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

Primary Purpose

Cardiogenic Shock, Extracorporeal Membrane Oxygenation, Transfusion Related Complication

Status
Not yet recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Packed Red Blood Cells (PRBCs)
Sponsored by
University Hospital, Lille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiogenic Shock focused on measuring ECMO, ECLS, Refractory cardiogenic shock, Transfusion, ScVO2, Outcome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universitaire de Lille

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Individulised transfusion strategy group

Conventionnal transfusion strategy group

Arm Description

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

Transfusion will be performed in case of a hemoglobin drop <9 g/dL

Outcomes

Primary Outcome Measures

Number of PRBCs transfused per VA-ECMO day of support
Total number of PRBCs transfused during support adjusted for VA- ECMO duration

Secondary Outcome Measures

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
Total number of PRBCs transfused during the 28-day following cannulation
Total number of PRBCs transfused during the 28-day following cannulation
Changes in hemoglobin levels during VA-ECMO support
daily hemoglobin levels
Changes in ScVO2 levels during VA-ECMO support
daily ScVO2 levels
Changes in vosoactive index score levels during VA-ECMO support
daily vasoactive index score levels
Mortality under ECMO support
All cause mortality before ECMO weaning
90-day Mortality
All cause mortality from cannulation untill 90 days
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)
Duration of mechanical ventilation
Duration of mechnanical ventilation from cannulation untill 28 days
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
Duration of vasoactive support
Duration of vasoactive drug support from cannulation untill 28 days
Hospital lenght of stay
Length of stay from cannulation censored at 90 day
HLA immuno-sensitisation
Proportion of HLA immunosensitisation occuring after cannulation
Proportion of patient with Transfusion related immunologic ( non HLA-related) complications
Transfusion related acute lung injury, hemolytic anemia, irregular antibodies
Proportion of patients with nex onset of sepsis
Sepsis is defined according to Surviving Sepsis Campaign guideline
Proportion of patients with a new onset of acute kidney injury
Acute kidney injury is define according to KDIGO classification
Proportion of patients with liver failure
Liver failure is defined as Hepatic component of SOFA score, Transaminasis Levels
Ischemic stroke
Ischemic stroke is defined as clinical symptoms confirmed by aCT Scan of MRI imaging
Myocardial infarction
According to the Universal definition of myocardial infarction, ESC guidelines
Pulmonary oedema
Dignose by the attending physician based on (Dyspnae, Thoracic X-rays), bowel ischemia ( Abdominal CT or endoscopy proven)
Anaphylactic complications
Anaphylaxis defined according to Ring and Messer Classification
Bowel Ischemia
Proven by Abdominal CT or endoscopy
Cost effectiveness analysis
Actual costs at 28 and 90 days and modelisation for 5 years

Full Information

First Posted
December 21, 2022
Last Updated
January 16, 2023
Sponsor
University Hospital, Lille
Collaborators
Amiens University Hospital, University Hospital, Caen, University Hospital, Rouen, Centre Hospitalier Universitaire Dijon, Centre hospitalier de Dunkerque, Centre Hospitalier de Lens
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1. Study Identification

Unique Protocol Identification Number
NCT05699005
Brief Title
Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 2023 (Anticipated)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
Amiens University Hospital, University Hospital, Caen, University Hospital, Rouen, Centre Hospitalier Universitaire Dijon, Centre hospitalier de Dunkerque, Centre Hospitalier de Lens

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiogenic Shock, Extracorporeal Membrane Oxygenation, Transfusion Related Complication, Anemia, Oxygen Delivery
Keywords
ECMO, ECLS, Refractory cardiogenic shock, Transfusion, ScVO2, Outcome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Patients and datamanagement responsible for statistical analysis will be blinded of the patient allocation group until the study completion
Allocation
Randomized
Enrollment
238 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Individulised transfusion strategy group
Arm Type
Experimental
Arm Description
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
Arm Title
Conventionnal transfusion strategy group
Arm Type
Active Comparator
Arm Description
Transfusion will be performed in case of a hemoglobin drop <9 g/dL
Intervention Type
Drug
Intervention Name(s)
Packed Red Blood Cells (PRBCs)
Other Intervention Name(s)
ScVO2 assesment to guide transfusion
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of PRBCs transfused per VA-ECMO day of support
Description
Total number of PRBCs transfused during support adjusted for VA- ECMO duration
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Secondary Outcome Measure Information:
Title
Number of PRBCs transfused per VA-ECMO day of support in postcardiotomy patients
Description
Total number of PRBCs transfused during support adjusted for VA- ECMO duration in patients that underwent cardiac surgery
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
Total number of PRBCs transfused during the 28-day following cannulation
Description
Total number of PRBCs transfused during the 28-day following cannulation
Time Frame
From randomisation until 28 days
Title
Changes in hemoglobin levels during VA-ECMO support
Description
daily hemoglobin levels
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
Changes in ScVO2 levels during VA-ECMO support
Description
daily ScVO2 levels
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
Changes in vosoactive index score levels during VA-ECMO support
Description
daily vasoactive index score levels
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
Mortality under ECMO support
Description
All cause mortality before ECMO weaning
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
90-day Mortality
Description
All cause mortality from cannulation untill 90 days
Time Frame
90 days from cannulation
Title
ECMO removal modalities
Description
Proportion of patients that according to each reason for removal ( Recovery, heart transplantation, Left ventricle or biventricle assist device or death under support)
Time Frame
From randomisation until VA-ECMO weanning assessed up to 28 days
Title
Duration of mechanical ventilation
Description
Duration of mechnanical ventilation from cannulation untill 28 days
Time Frame
28 days from cannulation
Title
Proportion of patient that received a renal replacement therapy and its duration
Description
Number of patient that underwent a renal replacement therapy and duration of renal replacement therapy from cannulation untill 28 days
Time Frame
28 days from cannulation
Title
Duration of vasoactive support
Description
Duration of vasoactive drug support from cannulation untill 28 days
Time Frame
28 days from cannulation
Title
Hospital lenght of stay
Description
Length of stay from cannulation censored at 90 day
Time Frame
28 days from cannulation
Title
HLA immuno-sensitisation
Description
Proportion of HLA immunosensitisation occuring after cannulation
Time Frame
28 and 90 days from cannulation
Title
Proportion of patient with Transfusion related immunologic ( non HLA-related) complications
Description
Transfusion related acute lung injury, hemolytic anemia, irregular antibodies
Time Frame
From randomisation until 28 days
Title
Proportion of patients with nex onset of sepsis
Description
Sepsis is defined according to Surviving Sepsis Campaign guideline
Time Frame
From randomisation until 28 days
Title
Proportion of patients with a new onset of acute kidney injury
Description
Acute kidney injury is define according to KDIGO classification
Time Frame
From randomisation until 28 days
Title
Proportion of patients with liver failure
Description
Liver failure is defined as Hepatic component of SOFA score, Transaminasis Levels
Time Frame
From randomisation until 28 days
Title
Ischemic stroke
Description
Ischemic stroke is defined as clinical symptoms confirmed by aCT Scan of MRI imaging
Time Frame
From randomisation until 28 days
Title
Myocardial infarction
Description
According to the Universal definition of myocardial infarction, ESC guidelines
Time Frame
From randomisation until 28 days
Title
Pulmonary oedema
Description
Dignose by the attending physician based on (Dyspnae, Thoracic X-rays), bowel ischemia ( Abdominal CT or endoscopy proven)
Time Frame
From randomisation until 28 days
Title
Anaphylactic complications
Description
Anaphylaxis defined according to Ring and Messer Classification
Time Frame
From randomisation until 28 days
Title
Bowel Ischemia
Description
Proven by Abdominal CT or endoscopy
Time Frame
From randomisation until 28 days
Title
Cost effectiveness analysis
Description
Actual costs at 28 and 90 days and modelisation for 5 years
Time Frame
28 days, 90 days and 5 years from randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mouhamed MOUSSA, MD
Phone
0320445962
Email
mouhamed.moussa@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mouhamed MOUSSA, MD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universitaire de Lille
City
Lille
State/Province
Nord
ZIP/Postal Code
59000
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO

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