A Study to Evaluate the Safety and Efficacy of PiCSO in Anterior STEMI Patients (PiCSO-AMI-II)

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.

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).

Study Overview

• Status: Withdrawn
• Conditions: Anterior Wall Myocardial Infarction; STEMI - ST Elevation Myocardial Infarction
• Intervention / Treatment: Device: PiCSO Impulse System

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years old
2. Culprit lesion in proximal or mid left anterior descending artery (LAD)
3. Pre-PCI TIMI flow 0, 1 or 2
4. Symptoms onset time consistent with myocardial ischemia (e.g. persistent chest pain, shortness of breath, nausea/vomiting, fatigue, palpitations or syncope) ≤ 12 h
5. 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
6. Emergent PCI will be performed according to national and local hospital guidelines
7. Consent per approved national IRB/EC specific requirements prior to the procedure.

Exclusion Criteria:

1. Patient transferred from an outside hospital where invasive coronary procedure was attempted (including diagnostic catheterization)
2. Implants or foreign bodies in the coronary sinus
3. Left main disease >= 50%
4. 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.
5. 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
6. Known pregnancy or breastfeeding
7. Known large pericardial effusion or cardiac tamponade
8. Known hemodynamically relevant left to right and right to left shunt
9. Known previous myocardial infraction (MI)
10. Previous coronary artery bypass graft (CABG)
11. 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
12. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), any recent genitourinary (GU) or gastrointestinal (GI) bleed (within 3 months)
13. Administration of fibrinolytic therapy within 24 hours prior to enrollment
14. Cardiogenic shock (systolic blood pressure (SBP) < 90 mmHg), need for mechanical circulatory support, intravenous pressor or pre-randomization intubation
15. Patients with cardio-pulmonary resuscitated (CPR) cardiac arrest for more than 5 min or whom baseline neurologic status is not present
16. Patient not suitable for femoral vein access
17. Contraindication to cardiac magnetic resonance imaging CMR (e.g. claustrophobia, foreign body implants incompatible with CMR, gadolinium intolerance)
18. Active participation in another drug or device investigational study that has not reached its primary endpoint
19. Known severe kidney disease (eGFR <=30 mL/min/1.73 m2 by MDRD formula) or on hemodialysis
20. Chronic obstructive pulmonary disease (COPD) with home oxygen therapy or on chronic steroid therapy
21. Unconscious on presentation
22. Patients under judicial protection, legal guardianship or curatorship
23. 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
24. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; This is the actual control group receiving conventional therapy, ie. percutaneous coronary intervention.
Experimental: PiCSO; 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; 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.

What is the study measuring?

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 treatmentAny 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
ST-segment resolution	ST-segment resolution at 60-90 minutes post flow restoration	60-90 minutes post flow restoration
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
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

Collaborators and Investigators

• Sponsor: Miracor Medical SA
• Investigators: Principal Investigator: Gregg W. Stone, Prof., Mount Sinai, New York, US

Study record dates

Study Major Dates

• Study Start (Anticipated): March 30, 2023
• Primary Completion (Anticipated): July 31, 2025
• Study Completion (Anticipated): June 30, 2028

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: PiCSO; PiCSO Impulse System
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Anterior Wall Myocardial Infarction
• Other Study ID Numbers: MIR-CIP 0003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes