Collagenase to facilitate guidewire crossing in chronic total occlusion PCI-The Total Occlusion Study in Coronary Arteries-5 (TOSCA-5) trial.

ABSTRACT

BACKGROUND: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO. AIMS: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty. METHODS: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 µg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 µg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only. RESULTS: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 µg, and 29% in 1200 µg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups. CONCLUSION: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent.