Miracor Medical has announced the approval of an investigational device exemption (IDE) from the US Food and Drug Administration (FDA), enabling the company to initiate a pivotal study with its Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) technology.
The PiCSO-AMI-II multicentre, randomised trial will enrol 300 patients with anterior ST-segment elevation myocardial infarction (STEMI) presenting with thrombolysis in myocardial infarction (TIMI) flow 0, 1, and 2 within 12 hours of symptom onset. The primary efficacy endpoint of the study will be infarct size measured by cardiac magnetic resonance imaging (CMR) at five days. The primary safety endpoint is a performance goal for device and procedure related adverse events at 30 days. Major adverse cardiac events and heart failure endpoints will be captured acutely and for up to three years.
PiCSO-AMI-II will be the second major randomised trial to evaluate the role of PiCSO in improving coronary microvascular function and reducing infarct size in patients presenting with anterior STEMI. Miracor is currently recruiting 144 patients in PiCSO-AMI-I, a landmark European randomised controlled trial, with comparable endpoints as the approved US trial. Recruitment in the European study is expected to end this summer. It is anticipated that a future patient-level pooled meta-analysis of the two studies will demonstrate a hard clinical endpoint improvement in heart failure hospitalisation.
PiCSO is used as an adjunctive procedure after epicardial flow has been restored during the primary percutaneous coronary intervention (PCI) procedure. The unique mechanism of action, of intermittently occluding the coronary sinus outflow, redistributes venous blood-flow to the peri-infarct zone and enhances the coronary microcirculation viability by washing-out debris and other noxious agents of the infarct process.
Early non-randomised European studies have suggested that this leads to reduced incidence of coronary microvascular obstruction (MVO) and smaller infarct size, which are both strongly correlated to improvement in heart failure hospitalisations and reduced mortality following primary PCI. Despite improvements in patient care pathways, widespread use of reperfusion strategies, and adjuvant pharmacological therapies, the one-year mortality rate after STEMI in high-risk patients has plateaued over the past decade at 14%. Also, heart failure development after hospital discharge is very prevalent, being diagnosed in approximately 13% of patients at 30 days and 20–30% at one year after discharge.
“Reducing infarct size and MVO is a key factor in improving survival and reducing the risk of heart failure among patients with heart attack. PiCSO therapy is a promising new therapy to reduce infarct size and improve outcomes in anterior STEMI patients. The FDA-approved randomised IDE trial has been designed to validate the safety and effectiveness of PiCSO,” said Gregg W Stone (Mount Sinai Heart Health System, New York, USA) who will be study principal investigator, with Marco Valgimigli (Istituto Cardiocentro Ticino, Lugano, Switzerland) as the study co-principal investigator.
The PiCSO Impulse system received breakthrough designation from the FDA in 2019 and the CE mark in 2020. The development of Miracor’s PiCSO technology is supported by a reimbursable cash advance from the Walloon Region since August 2017.