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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P170030 / PAS002 |
| Date Original Protocol Accepted |
02/22/2019
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| Date Current Protocol Accepted |
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| Study Name |
Bioflow-V Cont f/u PAS
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| Device Name |
ORSIRO Sirolimus Eluting Coronary Stent System
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
Sponsor Registry
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| Comparison Group |
Concurrent Control
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| Analysis Type |
Descriptive
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The BIOTRONIK BIOFLOW-V clinical trial was a prospective, multicenter, randomized, controlled trial combining data on the randomized subjects with data from two prior studies by employing a Bayesian approach.
The objective of this study was to assess the safety and efficacy of the Orsiro Sirolimus Eluting Coronary Stent System in the treatment of subjects with up to three native de novo or restenotic (after standard PTCA only) coronary artery lesions compared with the Xience coronary stent system.
The primary endpoint was TLF rate at 12 months post index procedure.
TLF was defined as all cardiac death, target vessel Q-wave or non–Q-wave MI, or clinically driven TLR. Subjects with CAD who qualified for PCI with stenting were screened per the protocol inclusion and exclusion criteria to achieve a total of up to 1,400 randomized subjects. Eligible subjects were randomized in a 2:1 ratio, stratified by study center, and underwent percutaneous coronary revascularization with either the Orsiro Sirolimus Eluting Stent System (treatment group) or the Xience Everolimus Eluting Stent System (control group).
Subjects may have received treatment of up to three target lesions, one or two target lesions per target vessel, for a maximum of two target vessels. The target lesion(s) were required to be de novo or restenotic lesion(s) of =36 mm in length in native coronary artery(ies), with a reference vessel diameter of 2.25–4.0 mm. Treatment of restenotic lesions was allowed provided that the target lesion was previously treated with PTCA only. All treatment with study stents was to be performed during a single index procedure. Note: Concurrent treatment of non-target lesions during the index procedure was not allowed.
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| Study Population |
Eligible patients were identified based on inclusion/exclusion criteria.
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| Sample Size |
1334 patients and 92 sites
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| Key Study Endpoints |
Primary Endpoints
The primary endpoint was target lesion failure (TLF) rate at 12 months post–index procedure. Target lesion failure was defined as all cardiac death, target vessel Q-wave or non–Q-wave myocardial infarction (MI), or clinically driven target lesion revascularization.
Secondary Endpoints
1. Device success, defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only. Note: Post-dilatation was allowed to achieve device success.
2. Lesion success, defined as attainment of < 30% residual stenosis of target lesion using any percutaneous method.
3. Procedure success, defined as attainment of < 30% residual stenosis of the target lesion using the assigned study stent only without occurrence of in-hospital major adverse cardiac events (MACE).
The following secondary clinical endpoints were evaluated prior to discharge, at 1, 6, and 12 months and annually thereafter through 5 years follow-up:
4. Death.
5. MI.
6. Cardiac death or MI.
7. MACE and individual MACE components (MACE: composite of all-cause death, Q-wave or non–Q-wave MI, and any clinically-driven target lesion revascularization [TLR]).
8. TLF and individual TLF components (TLF: composite of cardiac death, target vessel Q-wave or non–Q-wave MI, and any clinically-driven TLR).
9. Target vessel failure (TVF) and individual TVF components (TVF: composite of cardiac death, target vessel Q-wave or non–Q-wave MI, and any clinically-driven target vessel revascularization [TVR]).
10. Stent thrombosis (all, definite, definite/probable, probable, possible) according to Academic Research Consortium (ARC) criteria for acute, subacute, late, very late and cumulative stent thrombosis.
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
1,334 subjects
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| Actual Number of Sites Enrolled |
92 sites, both US and OUS (13 countries)
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| Patient Follow-up Rate |
Minimum of 95% follow-up rate
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| Final Safety Findings |
The Orsiro group maintained significantly lower rates of target vessel MI: 4.69% compared to 8.25% (P=0.016) in the Xience group (primary driver of lower TLF in Orsiro patients vs Xience patients). A total of 29.41% (260/884) Orsiro subjects and 31.78% (143/450) Xience subjects experienced at least one device/procedure related AE. A total of 8.94% (79/884) Orsiro subjects and 12.44% (56/450) Xience subjects experienced at least one device/procedure related SAE None of the device/procedure related AEs or SAEs was significantly more prevalent in the Orsiro group compared to the Xience group as evidenced by posterior probability rates < 97.5%. There have been no U(S)ADEs reported in the BIOFLOW-V clinical trial through 5 years post-procedure.
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| Final Effect Findings |
In analysis of non-inferiority of Orsiro versus Xience with regards to the primary endpoint of 12-month TLF were 6.32% and 8.90%, respectively. Through 3 years post-procedure, the rates of clinically driven TLR and clinically driven TVR emerged to be significantly lower in the Orsiro group compared to the Xience group: 3.32% vs. 6.14% (P=0.024) for clinically-driven TLR and 5.53% vs 9.80% (P=0.008) for clinically-driven TVR. The numerical differences in clinically-drive TLR and clinically driven TVR were no longer statistically significant at 4 and 5 years. Driven by the significantly lower target vessel MI rate and lower clinically driven TVR rate, the rate of the composite of TVF was also significantly lower in the Orsiro group at 2, 3 and 4 years with a statistical trend at 5 years post procedure.
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| Study Strengths & Weaknesses |
This was a randomized, controlled trial that met its primary endpoint. However, the trial demographics were not diverse with respect to race and sex, with a large percent of the subjects being White or male.
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| Recommendations for Labeling Changes |
Labeling change is recommended to reflect the long-term data from the post-approval study. The labeling change should include a new section on the label showing a summary of the post-approval study methods (including study objectives, design, population, number of enrolled site/subjects, key endpoints, follow-up visits, etc.), results and study strengths and limitations of the PAS.
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