CYPRESS - CYPHER for Evaluating Sustained Safety

Study Overview
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Brief Summary
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CYPRESS: A Prospective,Randomized,Multi-Center,Double-Blind Trial to Assess the Effectiveness and Safety of Different Durations of Dual Anti-Platelet Therapy (DAPT) in Subjects Undergoing Percutaneous Coronary Intervention with the CYPHER® Sirolimus-eluting Coronary Stent (CYPHER® Stent)

Detailed Description
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During Phase I (non-randomized phase) of this study, the primary objective is to assess the rate of target lesion failure in subjects implanted with the CYPHER® stent and receiving dual antiplatelet therapy for 12 months. During Phase II (randomized phase) of this study, the primary objective is to assess safety (major and minor bleeding), MACCE, and ST rates in subjects treated with dual antiplatelet therapy for 12 or 30 months following CYPHER® stent implantation. *Subjects treated with the CYPHER® 2.25mm stent will be followed through 60 months. **The last 500 patients enrolled will not be eligible for randomization.

Official Title
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A Prospective, Randomized, Multi-Center, Double-Blind Trial to Assess the Effectiveness and Safety of Different Durations of Dual Anti-Platelet Therapy (DAPT) in Subjects Undergoing Percutaneous Coronary Intervention With the CYPHER® Sirolimus-eluting Coronary Stent (CYPHER® Stent)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Clopidogrel & Aspirin, Prasugrel & Aspirin
* Drug: Placebo & Aspirin


Participation Criteria
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Eligibility Criteria
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DAPT Group - Inclusion Criteria: Phase I: Enrollment Inclusion Criteria Subjects must meet ALL of the following inclusion criteria to be enrolled in the study: The subject must be 18 years of age. Subjects undergoing percutaneous intervention with stent deployment Subjects without known contraindication to dual antiplatelet therapy for at least 30 months after enrollment and stent implantation. The subject or Legally Authorized Representative has consented to participate and has authorized the collection and release of his/her medical information by signing the Patient Informed Consent Form that is approved by the Institutional Review Board or Independent Ethics Committee. The informed consent will be valid for the duration of the trial or until the subject withdraws. DAPT Group Phase II: Randomization Inclusion Criterion at 12 months Subjects must meet the following criterion to be eligible for randomization in the study: Subject is 12 Month Clear DAPT Group - Exclusion Criteria: Phase I: Enrollment Exclusion Criteria Subjects will be excluded if ANY of the following exclusion criteria apply: Index procedure requiring use of a stent with a nominal diameter < 2.25 mm or > 3.5 mm. Pregnant women. Planned (at time of enrollment) surgery necessitating discontinuation of antiplatelet therapy within the 30 months following enrollment. Current medical condition with a life expectancy of less than 3 years. Concurrent enrollment in another device or drug study where the primary endpoint has not been reached or the device/drug might affect major endpoint outcomes in either Phase I or Phase II of the study. The subject may only be enrolled in the study once. Subjects on warfarin or similar anticoagulant therapy. Subjects with hypersensitivity or allergies to one of the drugs or components indicated in the Instructions for Use for the device implanted. Subjects unable to give informed consent. Subject treated with both DES and BMS during the index procedure. DAPT Group Phase II: Randomization Exclusion Criteria at 12 months Subjects will be excluded from randomization if any of the following criteria are met: Pregnant women. Subject switched thienopyridine type within 6 months prior to randomization Percutaneous coronary interventions or cardiac surgery between 6 weeks post index procedure and randomization. Planned surgery necessitating discontinuation of antiplatelet therapy within the 21 months following randomization. Current medical condition with a life expectancy of less than 3 years. Subjects on subsequent warfarin or similar anticoagulant therapy. Subjects who do not receive any CYPHER® Stent during the index procedure. Non-DAPT Group The following inclusion and exclusion criteria are for the Non-DAPT subjects. These criteria will be used to determine if the subject meets the near on-label definition Non-DAPT Group - Inclusion Criteria: Subjects must meet ALL of the following criteria to be enrolled in this study: The subject must be ≥18 years of age Index procedure requiring use of a stent with a nominal diameter 2.25mm to 3.5mm Lesion Length ≤ 34mm Up to 2 lesions in up to 2 vessels (2 in one vessel or 1 in each of 2 vessels) Ejection fraction > 30% Target lesion stenosis is >50% and <100% (visual estimate) Female of childbearing potential must have a negative pregnancy test within 10 days prior to enrollment The subject or Legally Authorized Representative has consented to participate and has authorized the collection and release of his/her medical information by signing the Patient Informed Consent Form Non-DAPT Group - Exclusion criteria And must NOT meet any of the following exclusion criteria: Target Lesion includes Bifurcations with side branch diameter >2.5mm Patient with excessive calcified/angulated lesion that is not suitable for stenting in the Investigator's opinion Restenotic Target Lesion previously treated with a stent Greater than 2 overlapping stents used to treat target lesion. Target Lesion within an unprotected Left Main (LM) with ≥50% stenosis Target Lesion within a coronary bypass graft (e.g., saphenous vein or arterial graft) Chronic (> 3 months) Total Occlusion (CTO) Lesions, TIMI grade 0 or 1 in the target lesion ST segment Elevation Myocardial Infarction (STEMI) within 30 days or non-STEMI within 72 hours Renal insufficiency (creatinine >2.5 mg) or dialysis dependent Lesion with visible clot Patient with prior brachytherapy Documented left ventricular ejection fraction is ≤30% Pretreatment with devices other than conventional balloon angioplasty Recipient of heart transplant Subject with a life expectancy less than 1 year Known allergies to the following: aspirin, all commercially available anti-platelet drugs heparin, stainless steel, contrast agent (that cannot be managed medically), or sirolimus (that cannot be managed medically); Any significant medical condition which, in the Investigator's opinion, may interfere with the subject's optimal participation in the study; Currently participating in an investigational drug or device study that has either not completed the primary endpoint where the prior study drug/device might affect this study's primary endpoint In the Investigator's opinion, the lesion is not suitable for stenting. Known bleeding or hypercoagulable disorder; Known or suspected active infection at the time of the study procedures; Subject is known to be pregnant Subject is a prisoner, mentally incompetent, and/or alcohol or drug abuser; Planned (at the time of enrollment) surgery necessitating discontinuation of anti-platelet therapy within the twelve (12) months following enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 12m DAPT Group<br> | Drug: Placebo & Aspirin<br>* This population consists of subjects enrolled in the study who are free from death, MI, stroke, repeat coronary revascularization, major bleeding, and ST 12 months after stent implantation and who are compliant with 12 months of dual antiplatelet therapy following stent implantation and who are subsequently randomized to receive 18 months of placebo treatment in addition to aspirin.<br>|
| Active Comparator: 30m DAPT Group<br> | Drug: Clopidogrel & Aspirin, Prasugrel & Aspirin<br>* This population consists of subjects enrolled in the study who are free from death, MI, stroke, repeat coronary revascularization, major bleeding, and ST 12 months after stent implantation and who are compliant with 12 months of dual antiplatelet therapy following stent implantation and who are subsequently randomized to receive 18 months of thienopyridine treatment in addition to aspirin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: the Rate of Target Lesion Failure (TLF) | Target lesion failure (TLF) is defined as clinically-driven target lesion revascularization, target vessel myocardial infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel at 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Device Success | A study device success is defined as achievement of a final residual diameter stenosis of < 50% (by QCA), using the assigned device only. If QCA is not available, the visual estimate of diameter stenosis is used. | From post- procedure to hospital discharge, up to 39 days | 
| Rate of Lesion Success | Lesion success is defined as the attainment of < 50% residual stenosis (by Quantitative coronary angiography (QCA)) using any percutaneous method. | From post- procedure to hospital discharge, up to 39 days | 
| Rate of Procedure Success | Procedure success is defined as the achievement of a final diameter stenosis of < 50% (by QCA) using any percutaneous method, without the occurrence of death, Myocardial infarction (MI), or repeat coronary revascularization of the target lesion during the hospital stay. | From post- procedure to hospital discharge, up to 39 days | 
| Rate of Clinically-driven Target Lesion Revascularization (TVR) | Defined as any clinically-driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel. Clinically-driven revascularizations are those in which the subject has a positive functional study, ischemic ECG changes at rest in a distribution consistent with the target vessel, or ischemic symptoms, and an in-lesion diameter stenosis ≥50% by QCA. | 12 Months | 
| Rate of Clinically Driven Target Vessel Revascularization (TVR) | Defined as any clinically driven repeat percutaneous intervention of the target vessel or bypass surgery of the target vessel. Clinically-driven revascularizations are those in which the subject has a positive functional study, ischemic ECG changes at rest in a distribution consistent with the target vessel, or ischemic symptoms, and an in-lesion diameter stenosis ≥50% by QCA. | 12 months | 
| Rate of Target Vessel Failure (TVF) | Defined as target vessel revascularization, recurrent infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel. | 12 Months | 
| Rate of Major Adverse Cardiac Events (MACE) | MACE includes Death, myocardial infarction, emergent bypass surgery, or target lesion revascularization at 12 months | 12 Months | 
| Rate of Protocol Defined Stent Thrombosis (ST) | Protocol defined ST includes early and late ST. Early thrombosis is defined as composite thirty-day ischemic endpoint including death, Q-wave myocardial infarction, or subabrupt closure requiring revascularization. Late thrombosis is defined as myocardial infarction occurring > 30 days after the index procedure and attributable to the target vessel with angiographic documentation (site reported or by qualitative coronary angiography) of thrombus or total occlusion at the target site and freedom from an interim revascularization of the target vessel. | 12 Months | 
| Rate of Academic Research Consortium (ARC) Defined Stent Thrombosis (ST) | ARC defined ST classifies ST by type - definite, probable, possible; by timing - acute, sub-acute, late, very late. Definite includes angiographic or pathologic confirmation; probable includes Any unexplained death within the first 30 days or Any MI (related to documented acute ischemia and without another obvious cause) in the territory of the stent; Possible includes Any unexplained death > 30 days. Acute includes those ≤ 24 hours post procedure; sub-acute includes those > 24 hours to ≤ 30 days post procedure; and late includes those > 30 days to ≤ 1 year post procedure; and very late includes those > 1 year post procedure. | 12 Months | 
| Rate of Protocol Defined Major Bleeding Complications | Defined by the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification, including severe and moderate bleeding combined. | 12 Months | 
| Rate of Cardiac Death | Include all deaths due to cardiac causes. | 12 Months | 
| Rate of Non-cardiac Death | Include all deaths due to non-cardiac causes. | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerosis