The Collagenase Total Occlusion-1 (CTO-1) Trial: A Phase I, Dose Escalation, Safety Study

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Abstract

Background -

Percutaneous interventions for chronic total occlusions (CTO) have low success rates, primarily due to failure of guidewire crossing. Collagen-rich matrix constitutes the main barrier to CTO crossing. In preclinical studies, local delivery of a bacterial collagenase formulation improved guidewire crossing. The Collagenase Total Occlusion-1 (CTO-1) Trial is a Phase 1, dose escalation trial to assess the safety and efficacy of collagenase therapy to facilitate guidewire crossing in coronary artery chronic occlusions.

Methods and Results -

Twenty subjects, with ≥1 previous failure of CTO guidewire crossing, were enrolled at two sites. Subjects were treated in four distinct cohorts of five patients, with escalation of collagenase dose in each cohort from 300 to 1200 μg. Collagenase was locally delivered into the occlusions using either an over-the-wire balloon (OTW) system (n=8) or finecross microcatheter (n=12) for a period of 30 minutes. Subjects were brought back to the catheterization laboratory for guidewire crossing and angioplasty the following day. Guidewire crossing was successfully achieved in 15 subjects (75%). A soft tip guidewire (Whisper, Pilot-50, Fielder XT) was either the sole or predominant guidewire used in 75% of successful crossings. Non-STEMIs occurred in three patients due to sidebranch ischemia during stenting. Computed tomographic angiography at three months showed no late complications and patent stents in successfully treated CTO. Anginal improvement occurred with a reduction in CCS class from baseline to three months (2.5±0.6 versus 0.9±0.9, p<0.001).

Conclusions -

Local delivery of collagenase into coronary CTO is feasible and safe with encouraging guidewire crossing results in previously failed cases. Larger clinical trials are required to determine efficacy.

Clinical Trial Registration Information:

The CTO-1 trial has been registered on www.clinicaltrials.gov (NCT01271335).

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