Novel Method of Softening Hard CTO Plaque May Ease Procedural Difficulties

WASHINGTON, DC—For chronic total occlusions (CTOs) that are difficult to treat, a novel approach of injecting an enzyme that breaks down much of the lesion before attempting angioplasty may prove useful in increasing procedural success, according to phase II trial data.

Presenting findings from the TOSCA-5 trial at TCT 2016, Christopher Buller, MD (St. Michael’s Hospital, Toronto, Canada), explained how pretreating CTO patients with collagenase, produced by the bacterium Clostridium histolyticum, can potentially soften the hard plaque in these lesions, especially at the proximal fibrous cap. This is because collagen is one of the main components of CTOs.

Prior animal and first-in-human experience have shown feasibility and safety “with encouraging guidewire crossing results in previously failed cases,” Buller said.

In this study, 75 CTO patients with prior documented failed PCI were randomized to placebo control or either 900 µg or 1,200 µg microcatheter injection of collagenase the day before they underwent antegrade CTO PCI. While there were no significant differences in guidewire crossing success among the groups, operators were numerically more likely to achieve this in a patient who received collagenase in either dose, Buller noted. And while patients in the study arm were also more likely to have a successful soft wire crossing, all patients had similar rates of successful PCI on QCA.
 

Efficacy Results

 

 

Placebo

900 µg

1,200 µg

P Value

Treatment of CTO

Guidewire Crossing

64%

73%

74%

NS

Soft Wire Crossing

0

17%

29%

0.03

Successful PCI by QCA

64%

60%

65%

NS

PCI Procedural Efficiency

Fluoroscopy Time to Cross, min

17.1

16.7

17.3

NS

Total Fluoroscopy Time, min

36.6

34.7

44.6

NS

Radiation, Gy

2.1

2.8

2.5

NS

Contrast during PCI, mL

244

268

339

NS

Total stented length, mm

68

70

74

NS

 

 

 

 

 

 

 

 

 

 

 

 

 

As for safety, there were no instances of MACE at 30 days in either of the study arms, and there was one MI in the placebo group. Periprocedural myonecrosis occurred in two patients in the placebo arm, two in the 900 µg arm, and four in the 1,200 µg arm—all associated with side branch occlusion or perforation.

Pretreatment with collagenase “appears to enable antegrade soft wire crossing of chronic total occlusions,” Buller concluded. “The safety profile of this therapy appears favorable with low rates of adverse events both immediately following administration and at subsequent PCI. The data support development of a pivotal trial.”

Future questions that need to be answered relate to identifying the optimal dose of collagenase and defining the ideal lesion subset for this agent, he added.

‘Obviously Preliminary’ Findings

Speaking to the media, Ori Ben-Yehuda, MD (Cardiovascular Research Foundation, New York, NY), said Buller’s approach was a “very interesting idea,” but that the findings are “obviously preliminary.”

D. Christopher Metzger, MD (Wellmont CVA Heart Institute, Kingsport, TN), also speaking in the press conference, pointed to the “strikingly longer” procedural time observed in patients who received the higher dose of collagenase.

Buller attributed some of this to play of chance, but he noted that “more than the half the procedure is after wiring. So as you increase your wiring success, you obligate yourself to doing a lot more angioplasty down the road. So there's a paradox here as well.”

Lastly, William Gray, MD (Main Line Health/Lankenau Heart Institute, Wynnewood, PA), highlighted a potential safety dilemma of what would happen if the injected collagenase travelled outside the CTO cap. Buller responded, however, that “there were no angiographic adverse events outside the cap.”

Sources
  • Buller CE. TOSCA-5: A prospective, randomized trial evaluating collagenase infusion in patients with coronary artery chronic total occlusions. Presented at: TCT 2016. November 2, 2016. Washington, DC.

Disclosures
  • Buller reports receiving grant/research support from Matrizyme Pharma and consultant fees/honoraria from Abbott Vascular and Volcano as well as holding equity in Soundbit Medical and intellectual property rights in Vascular Solutions.
  • Ben-Yehuda reports receiving consultant fees/honoraria from Abbott Vascular.
  • Metzger reports receiving consultant fees/honoraria from Abbott Vascular, Bard Medical, Boston Scientific, Endologix, and CSI.
  • Gray reports receiving grant/research support from intact vascular and WL Gore & Associates; consultant fees/honoraria from Boston Scientific, Abbott Vascular, Medtronic, Shockwave, and Cook Medical; and other financial support from BioCardia, Contegol, and Silk Road.

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