SAN FRANCISCO—The pivotal TRYTON trial failed to meet its primary clinical endpoint, findings that underscore limitations with classical clinical trial criteria, the lead investigator and panelists suggested Oct. 30 at the Transcatheter Cardiovascular Therapeutics (TCT) scientific session in San Francisco.
Despite the disappointing results, the study provides physicians with insights on how to treat patients with large bifurcation coronary lesions, lead investigator Martin Leon, MD, told Cardiovascular Business.
TRYTON is an international, multicenter randomized clinical trial that compared current practice for treating patients with coronary bifurcation lesions with the Tryton stent, a bare-metal bifurcation stent with three components: an 8 mm main branch zone, a 4.5 mm transition zone and a 6.6 mm side branch zone.
The study enrolled 704 patients randomized to either receive provisional stenting with a drug-eluting stent (DES) in the main vessel and a stent in the side branch only if specific criteria were met (349 patients) or the Tryton bifurcation stent with a DES in the main vessel (355 patients). The primary noninferiority endpoint was target vessel failure, a composite of cardiac death, target vessel MI or target vessel revascularization at nine months. The definition of target vessel MI was defined as periprocedural CK-MB elevations of more than three times the norm.
The secondary superiority endpoint was improvement in the percent diameter stenosis in the side branch at nine months.
The bifurcation stent strategy fell short in the primary clinical endpoint; the rate of target vessel failure was 12.8 percent in the standard practice group vs. 17.4 percent in the Tryton stent group. Leon attributed the higher target vessel failure rate in the Tryton group in large part to elevated CK-MB findings.
“This is a dedicated bifurcation stent which means in all these cases a second stent was implanted by intent in the Tryton experimental arm as opposed to the intent of using only a single, main vessel stent in the control arm. Whenever you put in a second stent you will get more CK-MB release,” he said in the interview.
In the secondary endpoint, the Tryton stent strategy prevailed; the percent diameter stenosis was 31.6 in the Tryton stent group vs. 38.6 in the standard practice group.
Researchers also conducted a post hoc analysis focused on the 39 percent of patients who had side branches of more than 2.25 mm. “When you do a post hoc subset analysis of the large bifurcations, then the Tryton stent performed extremely well,” Leon said. In that analysis, the Tryton group had lower target vessel failure, lower periprocedural MIs and slightly better repeat revascularization rates and a greater difference in angiographic outcomes.
By site assessment, 99 percent of participants in the trial had true bifurcations. A Core Lab assessment placed the overall number at 88 percent. “Had we been able to enroll the intended population of patients, the study might have been a positive study,” he said. “But that is post hoc wishful thinking.”
The study design incorporated the FDA’s criteria for determining a target vessel MI, which is three times normal CK-MB. He described the biomarker as an overly sensitive instrument.
Panelists at a press conference commiserated with Leon over the trial’s challenges.
“You have to have events,” said Bernard J. Gersh, MD, ChB, DPhil, of the Mayo Clinic in Rochester, Minn., after Leon explained the FDA requires a clinical endpoint to have a device approved. “But it is frustrating when you are penalized for minor events.” He pointed to data that confirm that periprocedural CK-MB rises with “no prognostic significance, whether you call it three times or five times normal.”
Philippe Genereux, MD, of NewYork-Presbyterian Hospital and Columbia University Medical Center in New York City, said the elevation levels with MI needs to be defined. “We’re still struggling in interventional cardiology with what these periprocedural MIs mean.”
Both strategies proved to be safe, Leon said at the press conference. “There were rare clinically significant MIs and stent thrombosis rates were overall 0.04 percent for this study” and clinically driven target vessel revascularization rates also were low.
Physicians likely will be disappointed in the noninferiority finding, but the data may help inform treatment decisions. “If you have access to this device, if it is a larger side branch then this device may offer