Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock

Study Overview
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Brief Summary
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Data from case series and large retrospective trials suggest that the early treatment of cardiogenic shock AMI patients with the association of VA-ECMO and IABP may significantly decrease mortality, which is still unacceptably high nowadays (40-50% at 30 days). An important benefit for the patients randomized to the ECMO arm is expected and the risk-to-benefit ratio is expected to be in favor of the experimental treatment arm.

Detailed Description
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Scientific background - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used more and more frequently in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock despite the absence of high level scientific evidence to recommend the use of temporary circulatory support devices (TCS) in this setting.TCS support may also benefit to cardiogenic shock patients not initially refractory to conventional medical management since their mortality exceeds 40% and most of deaths are due to the development of refractory cardiogenic shock and multiple organ failure. The ANCHOR trial is therefore designed to test the hypothesis that VA-ECMO support associated with IABP results in improved outcomes in comparison with optimal medical treatment alone in patients with AMI and cardiogenic shock. An ethical rescue option to VA-ECMO will however be provided to control patients with cardiogenic shock refractory to conventional medical treatment since recent data suggested survival up-to 50% with ECMO support in this setting. Main objective - To determine if early VA-ECMO combined with IABP support and optimal medical treatment would improve the outcomes of patients with acute myocardial infarction complicated by cardiogenic shock as compared with optimal medical treatment alone. Scope of the study - Patients satisfying all of the Inclusion and Exclusion Criteria will be classified as 'Eligible'. Consent to research will be obtained from a close relative or surrogate for all eligible patients prior to randomization. Should such a person be absent, eligible patients will be randomized according to the specifications of emergency consent and the patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow. Randomization will be possible in centers with robust experience in the management of AMI and cardiogenic shock but no on-site ECMO capability providing that an ECMO retrieval team from the nearest ECMO center can establish ECMO no later than 2 hours after randomization. Before randomization, physicians at the non-ECMO center will check that the ECMO team is immediately available and that an ICU/CCU bed is available at the ECMO center. Thereafter, if the patient is randomized to the ECMO arm, the mobile ECMO retrieval team will travel to the center, initiate VA-ECMO and will rapidly transfer the patient on VA-ECMO to the ECMO center. Description of experimental ECMO + IABP Arm Protocolized conventional management of cardiogenic shock VA-ECMO will be started as soon as possible For patients randomized at non-ECMO centers, a mobile ECMO team will initiate ECMO at the non-ECMO center and transport the patient to the ECMO center immediately IABP inserted in the contralateral femoral artery (unless technically not possible) ECMO management according to protocol ECMO weaning according to protocol Description of conventional treatment Arm Protocolized conventional management of cardiogenic shock IABP not recommended. No other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) permitted Rescue VA-ECMO only if one of 1 or 2 or 3 applies: 1. Refractory cardiogenic shock defined as Cardiac index <1.2 l/min/m² or VTI <6 cm AND Assessment and correction of hypovolemia AND (dobutamine ≥15 microg/kg/min + norepinephrine ≥1.5 microg/kg/min) OR epinephrine ≥ 0.75 microg/kg/min Serum lactate >5 mmol/L or serum lactate increased >50% in the last 6 hours 2. Uncontrolled lethal arrhythmia despite K >4.5 mmol/l AND Mg >1.0 mmol/l AND Intubation and mechanical ventilation with deep sedation AND IV Loading of amiodarone AND IV xylocaine 3. Refractory cardiac arrest Mandatory validation of rescue VA-ECMO by an independent adjudicator.

Official Title
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Assessment of ECMO in Acute Myocardial Infarction With Non-reversible Cardiogenic Shock to Halt Organ Failure and Reduce Mortality (ANCHOR)

Conditions
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Acute Myocardial Infarction, Cardiogenic Shock

Intervention / Treatment
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* Device: VA-ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiogenic shock complicating acute myocardial infarction (STEMI or NSTEMI) Revascularization by PCI for acute myocardial infarction has been performed or is planned in the following 60 minutes Systolic blood pressure <90 mmHg for >30 min or catecholamine support required to maintain systolic blood pressure >90 mmHg Signs of pulmonary congestion Signs of impaired organ perfusion with at least one of the following: Altered mental status OR cold, clammy skin and extremities OR oliguria with urine output <30 ml/h OR serum lactate >2.0 mmol/l Exclusion Criteria: Age <18 years Pregnancy Onset of shock >24 Hours Shock of other cause (hypovolemic, anaphylactic or vagal shock) Shock due to massive pulmonary embolism Resuscitation >30 minutes No intrinsic heart activity Patient moribund on the day of randomization or SAPS II >90 Surgical revascularization for AMI (CABG) planned or already performed prior to randomization Cerebral deficit with fixed dilated pupils or Irreversible neurological pathology Mechanical infarction complication (massive mitral regurgitation, pericardium drainage required, septal ventricular defect) Severe peripheral artery disease or previous aortic or ilio-femoral surgery precluding ECMO and IABP insertion Aortic regurgitation > II Other severe concomitant disease with limited life expectancy < 1 year Proven heparin-induced thrombocytopenia ECMO device not immediately available

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
Interventional Model Description: A multicenter, prospective, randomized, comparative open trial will be conducted on two parallel groups of patients with AMI complicated by cardiogenic shock.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental ECMO + IABP Arm<br>VA-ECMO will be instituted percutaneously under echo guidance via the femoral route as soon as possible. An IABP will be systematically inserted in the contralateral femoral artery (unless technically not possible). | Device: VA-ECMO<br>* The ECMO device will be the CardioHelp (MAQUET, GETINGE, Orléans, France) using the veno-arterial setting and percutaneous femoro-femoral cannulation with MAQUET GETINGE HLS cannulae. Intraortic balloon pump will be MEGA 50 cc or 40cc, (MAQUET, GETINGE, Orléans, France).<br>|
| No Intervention: Control Conventional Treatment Arm<br>Standard management of cardiogenic shock due to myocardial infarction according to the current ESC guidelines. It is not recommended to use IABP support and no other TCS device (e.g., ECMO, Impella, Thoratec PHP, TandemHeart) will be permitted in the control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure at Day 30 | Death in the ECMO group and death OR rescue ECMO in the control group | At day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at Day 30 | All-cause mortality at day 30 | At day 30 | 
| Major Adverse Cardiovascular Events | Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant. | At day 30 | 
| Stroke | Any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI | At day 30 | 
| Recurrent myocardial infarction | Recurrent myocardial infarction | At day 30 | 
| Need for repeat revascularization with PCI and/or CABG | Need for repeat revascularization (PCI and/or CABG) | At day 30 | 
| Need for renal replacement therapy | Need for renal replacement therapy | At day 30 | 
| Re-hospitalization for heart failure | re-hospitalization for heart failure | At day 30 | 
| Escalation to LVAD or total artificial heart | Escalation to permanent left ventricular assist device or total artificial heart | At day 30 | 
| Cardiac transplantation | Cardiac transplantation | At day 30 | 
| Major bleeding | Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d) | At day 30 | 
| Red blood cells transfused | Number of packed red blood cells transfused | At day 30 | 
| Serum lactate | Time to serum lactate normalization | At day 30 | 
| Number of days alive without organ failure at day 30 | Number of days alive without organ failure(s) defined with the SOFA score, catecholamine support, mechanical ventilation and renal replacement therapy | At day 30 | 
| Durations of ICU stay and hospitalization | Durations of ICU stay and of hospitalization | At day 30 | 
| LV function | LV function assessed with Doppler echocardiography or magnetic resonance imaging | At day 30 | 
| NYHA/INTERMACS status | NYHA/INTERMACS status | At day 30 | 
| ECMO-related complications | ECMO-related complications (infection at VA-ECMO cannulation sites requiring antibiotics, hemorrhage, limb ischemia requiring surgery, cannula or circuit thrombosis, overt pulmonary edema, thrombocytopenia, gaseous emboli and hemolysis). | At day 30 | 
| Treatment failure at one year | Treatment failure defined as death (all-cause) in the ECMO group and death (all-cause) OR rescue ECMO in the control group. | At one year | 
| Mortality at one year | All-cause mortality | At one year | 
| Major Adverse Cardiovascular at one year | MACE, Major Adverse Cardiovascular Events are defined as death, stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), recurrent myocardial infarction, need for repeat revascularization (PCI and/or CABG), renal replacement therapy, re-hospitalization for heart failure, escalation to permanent left ventricular assist device (LVAD) or total artificial heart, cardiac transplant. | At one year | 
| Stroke at one year | Stroke (any new neurological symptoms in association with signs of ischemia or hemorrhage in a cranial CT or MRI), | At one year | 
| Recurrent myocardial infarction at one year | Recurrent myocardial infarction between randomization and one year | At one year | 
| PCI and/or CABG at one year | Repeat revascularization (PCI and/or CABG) between randomization and one year | At one year | 
| Renal replacement therapy at one year | Need for renal replacement therapy between randomization and one year | At one year | 
| Re-hospitalization for heart failure | Re-hospitalization for heart failure between randomization and one year | At one year | 
| LVAD at one year | Escalation to permanent left ventricular assist device (LVAD) or total artificial heart | At one year | 
| Cardiac transplant at one year | Cardiac transplantation | At one year | 
| Major bleeding at one year | Major bleeding (TIMI definition): Any intracranial bleeding (excluding microhemorrhages <10 mm evident only on gradient-echo MRI) OR Clinically overt signs of hemorrhage associated with a drop in hemoglobin of ≥5 g/dL or a ≥15% absolute decrease in hematocrit OR Fatal bleeding (bleeding that directly results in death within 7 d) | At one year | 
| NYHA/INTERMACS status at one year | NYHA/INTERMACS status | At one year | 
| Returned to work at one year | Rate of patients who returned to work if previously active | At one year | 
| LV ejection fraction at one year | Latest LV ejection fraction | At one year | 
| Short Form 36 (SF-36) questionnaire at one year | Quality of life assessed using the Short Form 36 (SF-36) Health Survey questionnaire | At one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiogenic shock, VA-ECMO, STEMI, NSTEMI, Intraortic balloon pump