Pre-Market Clinical Trials - Abbott XIENCE Sierra Manual

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
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
Study • Multi-center • Multi-center
Type / Design • Randomized • Randomized
• Single-blinded • Single-blinded
• Active-control • Active-control
Number of Subjects Total: 1,002 Total: 3,690
Enrolled
XIENCE V: 668 XIENCE V: 2,460
TAXUS Express TAXUS Express Control: 1,230
Control: 334
Up to two de novo Up to three de novo lesions,
Treatment
lesions in different maximum of two lesions per
epicardial vessels epicardial vessel
Lesion Size RVD: ≥ 2.5 ≤ 3.75 mm RVD: ≥ 2.5 ≤ 4.25 mm
Length: ≤ 28 mm Length: ≤ 28 mm
In-segment late loss at Ischemia-driven target lesion
Primary Endpoint
240 days failure at 1 year (composite of
cardiac death, target vessel MI or
ischemia-driven TLR)
TVF at 270 days None
Co-Primary Endpoint
Clinical Follow-up 30, 180, 240, 270 30, 180, 270 days,
days,
1 to 3 years
1 to 5 years
Angiographic 240 days (N = 564) None
Follow-up
1 In the TAXUS stent arm, there was 1 subject who received 1 TAXUS
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.
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Express stent (TAXUS stent). The SPIRIT IV trial is a prospective, randomized, active-controlled, single-blinded, multi-
® ®
SPIRIT Small Vessel
SPIRIT IV
Registry
• Multi-center • Multi-center
• Open-label • Open-label
• Single-arm • Single-arm
Total: 150 Total: 400
2.25 mm XIENCE V XIENCE PRIME
1
Up to two de novo lesions in Up to two de novo lesions
different epicardial vessels in different epicardial
vessels
RVD: ≥ 2.25 < 2.50 mm RVD: ≥ 2.25 ≤ 4.25 mm
2
Length: ≤ 28 mm Length: ≤ 22 mm
TLF (target lesion failure) TLF (target lesion failure)
at 1 year at 1 year
None None
30 days, 240 days, 30, 180 days,
1 to 3 years 1 to 3 years
240 days (N = 69) None
® Liberté ® stent.
Table 10.1-3: SPIRIT Family of Clinical Trials
Principal 1-Year Clinical Outcomes (Pre-market)
SPIRIT IV
XIENCE V TAXUS
(N = 2458) (N = 1229)
4.0% 6.8%
TLF
(97/2416) (81/1195)
5.5% 7.7%
TVF
(134/2416) (92/1195)
4.1% 6.9%
MACE
(98/2416) (82/1195)
1.0% 1.3%
All Death
(25/2416) (15/1195)
0.4% 0.4%
Cardiac Death
(10/2416) (5/1195)
1.9% 3.1%
MI
(45/2416) (37/1195)
2.2% 3.3%
Cardiac Death or MI
(54/2416) (39/1195)
2.3% 4.6%
Ischemia-Driven TLR
(56/2416) (55/1195)
2.2% 2.4%
Ischemia-Driven TVR,
Non TL
(54/2416) (29/1195)
Stent Thrombosis
0.29% 1.10%
ARC (Definite / Probable)
(7/2391) (13/1181)
0.3% 0.8%
ARC (Definite)
(6/2385) (10/1183)
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.
SPIRIT PRIME Clinical Trial
Core Size Registry Long Lesion Registry
• Multi-center
• Open-label
• Single-arm
Total: 100
XIENCE PRIME
Up to two de novo lesions in
different epicardial vessels
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
TLF (target lesion failure) at 1 year
None
30, 180 days,
1 to 3 years
None
SPIRIT Small
SPIRIT III RCT
Vessel
2.25 mm
XIENCE V TAXUS
XIENCE V
(N = 669) (N = 333)
(N = 144)
5.3% 9.7% 8.1%
(35/655) (31/319) (11/136)
8.5% 11.6% 11.0%
(56/655) (37/319) (15/136)
6.0% 10.3% 8.1%
(39/655) (33/319) (11/136)
1.2% 1.3% 1.5%
(8/657) (4/320) (2/136)
0.8% 0.9% 1.5%
(5/657) (3/320) (2/136)
2.7% 4.1% 1.5%
(18/655) (13/319) (2/136)
3.4% 4.7% 2.9%
(22/655) (15/319) (4/136)
3.4% 5.6% 5.1%
(22/655) (18/319) (7/136)
3.2% 4.7% 5.9%
(21/655) (15/319) (8/136)
0.9% 0.6% 1.5%
(6/650) (2/316) (2/136)
0.8% 0.3% 0.7%
(5/650) (1/317) (1/138)
Printed on : 2017-11-03
Table 10.1-2: SPIRIT Family of Clinical Trials
Angiographic Results (Pre-market)
SPIRIT III RCT
240 Days
Angiographic
XIENCE V TAXUS
Results
(N = 376) (N = 188)
(M = 427) (M = 220)
In-Stent Late Loss
0.16 ± 0.41 (342) 0.30 ± 0.53 (158)
(mm)
In-Segment Late
0.14 ± 0.39 (343) 0.26 ± 0.46 (158)
Loss (mm)
In-Stent Binary
2.3% (8/343) 5.7% (9/158)
Restenosis
In-Segment Binary
4.7% (16/344) 8.9% (14/158)
Restenosis
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).
SPIRIT PRIME
Clinical Trial
Core Size Long Lesion
Registry Registry
(N = 401) (N = 104)
4.5% 7.7%
(18/399) (8/104)
N/A N/A
4.5% 7.7%
(18/399) (8/104)
0.8% 1.0%
(3/399) (1/104)
0.3% 0.0%
(1/399) (0/104)
1.8% 4.8%
(7/399) (5/104)
2.0% 4.8%
(8/399) (5/104)
2.5% 2.9%
(10/399) (3/104)
2.8% 2.9%
(11/399) (3/104)
0.5% 0.0%
(2/399) (0/104)
0.5% 0.0%
(2/399) (0/104)
SPIRIT Small Vessel
240 Days
2.25 mm XIENCE V
(N = 69)
(M = 69)
0.20 ± 0.40 (52)
0.16 ± 0.41 (52)
3.8% (2/52)
9.6% (5/52)