10.1 Pre-market Clinical Trials
Principal safety and effectiveness of the XIENCE V stent has been established from a series of pre-market clinical trials. SPIRIT III RCT was the pivotal randomized clinical trial (RCT) that
established the non-inferiority of the XIENCE V stent to the TAXUS
®
Express
®
stent (TAXUS stent). The SPIRIT IV trial is a prospective, randomized, active-controlled, single-blinded, multi-
center evaluation of the XIENCE V stent compared to the TAXUS Express stent (TAXUS stent) in the treatment of up to three
de novo
lesions ≤ 28 mm in length in native coronary arteries
with RVD ≥ 2.5 mm to ≤ 4.25 mm. The SPIRIT IV trial established the superiority of the XIENCE V stent compared to the TAXUS Express stent. The SPIRIT Small Vessel (SV) Registry is a
prospective, single-arm, open-label, US multi-center registry study that established the safety and effectiveness of the XIENCE V 2.25 mm diameter stent. SPIRIT PRIME is a prospective,
open-label, multi-center nonrandomized clinical trial with two study arms using the core size XIENCE PRIME and XIENCE PRIME LL stent system that established the safety and effectiveness
of the XIENCE PRIME and XIENCE PRIME LL stents. Tables 10.1-1 through 10.1-4 present the trial designs, angiographic results (for studies that required angiographic follow-up), and
principal clinical outcomes at 1-year and from latest follow-up, respectively.
Table 10.1-1: SPIRIT Family of XIENCE V Clinical Trial Designs (Pre-market)
SPIRIT III RCT
SPIRIT IV
SPIRIT Small Vessel
Registry
SPIRIT PRIME Clinical Trial
Core Size Registry
Long Lesion Registry
Study
Type / Design
•
Multi-center
•
Randomized
•
Single-blinded
•
Active-control
•
Multi-center
•
Randomized
•
Single-blinded
•
Active-control
•
Multi-center
•
Open-label
•
Single-arm
•
Multi-center
•
Open-label
•
Single-arm
•
Multi-center
•
Open-label
•
Single-arm
Number of Subjects
Enrolled
Total: 1,002
XIENCE V: 668
TAXUS Express
Control: 334
Total: 3,690
XIENCE V: 2,460
TAXUS Express Control: 1,230
1
Total: 150
2.25 mm XIENCE V
Total: 400
XIENCE PRIME
Total: 100
XIENCE PRIME
Treatment
Up to two
de novo
lesions in different
epicardial vessels
Up to three
de novo
lesions,
maximum of two lesions per
epicardial vessel
Up to two
de novo
lesions in
different epicardial vessels
Up to two
de novo
lesions
in different epicardial
vessels
Up to two
de novo
lesions in
different epicardial vessels
Lesion Size
RVD: ≥ 2.5 ≤ 3.75 mm
Length: ≤ 28 mm
RVD: ≥ 2.5 ≤ 4.25 mm
2
Length: ≤ 28 mm
RVD: ≥ 2.25 < 2.50 mm
Length: ≤ 28 mm
RVD: ≥ 2.25 ≤ 4.25 mm
Length: ≤ 22 mm
XIENCE PRIME CS:
RVD: ≥ 2.25 ≤ 4.25 mm
Length: ≤ 22 mm
XIENCE PRIME LL:
RVD: ≥ 2.5 ≤ 4.25 mm
Length: > 22 mm and ≤ 32 mm
Primary Endpoint
In-segment late loss at
240 days
Ischemia-driven target lesion
failure at 1 year (composite of
cardiac death, target vessel MI or
ischemia-driven TLR)
TLF (target lesion failure)
at 1 year
TLF (target lesion failure)
at 1 year
TLF (target lesion failure) at 1 year
Co-Primary Endpoint
TVF at 270 days
None
None
None
None
Clinical Follow-up
30, 180, 240, 270
days,
1 to 5 years
30, 180, 270 days,
1 to 3 years
30 days, 240 days,
1 to 3 years
30, 180 days,
1 to 3 years
30, 180 days,
1 to 3 years
Angiographic
Follow-up
240 days (N = 564)
None
240 days (N = 69)
None
None
1
In the TAXUS stent arm, there was 1 subject who received 1 TAXUS
®
Liberté
®
stent.
2
RVD ≥ 2.5 mm to ≤ 3.75 mm and stent sizes up to 3.5 mm until 4.0 mm TAXUS is commercially available.
Table 10.1-2: SPIRIT Family of Clinical Trials
Angiographic Results (Pre-market)
Angiographic
Results
SPIRIT III RCT
240 Days
SPIRIT Small Vessel
240 Days
XIENCE V
(N = 376)
(M = 427)
TAXUS
(N = 188)
(M = 220)
2.25 mm XIENCE V
(N = 69)
(M = 69)
In-Stent Late Loss
(mm)
0.16 ± 0.41 (342) 0.30 ± 0.53 (158)
0.20 ± 0.40 (52)
In-Segment Late
Loss (mm)
0.14 ± 0.39 (343) 0.26 ± 0.46 (158)
0.16 ± 0.41 (52)
In-Stent Binary
Restenosis
2.3% (8/343)
5.7% (9/158)
3.8% (2/52)
In-Segment Binary
Restenosis
4.7% (16/344)
8.9% (14/158)
9.6% (5/52)
Notes:
– Data are mean (mm) ± SD or % (n/N).
– N is total number of patients. M is total number of lesions.
– SPIRIT III and SV 240-day include follow-up window (240 + 28 days).
Table 10.1-3: SPIRIT Family of Clinical Trials
Principal 1-Year Clinical Outcomes (Pre-market)
SPIRIT IV
SPIRIT III RCT
SPIRIT Small
Vessel
SPIRIT PRIME
Clinical Trial
XIENCE V
(N = 2458)
TAXUS
(N = 1229)
XIENCE V
(N = 669)
TAXUS
(N = 333)
2.25 mm
XIENCE V
(N = 144)
Core Size
Registry
(N = 401)
Long Lesion
Registry
(N = 104)
TLF
4.0%
(97/2416)
6.8%
(81/1195)
5.3%
(35/655)
9.7%
(31/319)
8.1%
(11/136)
4.5%
(18/399)
7.7%
(8/104)
TVF
5.5%
(134/2416)
7.7%
(92/1195)
8.5%
(56/655)
11.6%
(37/319)
11.0%
(15/136)
N/A
N/A
MACE
4.1%
(98/2416)
6.9%
(82/1195)
6.0%
(39/655)
10.3%
(33/319)
8.1%
(11/136)
4.5%
(18/399)
7.7%
(8/104)
All Death
1.0%
(25/2416)
1.3%
(15/1195)
1.2%
(8/657)
1.3%
(4/320)
1.5%
(2/136)
0.8%
(3/399)
1.0%
(1/104)
Cardiac Death
0.4%
(10/2416)
0.4%
(5/1195)
0.8%
(5/657)
0.9%
(3/320)
1.5%
(2/136)
0.3%
(1/399)
0.0%
(0/104)
MI
1.9%
(45/2416)
3.1%
(37/1195)
2.7%
(18/655)
4.1%
(13/319)
1.5%
(2/136)
1.8%
(7/399)
4.8%
(5/104)
Cardiac Death or MI
2.2%
(54/2416)
3.3%
(39/1195)
3.4%
(22/655)
4.7%
(15/319)
2.9%
(4/136)
2.0%
(8/399)
4.8%
(5/104)
Ischemia-Driven TLR
2.3%
(56/2416)
4.6%
(55/1195)
3.4%
(22/655)
5.6%
(18/319)
5.1%
(7/136)
2.5%
(10/399)
2.9%
(3/104)
Ischemia-Driven TVR,
Non TL
2.2%
(54/2416)
2.4%
(29/1195)
3.2%
(21/655)
4.7%
(15/319)
5.9%
(8/136)
2.8%
(11/399)
2.9%
(3/104)
Stent Thrombosis
ARC (Definite / Probable)
0.29%
(7/2391)
1.10%
(13/1181)
0.9%
(6/650)
0.6%
(2/316)
1.5%
(2/136)
0.5%
(2/399)
0.0%
(0/104)
ARC (Definite)
0.3%
(6/2385)
0.8%
(10/1183)
0.8%
(5/650)
0.3%
(1/317)
0.7%
(1/138)
0.5%
(2/399)
0.0%
(0/104)
Notes:
– All counts presented in this table are subject counts. Subjects are counted only once for each event for each time period.
– 1-year includes the follow-up window (365 + 28 days) for all trials.
– TLF includes cardiac death, MI attributed to target vessel and ischemia-driven TLR. SPIRIT SV and PRIME used clinically indicated TLR definition rather
than ischemia-driven TLR.
– TVF includes cardiac death, MI, ischemia-driven TLR and TVR, non-target lesion. SPIRIT SV and PRIME used clinically indicated TLR and TVR definition
rather than ischemia-driven TLR and TVR definition, which was used for SPIRIT II, SPIRIT III, and SPIRIT IV.
– MACE includes cardiac death, MI and ischemia-driven TLR.
EL2115538 (2017-1
1-03
)
Page 7 of 206
Printed on : 2017-11-03
