Unique Approach Helps Breach Chronic Total Occlusions in FIM Trial

PARIS, France—A novel, enzymatic approach can facilitate the guidewire crossing of difficult-to-treat chronic total occlusions (CTOs), according to late-breaking results from a first-in-man trial reported Wednesday, May 18 at EuroPCR 2011.

Because collagen represents the major constituent of CTOs, particularly at the proximal fibrous cap, researchers led by Bradley H. Strauss, MD, PhD, of Sunnybrook Health Sciences Centre (Toronto, Canada), theorized that pretreatment with the enzyme collagenase could potentially soften the hard plaque in CTO lesions, thereby allowing clinicians to more easily accomplish guidewire crossing. Collagenase, produced by the bacterium Clostridium histolyticum, naturally breaks down human collagen.

For the CTO-1 (Collagenase Total Occlusion-1) study, researchers led by Dr. Strauss studied 20 patients with CTOs that had all undergone previous failed attempts at guidewire crossing. The patients were given increasing doses (300-1,200 µg) of collagenase via intracoronary injection through a finecross microcatheter over a 15-minute period. PCI was attempted the following day, with CT angiographic follow-up at 3 months.

Successful Crossing, Few Complications

The patients all had considerable comorbidities, with Canadian Cardiovascular Society (CCS) class II/III angina and mean lesion length of 19.2 mm. Sixteen of the 20 CTO lesions were successfully crossed and stented, 75% primarily with soft guidewires. In 8 cases (50%), soft guidewires were the only wires needed, while in 4 cases (25%) a stiff wire was used only to cross the distal cap, and in the remaining 4, a stiff wire was used as the primary wire for crossing.

The average procedure time needed to cross the lesion was 47 minutes, with a total fluoroscopy time of 56 minutes and a fluoroscopy time for wire crossing of 21 minutes. Contrast volume for the procedure was 441 mL.

There was one small (< 1 cm) pericardial effusion during the procedure, and 3 NSTEMIs due to side branch ischemia. Anginal improvement was noted in all cases, with a decrease in CCS class from 2.45 to 1.05 (P < 0.001). On angiographic follow-up (available in 19 patients), all stented arteries were patent at 3 months with no myocardial or pericardial changes. There was 1 stenosis that required additional stenting at 6 months.

“I’m very excited and feel that we can certainly deliver collagenase locally into these lesions, and it is safe,” Dr. Strauss said. “The initial results in human coronary CTO lesions suggest that collagenase can facilitate guidewire crossing, in particular with softer guidewires, and may be a useful adjunct to the antegrade approach for percutaneous revascularization.”

High Praise

Dr. Bradley’s presentation drew praise from panelists at the session, in particular renowned inventor John B. Simpson, PhD, MD, of Stanford University (Stanford, CA).

“Thirty years ago, a cardiologist told me that collagenase would be really important in treating coronary disease, and I told him he was crazy, so 30 years later you’re confirming that in fact I was wrong,” he said. “I’m really impressed that [collagenase] might have some application here.”

Lingering Skepticism

Many of the panelists, though, focused on 1 area of concern: how the collagenase could stay localized in the area after injection despite the displacing motion of the surrounding coronary flow.

Dr. Strauss explained that “the advantage of using the finecross is that you can position the catheter within the CTO. So by embedding it in the occlusion and injecting it very softly and then leaving it there for 15 minutes, I think it’s not washed out very quickly.”

He added that the injection is performed by hand to make sure the catheter is engaged in the lesion. “You just have to inject a few drops at a time, very slowly and gently,” Dr. Strauss said.

Some, though, such as Alain Cribier, MD, of Hôpital Charles Nicolle (Rouen, France), were not convinced. “I must say I am still a little skeptical. I don’t understand the way it works. You are injecting the drug for 15 minutes on day 1, and you’re expecting the drug to stay in place?” he said. “There is flow around the area, so the drug is not supposed to stay in place at the level of the lesion.”

“First of all,” Dr. Strauss responded, “I believe the collagenase is taken up locally by the tissue where you’re injecting, so once you get the injection in the right place, I think it’s pretty much trapped within the CTO when you do it. Once the collagenase is trapped inside the lesion, the actual degradation of the collagen will occur over several hours.”

 

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Source:
Strauss BH. CTO-1 collagenase total occlusion first-in-man clinical trial. Presented at: EuroPCR; May 18, 2011; Paris, France.

 

Disclosures:

• Dr. Strauss reports having an ownership stake in and having founded Matrizyme Pharma and having intellectual property rights in collagenase for CTO.

 

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