Microvascular Obstruction Diagnosis Using the CoFI™ System Assessment - II

A prospective, multicenter, international single-arm, pivotal clinical study designed to validate the performance of the CoFI system in detecting MVO in STEMI subjects, as confirmed by CMRI. The study will be conducted in accordance with the Declaration of Helsinki, EN ISO 14155:2020, local and national regulations. Each study site will receive support from a sponsor-certified proctor during the learning curve to ensure consistent and accurate application of the CoFI system.

Microvascular obstruction (MVO) is a common complication that occurs after establishing coronary vessel patency by percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI). Despite the successful restoration of vessel patency through PCI, 50% to 70% of STEMI subjects experience MVO, which affects vessels in the myocardial microcirculation. MVO occurs most commonly in the setting of AMI because the prolonged ischemia leads to endothelial damage, myocyte oedema and microvascular dysfunction. Research has shown that MVO increases the risk of poor clinical outcomes, including death, re-infarction, reduced left ventricular ejection fraction (LVEF), left ventricular (LV) remodeling, heart failure, and more. Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMRI) is the current state-of-the-art for MVO identification and quantification. However, due to clinical reasons, CMRI imaging cannot be performed during the subject's emergent state. In most cases, this means that the diagnosis is made outside the biological window where MVO-related damage to heart muscle could be reversed or at least reduced. Thus, although CMRI is the most accurate method to diagnose MVO, its use in routine practice is limited. Therefore, a direct and accurate quantitative diagnosis during primary PCI is required for early risk stratification in routine clinical practice. The Controlled Flow Infusion (CoFI) system is designed to be integrated into current PCI protocols, enabling the rapid and safe detection of MVO after successful PCI procedures. Using a proprietary algorithm, the system can provide an output for diagnosing microvascular obstruction (MVO) immediately post-PCI by measuring real-time distal coronary back-pressure response to a dynamic infusion sequence downstream of a low-pressure occlusion balloon. The aim of the study is to validate the diagnostic performance of the CoFI system in detecting MVO in anterior STEMI subjects following PPCI as measured in CMRI 1-3 days post-procedure. The study has two phases 1 \& 2. Phase 1 aims to demonstrate whether the pCoFI threshold for MVO detection gathered in the US population aligns with the 95% confidence interval (CI) of the pCoFI threshold from the EU population gathered in the FIH MOCA-I study. Phase 2 has two possible routes, A or B. Depending on the outcome of phase 1, the study will continue along either route. The study progresses into pivotal route A if the threshold 95% CI aligns as described above and into route B if it does not. If the study follows route B the threshold will be reset and the sample size recalculated. In case of route B phase 1 data will become part of the data training set, whereas in route A would phase 1 data will be included in the study analysis set. With a need to follow Route B, comes a substantial clinical investigation plan (CIP) amendment/supplement submission to the FDA and applicable IRBs, before restarting the study. The sample size for the MOCA-II feasibility and pivotal phases will be based on a conservative assumed disease prevalence of 50% MVO+. Interim Analysis An interim analysis is planned to be done after 50% of the subjects have been enrolled to verify if the study's success or futility criteria are met. Based on the interim analysis, the sample size for the primary endpoint may be adjusted according to the actual MVO prevalence from the study data set, as defined by CMRI at 1 to 3 days post-PPCI. The observed prevalence and interim estimates of sensitivity and specificity will be used to reassess the required sample size if the interim study data do not justify an early stop for success.