Evaluation of the Efficacy of Early Implantation of a Percutaneous Left Ventricular Assist Devices in Acute Coronary Syndrome Complicated by Cardiogenic Shock Compared to Conventional Therapy: a Prospective, Multicenter, Randomized, Controlled and Open-label Clinical Trial

Study Overview
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Brief Summary
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The ULYSS study is a randomized, multicenter, interventional and prospective open-label clinical trial. It aims to evaluate the efficacy of the addition of an early IMPELLA CP support on top of optimal medical therapy and culprit lesion PCI compared to optimal medical care and culprit PCI in patients with an ACS complicated by a CS. A transthoracic echography is required to exclude some non-inclusion criteria as soon as possible and before randomization. Randomization will be performed after an informed consent is signed by the patient, a family member if he is unable to consent or thanks to the emergent consent procedure if all inclusion criteria are met and there are no non-inclusion criteria. A computer-generated randomization list will be drawn-up using a permuted block design (stratified on center). Each center will have a specific list. Randomization 1:1 to one of the 2 groups In all patients, emergent PCI of the culprit lesion will be performed. Control group: patients will receive IV inotropes associated or not with vasopressors according to the attached protocol and based on the current guidelines (annex 1) (2, 4) in addition to emergent culprit lesion PCI Experimental group: patients will receive IMPELLA CP before PCI on top of conventional therapy based on the same protocol as the control group and emergent culprit PCI

Detailed Description
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Primary end-point The primary endpoint (efficacy endpoint) is defined by a composite endpoint assessed at 1 month: All cause death; Need for ECMO; LVAD device implantation; Heart transplant In case of refractory cardiogenic shock (RCS), the use ECMO should be discussed. IMPELLA CP implant is not allowed in the Control group but for venting when required after ECMO implant. Secondary end-points - Efficacy At hospital discharge and at one year, the same criteria will be assessed: All causes death; Need for ECMO; Need for LVAD device implantation or for heart transplant At hospital discharge , at one month and one year, the investigators also want to assess: Myocardial infarctions Stroke Urgent revascularizations (any unplanned revascularization) CV deaths Procedural success (in-hospital) Renal replacement therapies Left ventricle ejection fraction at 1 and 12 month follow up Quality of life at 1 and 12 months follow up (EQ5D questionnaire). During hospital stay: Durations of catecholamines use Length of initial-hospital stay Length of stay in intensive care units (ICU + CCU) The rate of renal replacement therapies Lactates clearance during the first 24 hours Area under the curve of CK release during the first 2 days Left ventricle ejection fraction at 6 and 12 months follow-up Quality of life at one month an one year (EQ5D questionnaire) Additionally, the investigators will investigated safety and economic criteria of the two strategies. - Safety At discharge, at one month and at one year, the investigators will assess: The rate of serious adverse events (urgent vascular surgery, transfusion, emboli). The rate of BARC bleedings ≥3 The rate of vascular complications requiring medical or surgical care Hemostasis parameters, particularly hemolysis Total number of RBC Systemic emboli Medico-economic the investigators will assess: The cost of IMPELLA CP The total costs of the intervention The EQ5D at baseline and 12 months from PCI (Quality of life through utility health states assessment) One year cost-utility analysis: calculated by an incremental cost-utility ratio in terms of costs per additional quality-adjusted life year (QALY). The rational and methods of the health economic analysis are described in the overall document.

Official Title
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Evaluation of the Efficacy of Early Implantation of a Percutaneous Left Ventricular Assist Devices in Acute Coronary Syndrome Complicated by Cardiogenic Shock Compared to Conventional Therapy: a Prospective, Multicenter, Randomized, Controlled and Open-label Clinical Trial

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Device: IMPELLA CP
* Other: Conventional therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years old; ACS ≤ 24 hours; Cardiogenic shock defined by: At least one criteria of low cardiac output defined by SBP ≤ 90 mmHg or the need to use inotropes/vasopressors in order to obtain SBP> 90 mmHg CI ≤ 2.2L/min/m2 At least one criteria of left overload defined by clinical (killip class ≥ 2), biological (NtproBNP > 900pg/ml or BNP > 400pg/ml), radiological non invasive or invasive hemodynamic evaluation At least one criteria of malperfusion defined by clinical (marbles, oliguria ≤ 0.5ml/min/kg, cold/clammy skin and extremities,..) biological approach (arterial lactate ≥ 2mmol/L, ScVO2 < 60%) Stage C or D of the ACC classification of CS Revascularization by PCI intended after coronary angiography; Lack of significant femoral artery stenosis or other local contra-indication to a 14 Fr sheath; Signed informed consent (patient and/or family/relative) or emergency procedure Subject affiliated to or beneficiary of a social security system. Exclusion Criteria: Persons referred in articles L.1121-5 to L.1121-8 and L.1122-2 of the Public Health Code: Pregnant, parturient or breastfeeding woman Person deprived of liberty for judicial or administrative decision Adult person under legal protection (any form of public guardianship) Onset of shock >24 hours CS not related to ACS Patient with prolonged cardiac arrest (>5 mins) Contra-indications to Impella CP implantations: Isolated right ventricular failure LV thrombus Mechanical aortic valve or heart constrictive device Aortic valve stenosis or calcification (equivalent to an orifice area of 0.6cm2 or less) Moderate to severe aortic insufficiency (echocardiographic assessment graded as ≥ 2) Severe peripheral arterial disease precluding placement of the Impella system Combined cardiorespiratory failure Presence of an Atrial or Ventricular Septal Defect (including post infarctus VSD) Left ventricular rupture Cardiac tamponade Mechanical complication of myocardial infarction Cerebral deficit with fixed dilated pupils or irreversible neurological pathology Anoxic brain injury Active bleeding Contra-indication to antiplatelet or anticoagulant therapy Life expectancy < 1 year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMPELLA CP GROUP<br>patients will receive IMPELLA CP before PCI on top of conventional therapy based on the same protocol as the control group and emergent culprit PCI | Device: IMPELLA CP<br>* Implantation of the IMPELLA CP will be performed using the femoral route in most patients. Echo guided puncture to gain access for IMPELLA CP will be encouraged and a local angiography will be promoted to check the feasibility of device implantation. The implantation will follow gold standard after obtaining an ACT >250 s. As soon as the device is in place it will be started.<br>|
| Active Comparator: CONTROL GROUP<br>patients will receive IV inotropes associated or not with vasopressors according to the attached protocol and based on the current guidelines (annex 1) (2, 4) in addition to emergent culprit lesion PCI | Other: Conventional therapy<br>* The patients will receive up to date management according to the consensus of care regarding inotropes and vasopressors in CS (2,4). A dedicated protocol will ensure that management is similar between centers and in both groups. The shock team will be in charge of all therapeutic decisions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of death from all causes |  | 1MONTHS | 
| The rate of ECMO placements |  | 1months | 
| The rate of implementation of the LVAD device |  | 1 months | 
| The rate of cardiac transplants |  | 1months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of death from all causes |  | 1 year | 
| The rate of ECMO placements |  | 1 year | 
| The rate of implementation of the LVAD device |  | 1 year | 
| The rate of cardiac transplants |  | 1 year |