SPIRIT V: A Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Coronary Artery Lesions (Diabetic Sub-Study)

SPIRIT V: A Clinical Evaluation of the XIENCE V® Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Coronary Artery Lesions

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01171820

Enrollment

324

Registered

2010-07-29

Start date

2006-11-30

Completion date

2010-07-31

Last updated

2016-06-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease, Coronary Disease, Coronary Restenosis

Keywords

drug eluting stents, stents, Angioplasty, coronary artery disease, total coronary occlusion, coronary artery restenosis, stent thrombosis, vascular disease, myocardial ischemia, coronary artery stenosis

Brief summary

The purpose of this Clinical Evaluation is a continuation in the assessment of the performance of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) in the treatment of patients with de novo coronary artery lesions in patients (Diabetic sub-study).

Detailed description

The SPIRIT V Clinical Evaluation consists of two concurrent studies,the Diabetic sub-study and the Registry. The SPIRIT V Diabetic sub-study is a prospective, randomized, active-controlled, single blind, parallel two-arm multi-center study comparing the XIENCE V® EECSS to the TAXUS® Liberté™ in the treatment of diabetic patients with coronary artery lesions who will fulfill the eligibility criteria. Approximately 300 patients will be randomized (2:1) against the TAXUS® Liberté™ coronary stent system. These patients will be recruited in up to 40 selected sites. The long term safety and efficacy of the XIENCE V EECSS have been demonstrated in the SPIRIT FIRST trial up to 5 years, the SPIRIT II trial up to 4 years, and in the SPIRIT III Randomized Control Trial (RCT) up to 3 years. In addition, these pre-approval studies have shown low rates of Target Vessel Failure and Major Adverse Cardiac Events (MACE) that were observed to plateau or gradually decline after about 1 year and were consistently lower than the comparator arm of each study. This benefit in MACE is sustained for up to 5 years and is also independent of the first year results. The post approval SPIRIT V study demonstrated that the use of the XIENCE EECSS in complex lesions in a real-world population resulted in 1 year MACE, Stent Thrombosis and Target Lesion Revascularization rates that are comparable to those of the previously mentioned pre-approval studies which included patients with more restricted inclusion / exclusion criteria. Therefore, based on existing data from these trials, Abbott Vascular has decided to discontinue further follow up in the SPIRIT V Diabetic study after 1 year.

Interventions

DEVICETAXUS® Liberté™

Drug eluting stent implantation stent in the treatment of coronary artery disease in participants with Diabetes

DEVICEXIENCE V® EECSS

Drug eluting stent implantation stent in the treatment of coronary artery disease in participants with Diabetes

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* at least 18 years * able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the XIENCE V® EECSS and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure, as approved by the appropriate Medical Ethics Committee of the respective clinical site * diagnosed with diabetes, as documented by medical history. * evidence of myocardial ischemia * acceptable candidate for coronary artery bypass grafting (CABG) surgery * agree to undergo all clinical investigation plan (CIP)-required follow-up examinations * artery morphology and disease is suitable to be optimally treated with a maximum of 4 planned stents * maximum of one, de novo, target lesion per native major epicardial vessel or side branch * target vessel reference diameter must be between 2.25 mm and 4.0 mm by visual estimate * target lesion ≤ 28 mm in length by visual estimate * target lesion must be in a major artery or branch with a visually estimated stenosis of \> 50% and \< 100% and a TIMI flow \> 1

Exclusion criteria

* known diagnosis of acute myocardial infarction within 72 hours preceding the index procedure * current unstable arrhythmias * Left ventricular ejection fraction \< 30% * received a heart or any other organ transplant or is on a waiting list for any organ transplant * receiving or scheduled to receive chemotherapy or radiation therapy within 30 days prior to or after the procedure. * receiving immunosuppression therapy or has known immunosuppressive or autoimmune disease * known hypersensitivity or contraindication to specific agents * elective surgery is planned within the first 9 months after the procedure that will require discontinuing either aspirin or clopidogrel * platelet count limits, white blood cell limits or documented or suspected liver disease * renal insufficiency * history of bleeding diathesis or coagulopathy or will refuse blood transfusions * Cerebrovascular accident or transient ischemic attack within the past 6 months * significant GI or urinary bleed within the past 6 months * history of other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse that may cause non-compliance with the CIP, confound the data interpretation or is associated with a limited life expectancy (i.e. less than one year) Target lesion meets any of the following criteria: * In-stent restenotic * aorto-ostial location (within 3 mm) * left main location * located within 2 mm of the origin of the left anterior descending artery (LAD) or left circumflex artery (LCX) * located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft (defined as vessel irregularity per angiogram and \> 20% stenosed lesion by visual estimation) * lesion involving a side branch ≥ 2.5 mm in diameter * lesion involving a side branch with \> 50% stenosis by visual estimation Lesion involving a side branch requiring predilatation * located in a major epicardial vessel that has been previously treated with brachytherapy * located in a major epicardial vessel or a side branch that has been previously treated with any type of percutaneous intervention (e.g., balloon angioplasty, cutting balloon, atherectomy), \< 9 months prior to the index procedure * total occlusion (TIMI flow 0), prior to wire crossing * excessive tortuosity proximal to or within the lesion * extreme angulation (≥ 90%) proximal to or within the lesion * heavy calcification The target vessel contains visible thrombus Patient has a high probability that a procedure other than pre-dilatation, stenting and post-dilatation will be required at the time of index procedure for treatment of the target vessel (e.g. brachytherapy) Patient has additional clinically significant lesion(s) (\> 50% diameter stenosis) in a target vessel or side branch for which an intervention within 9 months after the index procedure may be required

Design outcomes

Primary

Measure	Time frame	Description
In-stent Late Loss (LL)	270 days	In-stent minimal lumen diameter (MLD) post-procedure minus (-) in-stent MLD at follow-up

Secondary

Measure	Time frame	Description
Clinical Procedure Success (Per-patient)	immediately post-procedure	Successful delivery and deployment of the study stent or stents at the intended target lesion and successful withdrawal of the stent delivery system with attainment of final residual stenosis of less than 50% of the target lesion by quantitative coronary angiography (QCA) (by visual estimation if QCA unavailable) and/or using any adjunctive device without the occurrence of cardiac death, MI attributed to the target vessel and/or CI-TLR during the hospital stay with a maximum of first seven days post index procedure. In multiple lesion setting each lesion must meet clinical procedure success.
In-segment Late Loss	270 days	In-segment minimal lumen diameter (MLD) post-procedure minus (-) in segment MLD at follow-up
Proximal Late Loss	270 day	Proximal Minimum Lumen Diameter (MLD) post-procedure minus proximal MLD at follow-up
Distal Late Loss	270 days	Distal Minimum Lumen Diameter (MLD) post-procedure minus distal MLD at follow-up
In-stent Angiographic Binary Restenosis Rate	270 days	Percent of patients with a follow-up percent diameter stenosis of ≥ 50% per QCA.
In-segment Angiographic Binary Restenosis Rate	270 days	Percent of patients with a follow-up percent diameter stenosis of ≥ 50% per QCA.
In-stent Percent Diameter Stenosis (% DS)	270 days	This number represents the average of percent diameter stenosis found on examination of all the lesions analyzed. This value calculated as 100 \* (1 - minimum lumen diameter/reference vessel diameter) (MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA.
Clinical Device Success (Per-lesion)	immediately post-procedure	Successful delivery and deployment of the study stent (in overlapping stent setting a successful delivery and deployment of the first and second study stent) at the intended target lesion and successful withdrawal of the stent delivery system with attainment of final residual stenosis of less than 50% of the target lesion by quantitative coronary angiography (QCA) (by visual estimation if QCA unavailable), without use of a device outside the assigned treatment strategy.
Adjudicated Stent Thrombosis (Confirmed/Definite, Probable, Possible)	0 to 37 days	The Clinical Event Committee will adjudicate the events according to the definitions developed by the Academic Research Consortium (ARC), as published in Circulation (Cutlip, D.E., et al., Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation, 2007. 115: p. 2344-2351.) Stent thrombosis was defined according to the ARC guidelines as follows: definite: acute coronary syndrome and angiographic or pathological confirmation of stent thrombosis; probable: unexplained death ≤30 days or any MI that is related to acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis; and possible: unexplained death \>30 days after stent placement.
Adjudicated Revascularizations (Target Lesion Revascularization (TLR)/ Target Vessel Revascularization (TVR)/Any Revascularization) Both Clinically-indicated and Not Clinically-indicated.	37 days	TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. The target lesion was defined as the treated segment from 5 mm proximal and 5 mm distal to the stent. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel was defined as the entire major coronary vessel proximal and distal to the target lesion, including upstream and downstream branches and the target lesion itself. A revascularization is considered clinically indicated if angiography at follow-up shows a %DS ≥ 50% and if one of the following occurs: history of recurrent angina pectoris due to the target vessel; signs of ischemia at rest or during exercise test due to target vessel; abnormal results of any invasive diagnostic test; TLR or TVR with a % DS ≥ 70% even in the absence of the above mentioned ischemic signs.
Adjudicated Composite Endpoint of Cardiac Death, Myocardial Infarction (MI) Attributed to the Target Vessel and Clinical-indicated Target Lesion Revascularization (CI-TLR)	37 days	Cardiac death: Any death due to proximate cardiac cause (eg, myocardial infarction, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure related deaths, including those related to concomitant treatment, will be classified as cardiac death. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Clinical-indicated Target Lesion Revascularization (CI-TLR): TLR with evidence of diameter stenosis ≥ 50% determined by QCA; or in the case of any one of the following: new recurrent history of angina pectoris, ischemic signs, abnormal results in diagnostic tests, or TLR \>=70% in the absence of the above signs.
Adjudicated Composite Endpoint of All Death, MI and Target Vessel Revascularization (TVR)	37 days	Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. Specifically, any unexpected death even in patients with coexisting potentially fatal noncardiac disease (eg, cancer, infection) should be classified as cardiac. Myocardial infarction: Myocardial Infarction Classification and Criteria for Diagnosis as defined by the Academic Research Consortium. Target Vessel Revascularization (TVR): Target vessel revascularization is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion, which includes upstream and downstream branches and the target lesion itself.
Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non-TVR)	37 days	Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR
Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non TVR)	254 days	Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR
In-segment Percent Diameter Stenosis (% DS)	270 days	This number represents the average of percent diameter stenosis found on examination of all the lesions analyzed. This value calculated as 100 \* (1 - MLD/RVD) using the mean values from two orthogonal views (when possible) by QCA.

Countries

Austria, France, Germany, Israel, Italy, Malaysia, Netherlands, Poland, Spain, Thailand, United Kingdom

Participant flow

Recruitment details

324 subjects were recruited at 32 sites. Eligible subjects invited to participate, in-hospital or in-clinic and required to provide signed informed consent prior to enrollment. Final eligibility based on angiographic inclusion criteria prior to the intended procedure. Dates of recruitment: April 28, 2007 to October 6, 2008.

Pre-assignment details

Subjects were randomized via telephone randomization and stratified by insulin treatment status, number of lesions treated-single vs. multiple. Randomization only occurred after verification of the inclusion/exclusion criteria and successful pre-dilatation. See the Eligibility Criteria (inclusion/exclusion criteria) for details.

Participants by arm

Arm	Count
TAXUS® Liberté™ Patients receiving the TAXUS® Liberté™ stent during PCI	106
XIENCE V® EECSS Patients receiving the XIENCE V® EECSS stent during PCI	218
Total	324

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	1-Year Missed Visit	1	1
Overall Study	Death	3	3
Overall Study	Lost to Follow-up	0	1
Overall Study	Physician Decision	0	1
Overall Study	Withdrawal by Subject	2	0

Baseline characteristics

Characteristic	TAXUS® Liberté™	XIENCE V® EECSS	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	57 Participants	116 Participants	173 Participants
Age, Categorical Between 18 and 65 years	49 Participants	102 Participants	151 Participants
Age, Continuous	65.75 years STANDARD_DEVIATION 8.95	65.32 years STANDARD_DEVIATION 9.61	65.46 years STANDARD_DEVIATION 9.39
Region of Enrollment Austria	2 participants	8 participants	10 participants
Region of Enrollment France	2 participants	7 participants	9 participants
Region of Enrollment Germany	14 participants	22 participants	36 participants
Region of Enrollment Israel	1 participants	1 participants	2 participants
Region of Enrollment Italy	17 participants	43 participants	60 participants
Region of Enrollment Malaysia	1 participants	13 participants	14 participants
Region of Enrollment Netherlands	1 participants	12 participants	13 participants
Region of Enrollment Poland	8 participants	17 participants	25 participants
Region of Enrollment Spain	57 participants	87 participants	144 participants
Region of Enrollment Thailand	0 participants	2 participants	2 participants
Region of Enrollment United Kingdom	3 participants	6 participants	9 participants
Sex: Female, Male Female	35 Participants	66 Participants	101 Participants
Sex: Female, Male Male	71 Participants	152 Participants	223 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	13 / 105	26 / 215
serious Total, serious adverse events	41 / 105	100 / 215

Outcome results

Primary

In-stent Late Loss (LL)

In-stent minimal lumen diameter (MLD) post-procedure minus (-) in-stent MLD at follow-up

Time frame: 270 days

Population: Analysis based on intention to treat (ITT) population. Patients were required to have angiographic follow-up to provide this endpoint information. Some patients not completing the study, did not have this follow up.

Arm	Measure	Value (MEAN)	Dispersion
TAXUS® Liberté™	In-stent Late Loss (LL)	0.39 millimeters	Standard Deviation 0.49
XIENCE V® EECSS	In-stent Late Loss (LL)	0.19 millimeters	Standard Deviation 0.37

Secondary

Adjudicated Composite Endpoint of All Death, Any Myocardial Infarction (MI) and Any Revascularization (TLR/TVR/Non TVR)

Death defined by the Academic Research Consortium is as follows: All death is considered to be cardiac death unless an unequivocal noncardiac cause can be established. MI- due to target vessel: All infarcts that cannot be clearly attributed to a vessel other than the target vessel will be considered related to the target vessel. Any revascularization: TLR or TVR or non-TVR

Time frame: 393 days