Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Packed Red Blood Cells (PRBCs)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individulised transfusion strategy group<br>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)<br>* 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.<br>* Other names: ScVO2 assesment to guide transfusion;|
| Active Comparator: Conventionnal transfusion strategy group<br>Transfusion will be performed in case of a hemoglobin drop <9 g/dL | Drug: Packed Red Blood Cells (PRBCs)<br>* 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.<br>* Other names: ScVO2 assesment to guide transfusion;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, ECLS, Refractory cardiogenic shock, Transfusion, ScVO2, Outcome