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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P150039 / PAS001 |
| Date Original Protocol Accepted |
02/21/2017
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| Date Current Protocol Accepted |
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| Study Name |
TRYTON Side Branch Stent PIVOTAL RCT
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| Device Name |
TRYTON SIDE BRANCH STENT
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent Control
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
TRYTON Pivotal Randomized Controlled Trial (RCT) - a prospective, multicenter, single blind controlled study. Subjects were randomized 1:1 to the TRYTON Side Branch Stent with main branch approved DES or side branch balloon angioplasty (POBA) and main branch approved DES for treatment of native coronary artery bifurcation disease.
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| Study Population |
N = 769
704 Randomized (355 TRYTON, 349 POBA)
65 Roll-In (TRYTON)
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| Sample Size |
664 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA
318 subjects randomized 1:1 to DES+TRYTON vs. DES+POBA
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| Key Study Endpoints |
Primary endpoint: Target vessel failure [TVF, a composite of cardiac death, target vessel MI, and target vessel revascularization (TVR) involving the main branch or side branch] at 9 months
Powered secondary angiographic endpoint: Angiographic in-segment percent diameter stenosis (%DS) in the side branch at 9 months
Other secondary endpoints included a range of safety and effectiveness parameters including acute success, the individual components of TVF (cardiac death, target vessel MI, and TVR), all-cause mortality, rate of stent thrombosis and MACE (and the individual elements of MACE) evaluated at 30 days, 6 and 9 months and annually up to 3 years.
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| Follow-up Visits and Length of Follow-up |
3 years post-index procedure
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
A total of 769 patients were enrolled in the TRYTON Pivotal randomized controlled trial (RCT), which included 704 randomized patients in Europe, Israel, and the United States and 65 US roll-in (non-randomized Tryton Side Branch Stent) patients. In the randomized cohort, 355 subjects were in the Tryton Side Branch Stent group, and 349 subjects were in the balloon angioplasty (POBA) group.
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| Actual Number of Sites Enrolled |
66 sites
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| Patient Follow-up Rate |
All patients were scheduled to return for clinical follow-up assessments at 30 days, 6 months, 9 months, 1 year, 2 years, and 3 years post-index procedure.
Angiographic follow-up at 9 months was obtained in the first 374 randomized patients (N=195 TRYTON cohort, N=181 POBA cohort). Of those enrolled in the angiographic subgroup, an intravascular ultrasound (IVUS) subgroup included 59 TRYTON patients and 35 POBA patients.
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| Final Safety Findings |
The TRYTON Pivotal RCT evaluated the safety and effectiveness of the TRYTON Side Branch Stent with an approved main branch drug-eluting stent (DES) compared to side branch POBA and an approved main branch DES in the treatment of de novo native coronary artery bifurcation lesions (Medina Classification 1.1.1; 0.1.1; 1.0.1). Other anatomic inclusion criteria included a side branch diameter stenosis of greater than or equal to 50%, a lesion length less than or equal to 5.0 mm, and reference vessel diameters (RVDs) greater than or equal to 2.5 mm to less than or equal to 3.5 mm in the side branch and greater than or equal to 2.5 mm to =4.0 mm in the main branch. Key trial results for the ITT population are as follows:
In the ITT population, treatment with the TRYTON Side Branch Stent did not meet the non-inferiority primary clinical endpoint of 9-month target vessel failure (TVF; a composite of cardiac death, target vessel myocardial infarction (MI), and clinically-driven target vessel revascularization) with a TVF rate of 17.2% (60/348) for the TRYTON group compared to a TVF rate of 12.6% (43/341) for the POBA group, principally due to a higher rate of periprocedural MI in the TRYTON Stent group defined by CK-MB elevations (most of which were not associated with clinical sequelae).
Implantation of the TRYTON Stent was associated with low rates of stent thrombosis, clinically significant MIs, cardiac deaths, and clinically-driven target vessel revascularization through 3-years post-procedure.
Clinically-driven TVR was slightly higher in the TRYTON Stent group vs. the POBA group.
At 9-months post-index procedure, the side branch in-segment percent diameter stenosis (%DS) was significantly lower in the TRYTON group compared to the POBA group.
A post hoc analysis of the primary and secondary endpoints in subjects with side branch RVD greater than or equal to 2.25 mm by QCA (>2.5 mm by visual assessment, the “Intended Population”) demonstrated the following:
Treatment with the TRYTON Side Branch Stent was comparable to POBA for TVF at 9-months with a rate of 10.5% (15/143) for the TRYTON group and 14.8% (21/142) for the POBA group.
Clinically-driven TVR rates were comparable in the TRYTON group and the POBA group.
At 9-months post-index procedure, the side branch in-segment %DS was significantly lower in the TRYTON group compared to the POBA group.
Long-term safety endpoint results showed no safety signals in the Tryton Stent group through 3-years post-procedure.
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| Study Strengths & Weaknesses |
Operators enrolled many patients with inappropriately small sized side branches. Only 41% of the ITT population (146 TRYTON subjects and 143 POBA subjects) met the study criterion for a side branch RVD =2.25 mm per quantitative coronary angiography (QCA) assessment, which is generally equivalent to a greater than or equal to 2.5 mm diameter by visual estimation. Enrollment of patients with small side branches was the key factor in the TRYTON Side Branch Stent not meeting the non-inferiority primary clinical endpoint of 9-month TVF compared with POBA.
When the primary endpoint analysis was limited to subjects with side branch RVD greater than to equal to 2.25 mm by QCA (the Intended Population), the 9-month TVF rate was 10.5% (15/143) in the TRYTON group compared to 14.8% (21/142) in the POBA group. Since this was a post-hoc analysis of a selected subgroup, a formal conclusion of non-inferiority of the Tryton Stent vs. POBA cannot be made.
In response to the results of the Tryton Stent Pivotal RCT, the EA Confirmatory Study was initiated to: (1) Confirm the ability of physicians to enroll patients with appropriately-sized side branch diameters to accommodate the TRYTON Stent; (2) Confirm the acute safety profile of the TRYTON Stent (consistent with the post hoc analysis of the pivotal RCT Intended Population) by demonstrating an acceptable periprocedural MI rate; and (3) Confirm the other clinical outcomes observed in the Pivotal RCT Intended Population.
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| Recommendations for Labeling Changes |
The sponsor will be requested to add the complete 3-year follow-up data to the labeling.
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