A Study to Evaluate Safety and Feasibility of PiCSO Therapy in Patients With ST Elevation Inferior Wall Myocardial Infarction.

Study Overview
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Brief Summary
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The objective of this study is to assess safety and feasibility of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) therapy in patients with extensive ST elevation inferior wall myocardial infarction presenting with TIMI 0 or 1 and symptom duration ≤ 12 hours undergoing percutaneous coronary intervention (PCI) compared to standard PCI.

Detailed Description
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This is a multicenter, randomized (2 PiCSO :1 Control), controlled, pilot study to evaluate safety and feasibility of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) therapy in patients with extensive ST elevation inferior wall myocardial infarction presenting with TIMI 0 or 1 and symptom duration ≤ 12 hours treated adjunct to percutaneous coronary intervention (PCI) compared to standard PCI. Patients with an ST-segment elevated inferior infarct eligible for PCI will be invited to participate in the PiCSO-AMI-V Inferior 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 for a FU visit at 12-36 hours, 30 days, 6 months and 1 year post index procedure. 12-36 hours and 6 months post index the patient will get a echocardiogram. At every FU visit safety data and health status will be documented.

Official Title
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A Randomized, Controlled, Pilot Study to Evaluate Safety and Feasibility of Pressure-controlled Intermittent Coronary Sinus Occlusion (PiCSO) Therapy in Patients With ST Elevation Inferior Wall Myocardial Infarction Presenting With TIMI 0 or 1 and Symptom Duration ≤ 12 Hours Treated Adjunct to Percutaneous Coronary Intervention (PCI) Compared to Standard PCI.

Conditions
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STEMI - ST Elevation Myocardial Infarction, Inferior 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 Right dominance with culprit lesion in mid or proximal RCA Pre-PCI TIMI flow 0 or 1 in the culprit lesion Symptom onset time consistent with myocardial ischemia (e.g. persistent chest pain, shortness of breath, nausea/vomiting, fatigue, palpitations or syncope) ≤ 12 h ECG evidence of acute inferior myocardial infarction with ST-elevation ≥ 2 mm (0.2 mV) in 2 or more contiguous inferior precordial ECG leads (II, III, AVF) 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 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% Large left anterior descending artery providing blood supply beyond the left ventricular apex (supplying part of the inferior wall) as judged by angiography. Known allergy to polyurethanes, PET or stainless steel, both heparin and bivalirudin, or all of clopidogrel, ticagrelor or prasugrel that cannot be adequately premedicated Known pregnancy or breastfeeding Known large pericardial effusion or cardiac tamponade Known hemodynamically relevant left to right and right to left shunt Previous CABG Known neurologic abnormality such as tumor or 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 GU or GI bleed (within 3 months) Administration of fibrinolytic therapy within 24 hours prior to enrollment Cardiogenic shock (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 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 COPD with home oxygen therapy or on chronic steroid therapy for COPD Unconscious on presentation Patients under judicial protection, legal guardianship or curatorship Patient 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 Any evidence of active infectious disease, or definite or probable COVID-19 diagnosis within the prior 4 weeks.

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, pilot stage study
Masking: Single


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 |
| --- | --- | --- |
| Adverse Device Effect (ADE) rate at 30 days post index procedure | Adverse Device Effect (ADE) rate at 30 days post index procedure | 30 days post MI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A severity index derived as the mean wall motion score within the region of AWM | 1. Changes in left and right ventricular function assed by echocardiogram performed within 12 to 36 hours of index PCI and 6 months post index PCI | 12 to 36 hours and 6 months post MI | 
| Ejection fraction using measured by Simpson's method with 2 apical view | 1. Changes in left and right ventricular function assed by echocardiogram performed within 12 to 36 hours of index PCI and 6 months post index PCI | 12 to 36 hours and 6 months post MI | 
| The absolute size of the region of abnormal wall motion (AWM) | 1. Changes in left and right ventricular function assed by echocardiogram performed within 12 to 36 hours of index PCI and 6 months post index PCI | 12 to 36 hours and 6 months post MI | 
| Percentage of the endocardium involved (%AWM) | 1. Changes in left and right ventricular function assed by echocardiogram performed within 12 to 36 hours of index PCI and 6 months post index PCI | 12 to 36 hours and 6 months post MI | 
| Wall motion score | 1. Changes in left and right ventricular function assed by echocardiogram performed within 12 to 36 hours of index PCI and 6 months post index PCI | 12 to 36 hours and 6 months post MI | 
| hs-Troponin | Maximum and AUC of hs-Troponin | hospital admission, 6h, 12h, 24h and then daily until day 5 after PCI or discharge | 
| C-reactive protein | Maximum, AUC and velocity of C-reactive protein | hospital admission, 6h, 12h, 24h and then daily until day 5 after PCI or discharge | 
| CK-MB | Maximum and AUC of CK-MB | hospital admission, 6h, 12h, 24h and then daily until day 5 after PCI or discharge | 
| Blushing index | Blushing index at the end of the procedure | Immediately after treatment | 
| 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 presented as % of subjects | Device and Procedural success, assessed as percent of subjects with successful access, delivery, and retrieval of the device and its delivery system | 1 day | 

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