Clinical trial NCT00180479: SPIRIT III Clinical Trial of the XIENCE V® Everolimus Eluting Coronary Stent System (EECSS)
Official title: SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V® Everolimus Eluting Coronary Stent System (EECSS) in the Treatment of Subjects With de Novo Native Coronary Artery Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stents
Coronary Artery Disease
Total Coronary Occlusion
Coronary Artery Restenosis
Stent Thrombosis
Vascular Disease
Myocardial Ischemia
Coronary Artery Stenosis
Keywords: Everolimus
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2005-09-16
Enrollment: 1002
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is divided into 5 arms:

1. Randomized Clinical Trial (RCT): Prospective, randomized, active-controlled, single blind, parallel two-arm multi-center clinical trial in the United States (US) comparing XIENCE V® Everolimus Eluting Coronary Stent System (CSS) (2.5, 3.0, 3.5 mm diameter stents) to the Food and Drug Administration (FDA) approved commercially available active control TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System
2. US 2.25 mm non-randomized arm using 2.25 mm diameter XIENCE V® Everolimus Eluting CSS
3. US 4.0 mm non-randomized arm using 4.0 mm diameter XIENCE V® Everolimus Eluting CSS
4. US 38 mm non-randomized arm using 38 mm in length XIENCE V® Everolimus Eluting CSS
5. Japanese non-randomized arm using XIENCE V® Everolimus Eluting CSS (2.5, 3.0, 3.5, 4.0 mm diameter stents) in Japan

The TAXUS® EXPRESS2™ Paclitaxel Eluting Coronary Stent System is Manufactured by Boston Scientific.

Detailed description: The purpose of the SPIRIT III clinical trial is to evaluate the safety and efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS). The XIENCE V® EECS (XIENCE V® arm) will be compared to an active control group represented by the FDA approved commercially available Boston Scientific TAXUS® EXPRESS2™ Paclitaxel-Eluting Coronary Stent (TAXUS® EXPRESS2™ PECS) System (TAXUS® arm).

The SPIRIT III clinical trial consists of a randomized clinical trial (RCT) in the US which will enroll approximately 1,002 subjects (2:1 randomization XIENCE V® EECS : TAXUS® EXPRESS2™ PECS) with a maximum of two de novo native coronary artery lesion treatment within vessel sizes \>= 2.5 mm and \<= 3.75 mm.

The SPIRIT III clinical trial also consists of three concurrent US non-randomized arms (2.25 mm diameter stent, 4.0 mm diameter stent and 38 mm length stent arms) and one Japanese non-randomized arm as follows:

1. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 2.25 mm and \< 2.5 mm and lesion length \<= 22 mm will be enrolled concurrently in the US 2.25 mm non-randomized treatment arm
2. 80 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 3.75 mm and \>= 4.25 mm and lesion length \<= 28 mm will be enrolled concurrently in the US 4.0 mm non-randomized treatment arm
3. 105 subjects with a maximum of two de novo native coronary artery lesion within vessel sizes \> 3.0 mm and \< 4.25 mm and lesion length \> 24 mm and \< 32 mm will be enrolled concurrently in the US 38 mm non-randomized treatment arm.
4. 88 Japanese subjects with a maximum of two de novo native coronary artery lesions within vessel sizes \>= 2.5 mm and \<= 4.25 mm and lesion length \<= 28 mm will be enrolled concurrently in the non-randomized Japanese arm.

All subjects in the RCT and the four non-randomized arms will be screened per the protocol required inclusion/exclusion criteria. The data collected will be compared to data from the subjects enrolled into the TAXUS® arm of US RCT.

Subjects enrolled in the US RCT will be sub-grouped based on whether they will have an angiographic and/or an intravascular ultrasound (IVUS) follow-up at 240 days as follows:

Group A: Angiographic and IVUS follow-up at 240 days (N=240) Group B: Angiographic follow-up at 240 days (N=324) Group C: No angiographic or IVUS follow-up (N=438)

All subjects will have clinical follow-up at 30, 180, 240 and 270 days (Data collected through 270 days will be submitted as the primary data set for US and Japanese market approval), and 1, 2, 3, 4, and 5 years (for annual reports).

All subjects enrolled into three US non-randomized arms (N=105 for 2.25 mm arm, N=80 for 4.0 mm arm and N=105 for 38 mm stent arm) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic follow-up at 240 days. No IVUS follow-up is required for subjects enrolled in these arms.

All subjects enrolled into the Japanese non-randomized arm (N=88) will have clinical follow-up at 30, 180, 240, and 270 days, and angiographic and IVUS follow-up at 240 days.

All subjects who receive a bailout stent will be assigned to Group A follow-up subgroup (angiographic and IVUS follow-up at 240 days after the index procedure), regardless of their primary assignment at randomization. At sites without IVUS capability, subjects receiving bailout stent will be assigned to Group B follow-up subgroup (angiographic follow-up at 240 days after the index procedure). Angiographic follow-up is required for all bailout subjects at 240 days.

Data from the US RCT will be submitted to the FDA as the primary data set for product approval for RVD \>= 2.5 mm and \<= 3.75 mm (2.5 mm, 3.0 mm and 3.5 mm stents). Combined data of the US trial/Japanese non-randomized arm will be submitted to the Japanese Ministry of Health, Labor and Welfare (MHLW) for Japanese approval for RVD\>=2.5 mm and \<= 4.25 mm (2.5 mm, 3.0 mm 3.5 mm and 4.0 mm stents). Data from the Japanese non-randomized arm will be submitted to the FDA as additional safety data. Data from the US non-randomized arms of the trial will be the primary data sets for approval for 2.25 mm diameter stent (RVD \> 2.25 mm and \< 2.5 mm), 4.0 mm diameter stent (RVD \> 3.75 mm and \<= 4.25 mm) and 38 mm length stent (RVD \> 3.0 mm and \<= 4.25 mm and lesion length \> 24 mm and \<= 32 mm), respectively in the US.

A pharmacokinetic substudy will be carried out in a minimum of 5 pre-determined sites in the US and a minimum of 5 pre-determined sites in Japan. In the US, the pharmacokinetics (PK) of everolimus, as delivered by the XIENCE V® EECS will be analyzed in a subset of 15 subjects (minimum) with single vessel/lesion treatment, and up to 20 subjects with dual vessel/lesion treatment, respectively. In Japan, a minimum of 10 subjects with single vessel/lesion treatment and up to 20 subjects with dual vessel/lesion treatment will have a PK measurements performed. These subsets will include subjects receiving overlapping stents.

Eligibility criteria: Inclusion Criteria:

* Target lesion(s) must be located in a native epicardial vessel with visually estimated diameter between \>= 2.25 mm and \<= 4.25 mm and a lesion length \<= 32 mm
* The target lesion(s) must be in a major artery or branch with a visually estimated stenosis of \>= 50% and \< 100% with a thrombolysis in myocardial infarction (TIMI) flow of \>= 1
* Non-study, percutaneous intervention for lesions in a non-target vessel is allowed if done \>= 90 days prior to the index procedure (subjects who received brachytherapy will be excluded from the trial)

Exclusion Criteria:

* Located within an arterial or saphenous vein graft or distal to a diseased (vessel irregularity per angiogram and \> 20% stenosed lesion by visual estimation) arterial or saphenous vein graft
* Lesion involving a bifurcation \>= 2 mm in diameter or ostial lesion \> 50% stenosed by visual estimation or side branch requiring predilatation
* Located in a major epicardial vessel that has been previously treated with brachytherapy
* Located in a major epicardial vessel that has been previously treated with percutaneous intervention \< 9 months prior to index procedure
* Total occlusion (TIMI flow 0), prior to wire passing
* The target vessel contains thrombus
* Another significant lesion (\> 40% diameter stenosis \[DS\]) is located in the same epicardial vessel as the target lesion

Primary outcomes:
measure: Primary Endpoint: In-segment Late Loss (LL)
timeFrame: 240 days
Secondary outcomes:
measure: Major Secondary Endpoint: Ischemia Driven Target Vessel Failure (ID-TVF)
timeFrame: 270 days
measure: Target Vessel Failure (TVF)
timeFrame: 30 days
measure: Target Vessel Failure (TVF)
timeFrame: 180 days
measure: Target Vessel Failure (TVF)
timeFrame: 1 year
measure: Target Vessel Failure (TVF)
timeFrame: 2 year
measure: Target Vessel Failure (TVF)
timeFrame: 3 year
measure: Target Vessel Failure (TVF)
timeFrame: 4 year
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 30 days
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 180 days
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 270 days
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 1 years
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 2 years
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 3 year
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 4 year
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 30 days
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 180 days
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 270 days
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 1 year
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 2 years
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 3 years
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 4 years
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 30 days
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 180 days
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 270 days
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 1 year
measure: Ischemia Driven Major Adverse Cardiac Event(MACE)
timeFrame: 2 years
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 3 year
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 4 year
measure: In-stent % Angiographic Binary Restenosis (% ABR) Rate
timeFrame: at 240 days
measure: In-segment % Angiographic Binary Restenosis (% ABR) Rate
timeFrame: 240 days
measure: Persisting Incomplete Stent Apposition, Late-acquired Incomplete Stent Apposition, Aneurysm, Thrombosis, and Persisting Dissection
timeFrame: at 240 days
measure: Acute Success: Clinical Device
timeFrame: In-hospital
measure: Acute Success: Clinical Procedure
timeFrame: In-hospital
measure: Proximal Late Loss
timeFrame: at 240 days
measure: Distal Late Loss
timeFrame: 240 days
measure: In-stent Late Loss
timeFrame: at 240 days
measure: % Volume Obstruction (% VO)
timeFrame: at 240 days
measure: In-stent % Diameter Stenosis (% DS)
timeFrame: at 240 days
measure: In-segment % Diameter Stenosis (% DS)
timeFrame: 240 days
measure: Target Vessel Failure (TVF)
timeFrame: 5 years
measure: Ischemia Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 5 years
measure: Ischemia Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 5 years
measure: Ischemia Driven Major Adverse Cardiac Event (MACE)
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Baptist Medical Center Princeton
state: Alabama
city: Birmingham
country: United States
facility: Baptist Health System - Montclair
state: Alabama
city: Phoenix
country: United States
facility: Arizona Heart Hospital
state: Arizona
city: La Jolla
country: United States
facility: Scripps Memorial Hospital
state: California
city: Los Angeles
country: United States
facility: Good Samaritan Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Medical Center (prev. North Ridge MC)
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Elmhurst
country: United States
facility: Elmhurst Memorial Hospital
state: Illinois
city: Springfield
country: United States
facility: St. John's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: The Heart Center of IN, LLC
state: Indiana
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Takoma Park
country: United States
facility: Washington Adventist Hospital
state: Maryland
city: Towson
country: United States
facility: St. Joseph Medical Center
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: St John Hospital & Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: St. Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Missoula
country: United States
facility: St. Patrick Hospital
state: Montana
city: Lincoln
country: United States
facility: Nebraska Heart Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: Presbyterian Hospital
state: New Mexico
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: St. Joseph's Hospital Health Center
state: New York
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Elyria
country: United States
facility: EMH Regional Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Integris Baptist Medical, Inc.
state: Oklahoma
city: Eugene
country: United States
facility: Sacred Heart Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Harrisburg
country: United States
facility: Pinnacle Health @ Harrisburg Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Heart Hospital of Austin
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: TexSan Heart Hospital
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Columbia University
name: Gregg W Stone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Mahaffey KW, Cutlip DE, Fitzgerald PJ, Sood P, Su X, Lansky AJ; SPIRIT III Investigators. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA. 2008 Apr 23;299(16):1903-13. doi: 10.1001/jama.299.16.1903.
citation: Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Caputo R, Xenopoulos N, Applegate R, Gordon P, White RM, Sudhir K, Cutlip DE, Petersen JL; SPIRIT III Investigators. Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation. 2009 Feb 10;119(5):680-6. doi: 10.1161/CIRCULATIONAHA.108.803528. Epub 2009 Jan 26.
citation: Lansky AJ, Ng VG, Mutlu H, Cristea E, Guiran JB, Midei M, Newman W, Sanz M, Sood P, Doostzadeh J, Su X, White R, Cao S, Sudhir K, Stone GW. Gender-based evaluation of the XIENCE V everolimus-eluting coronary stent system: clinical and angiographic results from the SPIRIT III randomized trial. Catheter Cardiovasc Interv. 2009 Nov 1;74(5):719-27. doi: 10.1002/ccd.22067.
citation: Genereux P, Rutledge DR, Palmerini T, Caixeta A, Kedhi E, Hermiller JB, Wang J, Krucoff MW, Jones-McMeans J, Sudhir K, Simonton CA, Serruys PW, Stone GW. Stent Thrombosis and Dual Antiplatelet Therapy Interruption With Everolimus-Eluting Stents: Insights From the Xience V Coronary Stent System Trials. Circ Cardiovasc Interv. 2015 May;8(5):e001362. doi: 10.1161/CIRCINTERVENTIONS.114.001362.
citation: Muramatsu T, Onuma Y, van Geuns RJ, Chevalier B, Patel TM, Seth A, Diletti R, Garcia-Garcia HM, Dorange CC, Veldhof S, Cheong WF, Ozaki Y, Whitbourn R, Bartorelli A, Stone GW, Abizaid A, Serruys PW; ABSORB Cohort B Investigators; ABSORB EXTEND Investigators; SPIRIT FIRST Investigators; SPIRIT II Investigators; SPIRIT III Investigators; SPIRIT IV Investigators. 1-year clinical outcomes of diabetic patients treated with everolimus-eluting bioresorbable vascular scaffolds: a pooled analysis of the ABSORB and the SPIRIT trials. JACC Cardiovasc Interv. 2014 May;7(5):482-93. doi: 10.1016/j.jcin.2014.01.155. Epub 2014 Apr 16.
citation: Claessen BE, Smits PC, Kereiakes DJ, Parise H, Fahy M, Kedhi E, Serruys PW, Lansky AJ, Cristea E, Sudhir K, Sood P, Simonton CA, Stone GW. Impact of lesion length and vessel size on clinical outcomes after percutaneous coronary intervention with everolimus- versus paclitaxel-eluting stents pooled analysis from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice) Randomized Trials. JACC Cardiovasc Interv. 2011 Nov;4(11):1209-15. doi: 10.1016/j.jcin.2011.07.016.
citation: Planer D, Smits PC, Kereiakes DJ, Kedhi E, Fahy M, Xu K, Serruys PW, Stone GW. Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) Trials. JACC Cardiovasc Interv. 2011 Oct;4(10):1104-15. doi: 10.1016/j.jcin.2011.06.018.
citation: Kereiakes DJ, Sudhir K, Hermiller JB, Gordon PC, Ferguson J, Yaqub M, Sood P, Su X, Yakubov S, Lansky AJ, Stone GW. Comparison of everolimus-eluting and paclitaxel-eluting coronary stents in patients undergoing multilesion and multivessel intervention: the SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) and SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) randomized trials. JACC Cardiovasc Interv. 2010 Dec;3(12):1229-39. doi: 10.1016/j.jcin.2010.09.014.
citation: Caixeta A, Lansky AJ, Serruys PW, Hermiller JB, Ruygrok P, Onuma Y, Gordon P, Yaqub M, Miquel-Hebert K, Veldhof S, Sood P, Su X, Jonnavithula L, Sudhir K, Stone GW; SPIRIT II and III Investigators. Clinical follow-up 3 years after everolimus- and paclitaxel-eluting stents: a pooled analysis from the SPIRIT II (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) and SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) randomized trials. JACC Cardiovasc Interv. 2010 Dec;3(12):1220-8. doi: 10.1016/j.jcin.2010.07.017.