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

Percutaneous interventions for chronic total occlusions have low success rates, primarily because of failure of guide wire crossing. Collagen-rich matrix constitutes the main barrier to chronic total occlusion crossing. In preclinical studies, local delivery of a bacterial collagenase formulation im...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2012-01, Vol.125 (3), p.522-528
Main Authors: STRAUSS, Bradley H, OSHEROV, Azriel B, RADHAKRISHNAN, Sam, JOHN MANCINI, G. B, MANNERS, Allison, SPARKES, John D, CHISHOLM, Robert J
Format: Article
Language:English
Subjects:
Adult
Aged
Angioplasty, Balloon, Coronary - methods
Bacterial Proteins - administration & dosage
Bacterial Proteins - adverse effects
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular system
Chronic Disease
Collagenases - administration & dosage
Collagenases - adverse effects
Combined Modality Therapy
Coronary Angiography
Coronary Occlusion - diagnostic imaging
Coronary Occlusion - drug therapy
Coronary Occlusion - therapy
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Dose-Response Relationship, Drug
Feasibility Studies
Humans
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Prospective Studies
Treatment Outcome
Vasodilator agents. Cerebral vasodilators
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Summary:Percutaneous interventions for chronic total occlusions have low success rates, primarily because of failure of guide wire crossing. Collagen-rich matrix constitutes the main barrier to chronic total occlusion crossing. In preclinical studies, local delivery of a bacterial collagenase formulation improved guide wire crossing. The Collagenase Total Occlusion-1 (CTO-1) Trial is a phase I, dose-escalation trial to assess the safety and efficacy of collagenase therapy to facilitate guide wire crossing in coronary artery chronic occlusions. Twenty subjects with ≥1 previous failure of chronic total occlusion guide wire crossing were enrolled at 2 sites. Subjects were treated in 4 distinct cohorts of 5 patients, with escalation of collagenase dose in each cohort from 300 to 1200 μg. Collagenase was locally delivered into the occlusions with either an over-the-wire balloon system (n=8) or a fine-cross microcatheter (n=12) for a period of 30 minutes. Subjects were brought back to the catheterization laboratory for guide wire crossing and angioplasty the next day. Guide wire crossing was successfully achieved in 15 subjects (75%). A soft-tip guide wire (Whisper, Pilot-50, Fielder XT) was either the sole or predominant guide wire used in 75% of successful crossings. Non-ST-segment-elevation myocardial infarctions occurred in 3 patients as a result of side-branch ischemia during stenting. Computed tomographic angiography at 3 months showed no late complications and patent stents in successfully treated chronic total occlusion. Anginal improvement occurred with a reduction in Canadian Cardiovascular Society class from baseline to 3 months (2.5±0.6 versus 0.9±0.9; P
ISSN:0009-7322
1524-4539
DOI:10.1161/CIRCULATIONAHA.111.063198