• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

  • Print
  • Share
  • E-mail
-

The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

Learn more...


             

Longterm IDE Follow up


Suggest Enhancement / Report Issue | export reports to excelExport to Excel
General
Application Number P070015 / PAS001
Current Plan Approved 07/02/2008
Study Name Longterm IDE Follow up
General Study Protocol Parameters
Study Design Randomized Clinical Trial
Data Source Sponsor Registry
Comparison Group Concurrent Control
Analysis Type Analytical
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description Approximately 1125 subjects were originally planned to be enrolled in the study; however, the study was expanded to 3690 subjects. Subjects in the SPIRIT IV clinical study were randomized 2:1, with 2460 subjects to receive XIENCE V and 1230 subjects to receive TAXUS.
Study Population Description This device is indicated for improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length < 28 mm) with reference vessel diameters of 2.5 mm to 4.25 mm. The study population consisted of the long term follow-up of pateints enrolled in the SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 and SPIRIT IV trials.
Sample Size SPIRIT FIRST: 60 patients, 9 sites, SPIRIT II: 300 patients, no site maximum specified, SPIRIT III RCT: 1002 patients, 65 sites, SPIRIT III 4.0: 80 patients, 30 sites. SPIRIT IV: 3690 patients, 66 sites
Data Collection The primary endpoint of the SPIRIT FIRST clinical study was in-stent LL at 180 days on the per-treatment evaluable population. The primary endpoint of the SPIRIT II trial was in-stent LL at 180 days. The primary endpoint of the SPIRIT III RCT was in-segment LL at 240 days and the major secondary endpoint was ischemia-driven target vessel failuer at 270 days. The primary endpoint of the SPIRIT III 4.0 mm trial was in-segment LL at 240 days. The primary endpoint of the SPIRIT IV trial was target lesion failure at 1 year.
Follow-up Visits and Length of Follow-up SPIRIT FIRST: Patients were evaluated at 30, 180, 270 days and 1, 2, and 3 years following the index procedure. Angiography and IVUS in all patients were performed at 180 days and 1 year post index procedure.; SPIRIT II: Patients were evaluated at 30, 180, 270 days and 1, 2 and 3 years following the index procedure. Angiography in all patients and IVUS on a pre-specified subset of patients (N=152) was performed at 180 days post index procedure. Additionally, 2-year angiography and IVUS was performed in a subset of patients (N=152).; SPIRIT III RCT: Subjects were evaluated at 30, 180, 240, 270 days, one year, and two years following the index procedure. Further clinical observations will be performed at 3 years for all subjects. Angiography was to be performed on all subjects in group A and group B at 240-day follow-up.; SPIRIT III: Subjects were evaluated at 30, 180, 240, 270 days, and one and two years following the index procedure. Further clinical observations will be performed per protocol in newly enrolled subjects and at 3 years for all subjects. Angiography was to be performed on all subjects at their 240-day follow-up. Target enrollment remains 80 subjects
Final Study Results
Interim Safety Information SPIRIT 1st - 87% of patients (49/56) had a 5 yr clinical follow-up (24 for VISION-E and 25 in the VISION control). The target vessel failure (TVF) rates were 17% in the VISION-E test vs. 36% in the VISION control arm. The major adverse cardiac event (MACE) rates were 17% for VISION-E vs. 28% VISION control. Patients enrolled in the VISION-E test arm did not experience any additional MACE or TVF events between 1- and 5-yr follow-up. Due to 2 patients lost to follow-up at 5 yrs, the hierarchical MACE/TVF rates for VISION-E increased from 15% at 1-yr to 17% at 5 yr. All major endpoints for VISION-E were better than VISION control. While the number of patients was small, the results do not raise concerns.

SPIRIT II - Results at 4 yrs do not raise any concerns. The rates of ischemia-driven (ID)-TVF, ID-MACE, MI, ID- target lesion revascularization (TLR) and cardiac death are lower in the XIENCE V arm vs. TAXUS arm. Kaplan-Meier (KM) estimates indicated clinical differences in ID-MACE rates in favor of the XIENCE V, 7%, vs. TAXUS, 15% (p=0.042) as well as in cardiac death rates in favor of the XIENCE V, 0.5%,vs. TAXUS, 4% (p=0.024). Non-hierarchical NQMI and non-hierarchical ID-TLR rates were lower in XIENCE V, 4% and 5%, vs. TAXUS, 8% and 10%. Low rates of stent thrombosis were found for XIENCE V and TAXUS for per protocol and ARC definitions.

SPIRIT III RCT - Results at 3 yrs do not raise concerns for the safety and effectiveness of the XIENCE V. It exhibits lower rates of TVF, MACE, TLR, and TVR, non-TLR vs. TAXUS. There was a 29% reduction in the 3-yr TVF rates in the XIENCE V vs. TAXUS (14% vs. 20%). There was a 41% reduction in MACE rates for XIENCE V vs. TAXUS arm (10% and 16%). KM estimate indicated clinical difference in TVF and MACE-free survival rates for XIENCE V. XIENCE V had lower TLR (6%) vs. TAXUS, 9%.. The TVR, non-TLR rates were also lower in the XIENCE V arm (7%) vs. TAXUS arm (9%). There were low rates of stent thrombosis for XIENCE V and TAXUS per protocol and ARC definitions.

SPIRIT III 4.0mm - Of the 73 enrolled, follow-up rate at 2 yrs was 90% (62/69). The TVF rates were 8% (5/65) for XIENCE V 4.0 mm arm, 16% (50/305) for TAXUS RCT, and 11% (72/637) for XIENCE V RCT. The MACE rates were 8% (5/65) for XIENCE V 4.0 mm, 14% (42/305) for TAXUS RCT, and 8% (49/637) for XIENCE V RCT. The difference in MACE rates between XIENCE V 4.0 mm and TAXUS RCT represented a reduction of 44% for XIENCE V 4.0 mm. TLR rates were 2% (1/65) for XIENCE V 4.0 mm, 8% (23/305) for TAXUS RCT and 5% (29/637) for XIENCE V RCT. The difference in TLR rates between XIENCE V 4.0 mm and TAXUS RCT represented a reduction of 80% in the XIENCE V 4.0 mm arm. XIENCE V 4.0 mm had not TVR procedures (0/65). TVR rates were7% (20/305) for TAXUS RCT and 5% (31/637) for XIENCE V RCT. KM estimates showed that revascularization-free survival rates through 758 days were clinically different for XIENCE V 4.0 mm, (99%) vs. TAXUS RCT (89%). The stent thrombosis rates per protocol for XIENCE V 4.0 mm vs. TAXUS RCT arm were, acute (1% and 0%); subacute (0% and 0%); late (0% and 0.6%), and very late (1.6% and 1.0%), as defined in the protocol. The stent thrombosis rates for XIENCE V 4.0 mm and XIENCE V RCT were comparable.

SPIRIT IV - At 1-yr, there was a 29% TVF reduction, 14% DMR reduction, 39% reduction in MACE, and 26% ID-TVR (non-TLR) reduction XIENCE V patients. For stent thrombosis rates, the overall per protocol results were 0.17% for XIENCE V vs. TAXUS (0.85%). The overall ARC-defined (definite/probable) stent thrombosis rate was lower for XIENCE V vs. TAXUS, (0.29% and 1.10%). The results of the SPIRIT IV clinical trial at 1-yr do not raise any concerns in terms of the safety and effectiveness of XIENCE V and demonstrate positive results compared with the TAXUS control.

Number of Patients SPIRIT FIRST: 60

SPIRIT II: 300

SPIRIT III (RCT): 1002

SPIRIT III (4.0mm size): 73

SPIRIT IV: 3687

Number of Sites SPIRIT FIRST: 9

SPIRIT II: 28

SPIRIT III (RCT): 65

SPIRIT III (4.0mm size): 30

SPIRIT IV: 66

Follow-up Rate SPIRIT FIRST: 87% SPIRIT II: 81%

SPIRIT III (RCT): 84.3% SPIRIT III (4.0mm size): 88% SPIRIT IV: 90.9%

Safety Findings SPIRIT FIRST

No stent thrombosis events reported in either arm in the SPIRIT FIRST study through the five- year follow-up time point per protocol definition and per ARC definition.



SPIRIT II

The stent thrombosis rate was numerically lower for XIENCE V compared to TAXUS at 5 years (0.9% vs. 2.8%) per ARC definition. No stent thrombosis events were observed since the 3 year endpoint in the XIENCE V arm.



SPIRIT III (RCT)

The stent thrombosis rates overall were numerically low and comparable between the XIENCE V and TAXUS RCT arms respectively, (1.55 versus 1.87%) per ARC definition.



SPIRIT III (4.0mm size)

Overall Stent Thrombosis rates per ARC definitions at 5 years were 0%, suggesting relative safety of the device as compared to the TAXUS RCT arm.



SPIRIT IV

Overall Stent Thrombosis (ST) rates per ARC definitions at 3 years were 0.62% (14/2263) for

XIENCE V arm, and 1.73% (19/1098) for TAXUS arm. ST rates in the XIENCE V arm was <

1% suggesting relative safety of the device as compared to the TAXUS RCT arm.

Effect Findings SPIRIT FIRST

The five-year follow-up rates of TVF remained favorable in the XIENCE V arm, 16.7% (4/24) compared to the VISION arm, 36.0% (9/25). The MACE rates were 16.7% (4/24) in the XIENCE V arm and 28.0% (7/25) in the VISION arm.



SPIRIT II

Five-year cardiac mortality was significantly lower in the XIENCE V arm than in the TAXUS arm (1.5% vs. 7.3%, p=0.015). Cardiac Death and MI was lower, yet not statistically significant (4.8% vs. 11.4%) and lower ID-TLR (4.7% vs. 9.4%) in the XIENCE V arm than in the TAXUS arm. As a result, there was a consistent reduction in ID-MACE for XIENCE V vs. TAXUS (ID- MACE 8.0% vs. 18.1%, p=0.018)



SPIRIT III (RCT)

At five years, the XIENCE V arm TVF rate was 20.3% (123/605) compared to 26.6% (76/286)

in the TAXUS arm. Cardiac death rates in the XIENCE V arm was 2.8% (17/605) and was 4.5% (13/286) in the TAXUS arm through five years with numerically low rates of MI sustained in the XIENCE V arm (4.6% 28/605) compared to the TAXUS arm (7.0% 20/286). TLR rates were

also more favorable in the XIENCE V arm through five years in the XIENCE V arm (8.9%

54/605) compared to the TAXUS arm (12.9% 37/286).



SPIRIT III (4.0mm size)

Rates of key clinical events and angiographic endpoints were lower in the XIENCE V arm than in the TAXUS RCT arm out to 5 years as follows:

- MACE Rates at 5 years: 10.4% (as compared to 22% in TAXUS RCT arm)

- TLR rates at 5 years: 4.5% (as compared to 12.9% in TAXUS RCT arm)

- TVF rates at 5 years: 11.9% ( as compared to 26.6% in TAXUS RCT arm)



SPIRIT IV

The rates of key clinical events and angiographic endpoints were lower in the XIENCE V arm than in the TAXUS arm out to 3 years as follows:



- MACE Rates at 3 years: XIENCE V: 9.8% (231/2348) as compared to TAXUS: 12.3% (142/1158)

- TLR rates at 3 years: XIENCE V: 6.3% (148/2348) as compared to TAXUS: 7.9% (92/1158)

- TVF rates at 3 years: XIENCE V: 13.3% (312/2348) as compared to TAXUS: 14.5% (168/1158)

- TLF rates at 3 years: XIENCE V: 9.5% (233/2348) as compared to TAXUS: 11.9% (138/1158)

Strengths & Weaknesses Results from each of the five clinical studies for XIENCE V® including: SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 mm, and SPIRIT IV provide further evidence of the clinical utility and safety of this device.
Label Changes Post-approval study findings from each of the five clinical studies for XIENCE V® including: SPIRIT FIRST, SPIRIT II, SPIRIT III RCT, SPIRIT III 4.0 mm, and SPIRIT IV should be part of the device labeling.


Longterm IDE Follow up Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
1 year report 02/26/2009 02/12/2010 On Time
2 year report 07/02/2010 06/29/2010  
3 year report 07/02/2011 04/22/2011 On Time
unsolicited report 06/13/2012 06/13/2012 On Time
3 year follow-up report 06/25/2012 06/25/2012 On Time
4 year report 07/01/2012 01/17/2012 On Time
final report for SPIRIT III and SPIRIT IV 07/01/2013 05/01/2013 On Time
three year follow up report 08/20/2013 08/20/2013 On Time


Contact Us

Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v Silver Spring, MD
20993-0002

Phone: (301) 796-6134
Fax: (301) 847-8140
julie.unger@fda.hhs.gov

Related Links

-
-