Collagenase Total Occlusion-1 (CTO-1) trial: a phase I, dose-escalation, safety study

Area of Science:

• Cardiovascular Medicine
• Interventional Cardiology
• Biochemistry

Background:

• Percutaneous coronary interventions for chronic total occlusions (CTO) face challenges due to low success rates, primarily from guide wire crossing failures.
• The collagen-rich matrix of CTOs presents a significant barrier to crossing.
• Preclinical data suggested bacterial collagenase could enhance guide wire crossing.

Purpose of the Study:

• To assess the safety and efficacy of locally delivered collagenase in facilitating guide wire crossing in coronary artery chronic total occlusions.
• To evaluate collagenase as a therapeutic agent in the Collagenase Total Occlusion-1 (CTO-1) Trial, a phase I dose-escalation study.

Main Methods:

• Twenty subjects with prior failed CTO guide wire crossing attempts were enrolled.
• Subjects were divided into four cohorts, escalating collagenase dose from 300 to 1200 µg.
• Collagenase was delivered locally via an over-the-wire balloon or microcatheter over 30 minutes, followed by attempted guide wire crossing the next day.

Main Results:

• Successful guide wire crossing was achieved in 75% (15/20) of subjects.
• Soft-tip guide wires were predominantly used in successful crossings.
• Three patients experienced non-ST-segment-elevation myocardial infarctions due to side-branch ischemia during stenting.
• Anginal symptoms significantly improved post-procedure (p<0.001).

Conclusions:

• Local collagenase delivery is a feasible and safe method for coronary CTOs.
• The therapy showed encouraging results for guide wire crossing in previously challenging cases.
• Larger clinical trials are warranted to confirm efficacy.