A Study to Evaluate the Safety and Efficacy of PiCSO in Anterior STEMI Patients

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and efficacy of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) as adjunct to percutaneous coronary intervention (PCI) compared to PCI in the setting of acute anterior ST-segment elevation myocardial infarction (STEMI).

Detailed Description
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This is a multicenter, randomized (2 PiCSO :1 Control), controlled, pivotal study to evaluate safety and feasibility of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) therapy in patients with acute anterior ST-segment elevation myocardial infarction (STEMI), presenting with thrombolysis in myocardial infarction (TIMI) 0, 1, or 2 and symptom duration ≤ 12 hours treated adjunct to PCI compared to standard PCI. Patients with an ST-segment elevated anterior infarct eligible for PCI will be invited to participate in the PiCSO-AMI-II anterior STEMI study. After consent as per approved ethics committee requirements, baseline assessments will be performed. PCI of the culprit vessel should be performed per standard practices. After TIMI flow restoration, the subjects meeting all eligibility criteria will be enrolled into the study and randomized either to PiCSO Group or Control Group. If the subject is randomized to PiCSO Group, the coronary sinus (CS) will be cannulated through the femoral vein and the PiCSO Impulse Catheter will be placed in the CS. In the event the PiCSO Impulse Catheter cannot be placed in the CS within 30 minutes, the physician should proceed with the regular PCI and the PiCSO treatment will be considered a failure. Once PiCSO Impulse Catheter is placed into CS, PiCSO treatment is started followed by stenting. The physician shall target a PiCSO treatment of 45 minutes whereas the treatment should be continued during and post stent insertion. At the end of the PiCSO treatment, the PiCSO Impulse Console is stopped and the PiCSO Impulse Catheter is removed. The patient is seen at 5 days and 6 months for cardiovascular magnetic resonance imaging (CMR). Follow-up visits will take place at day 5, day 30, 6 months, 1 year, 2 years and 3 years. At every follow-up visit safety data and health status will be documented.

Official Title
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A Randomized Controlled Study to Evaluate the Safety and Efficacy of Pressure-controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Anterior STEMI Patients With TIMI 0-2 at Presentation.

Conditions
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STEMI - ST Elevation Myocardial Infarction, Anterior Wall Myocardial Infarction

Intervention / Treatment
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* Device: PiCSO Impulse System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Culprit lesion in proximal or mid left anterior descending artery (LAD) Pre-PCI TIMI flow 0, 1 or 2 Symptoms onset time consistent with myocardial ischemia (e.g. persistent chest pain, shortness of breath, nausea/vomiting, fatigue, palpitations or syncope) ≤ 12 h Electrocardiogram (ECG) evidence of acute anterior myocardial infarction with ST-elevation ≥ 2 mm (0.2 mV) in 2 or more contiguous anterior precordial ECG leads (one of which should be V2, V3, or V4) in men or ≥ 1.5 mm (0.15 mV) in women Emergent PCI will be performed according to national and local hospital guidelines Consent per approved national IRB/EC specific requirements prior to the procedure. Exclusion Criteria: Patient transferred from an outside hospital where invasive coronary procedure was attempted (including diagnostic catheterization) Implants or foreign bodies in the coronary sinus Left main disease >= 50% Need for treatment of any vessel other than the LAD (or its branches) during the index procedure or before the 5 ± 2 days study CMR. Known allergy to polyurethanes, polyethylene terephthalate (PET) or stainless steel, both heparin and bivalirudin, or all of clopidogrel, ticagrelor or prasugrel that cannot be adequately pre-medicated Known pregnancy or breastfeeding Known large pericardial effusion or cardiac tamponade Known hemodynamically relevant left to right and right to left shunt Known previous myocardial infraction (MI) Previous coronary artery bypass graft (CABG) Known neurologic abnormality such as tumor or arteriovenous (AV) malformation, history of stroke within 6 months, any prior intracranial bleed or any permanent neurologic defect History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), any recent genitourinary (GU) or gastrointestinal (GI) bleed (within 3 months) Administration of fibrinolytic therapy within 24 hours prior to enrollment Cardiogenic shock (systolic blood pressure (SBP) < 90 mmHg), need for mechanical circulatory support, intravenous pressor or pre-randomization intubation Patients with cardio-pulmonary resuscitated (CPR) cardiac arrest for more than 5 min or whom baseline neurologic status is not present Patient not suitable for femoral vein access Contraindication to cardiac magnetic resonance imaging CMR (e.g. claustrophobia, foreign body implants incompatible with CMR, gadolinium intolerance) Active participation in another drug or device investigational study that has not reached its primary endpoint Known severe kidney disease (eGFR <=30 mL/min/1.73 m2 by MDRD formula) or on hemodialysis Chronic obstructive pulmonary disease (COPD) with home oxygen therapy or on chronic steroid therapy Unconscious on presentation Patients under judicial protection, legal guardianship or curatorship Subject has other medical illness (e.g., cancer, dementia) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause non-compliance with the protocol, confound the data interpretation, or is associated with limited life expectancy of less than 1 year Patients with definite or probable COVID-19 diagnosis > 4 weeks prior to the current MI unless they had returned to their baseline state of health after recovery from the COVID-19 illness

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: Prospective, multicenter, randomized, controlled, parallel-groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>This is the actual control group receiving conventional therapy, ie. percutaneous coronary intervention. | |
| Experimental: PiCSO<br>This arm will be treated with Pressure controlled intermittent Coronary Sinus Occlusion (PiCSO) in addition to conventional therapy (percutaneous coronary intervention). | Device: PiCSO Impulse System<br>* After blood flow restoration, the subjects meeting all eligibility criteria will be enrolled into the study and randomized either to PiCSO Group or Control Group. If the subject is randomized to PiCSO Group, the coronary sinus (CS) will be cannulated through the femoral vein and the PiCSO Impulse Catheter will be placed in the CS. Once PiCSO Impulse Catheter is placed into CS, PiCSO treatment is started followed by stenting. The physician shall target a PiCSO treatment of 45 minutes whereas the treatment should be continued during and post stent insertion. At the end of the PiCSO treatment, the PiCSO Impulse Console is stopped and the PiCSO Impulse Catheter is removed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12% performance goal rate of PiCSO device or PiCSO procedure related adverse events reported through 30 days | Primary safety endpoint is based on a 12% performance goal rate of PiCSO device or PiCSO procedure related adverse events reported through 30 days post treatment in patients randomized to PiCSO Group in which the PiCSO treatment was delivered or attempted to be delivered. These events will consist of the composite of: Femoral venous access site complications: Major bleed (BARC 3-5) Infections requiring systemic (oral or intravenous) antibiotic treatment Any femoral access site-related events requiring surgery Coronary sinus dissection requiring percutaneous intervention or surgery Pericardial effusion or tamponade requiring percutaneous intervention or surgery Embolization or Thrombosis Stroke | 30 days post index PCI | 
| Difference in myocardial infarct size | Difference in myocardial infarct size (extent of myocardial necrosis quantified by delayed gadolinium enhancement presented as a percentage of left ventricular (LV) mass) between the PiCSO Group and the Control Group, assessed by CMR at 5±2 days post index PCI. | 5 days post index PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Event (MACE) at 30 days as well as 1, 2 and 3 years post index PCI | MACE at 30 days as well as 1, 2 and 3 years post index PCI Cardiovascular death Cardiovascular hospitalization Heart failure (HF) hospitalization New onset or worsening HF | 30 days, 1, 2 and 3 years post index PCI | 
| Individual components of the MACE | Individual components of the MACE to be evaluated at 30 days as well as 6 months and 1, 2 and 3 years post index PCI | 30 days, 1, 2 and 3 years post index PCI | 
| Classification of all-cause death | Classification of all-cause death at 30 days as well as 6 months and 1, 2 and 3 years post index PCI into the following categories: Cardiac cause of death Non-cardiac cause of death Death of Undetermined Cause | 30 days, 6 months, 1, 2 and 3 years post index PCI | 
| Time to death and heart failure hospitalization | The hierarchical composite of time to death within 1 year, time to heart failure hospitalization within one 1-year and infarct size at assessed by CMR at 5±2 days post index PCI. | 1 year post index PCI | 
| Myocardial infarct size (% of LV mass) assessed by CMR at 6 months post index PCI | Myocardial infarct size (% of LV mass) assessed by CMR at 6 months post index PCI | 6 months post index PCI | 
| Occurrence and extent of microvascular obstruction and hemorrhage | Occurrence and extent of microvascular obstruction (MVO, % of LV mass) and hemorrhage assessed by CMR at 5 days post index PCI | 5 days post index PCI | 
| Myocardial function (LVEF, LVESV, LVEDV) | Myocardial function (Left ventricular ejection fraction (LVEF), Left ventricular end-diastolic volume (LVEDV) and Left ventricular end-systolic volume (LVESV)) assessed by CMR at 5 days and 6 months post index PCI | 5 days and 6 months post index PCI | 
| Myocardial Salvage Index and myocardial infarct size | Myocardial Salvage Index at 5 days and 6 months post index PCI (derived from Area at Risk (AAR) assessed by CMR at 5 days and myocardial infarct size (% of LV mass) assessed by CMR at 5 days or 6 months, respectively) | 5 days and 6 months post index PCI | 
| ST-segment resolution | ST-segment resolution at 60-90 minutes post flow restoration | 60-90 minutes post flow restoration | 
| Device success and procedural success rate | Device success and procedural success rate presented as % of subjects | Baseline (treatment day) | 
| Changes in quality of life | Changes in quality of life measured by EQ-5D at 5 days, 6 months and 1, 2, 3 years post index PCI | 30 days, 6 months and 1, 2, 3 years post index PCI | 
| Utilization of health resources | Assess health economics by collecting the utilization of health resources throughout the study duration | 30 days, 6 months and 1, 2, 3 years post index PCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PiCSO Impulse System, PiCSO