 20236457
• 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. PMID 23594433
• 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. PMID 26443879
• 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. PMID 26836806
• 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. PMID 24691607
• 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. PMID 24300013

Identifiers

NCT: NCT05699005 · 2020_04 · 2021-A01925-36 · PHRCI-19-032

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗