Coronary Artery Disease
Conditions
Keywords
Atherosclerosis
Brief summary
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
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.
Interventions
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.
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.
Sponsors
Cordis US Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: the Rate of Target Lesion Failure (TLF) | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Lesion Success | From post- procedure to hospital discharge, up to 39 days | Lesion success is defined as the attainment of \< 50% residual stenosis (by Quantitative coronary angiography (QCA)) using any percutaneous method. |
| Rate of Procedure Success | From post- procedure to hospital discharge, up to 39 days | 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. |
| Rate of Clinically-driven Target Lesion Revascularization (TVR) | 12 Months | 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. |
| Rate of Clinically Driven Target Vessel Revascularization (TVR) | 12 months | 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. |
| Rate of Target Vessel Failure (TVF) | 12 Months | Defined as target vessel revascularization, recurrent infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel. |
| Rate of Device Success | From post- procedure to hospital discharge, up to 39 days | 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. |
| Rate of Protocol Defined Stent Thrombosis (ST) | 12 Months | 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. |
| Rate of Academic Research Consortium (ARC) Defined Stent Thrombosis (ST) | 12 Months | 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. |
| Rate of Protocol Defined Major Bleeding Complications | 12 Months | Defined by the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification, including severe and moderate bleeding combined. |
| Rate of Cardiac Death | 12 Months | Include all deaths due to cardiac causes. |
| Rate of Non-cardiac Death | 12 Months | Include all deaths due to non-cardiac causes. |
| Rate of Major Adverse Cardiac Events (MACE) | 12 Months | MACE includes Death, myocardial infarction, emergent bypass surgery, or target lesion revascularization at 12 months |
Countries
United States
Participant flow
Recruitment details
A total of 2509 patients were enrolled from August 28, 2009 to January 14, 2011 across 139 clinical sites in the Unites States.
Pre-assignment details
During the Phase I of this study, enrolled subjects were treated with at least one CYPHER® stent plus thienopyridine treatment and aspirin. During Phase II, approximately 1500 eligible subjects were randomized to either placebo or thienopyridine treatment. It is estimated that the Phase II results will be available for publishing by July 31, 2014.
Participants by arm
| Arm | Count |
|---|---|
| CYPHER® Stent The CYPHER® Sirolimus-eluting Coronary Stent is a BX Velocity stent design and is laser cut from 316L stainless steel seamless tubing and electropolished. The stent design is intended to balance radial strength and closed cell architecture with longitudinal flexibility in both unexpanded and expanded forms. The design can be broken into two distinct components: the radial expansion ring segments and the flexible connectors in an alternating fashion. | 2,509 |
| Total | 2,509 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 34 |
| Overall Study | Lost to Follow-up | 33 |
| Overall Study | Withdrawal by Subject | 100 |
Baseline characteristics
| Characteristic | CYPHER® Stent |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1141 Participants |
| Age, Categorical Between 18 and 65 years | 1368 Participants |
| Age, Continuous | 63.26 years STANDARD_DEVIATION 10.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 132 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2293 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 84 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants |
| Race (NIH/OMB) Asian | 37 Participants |
| Race (NIH/OMB) Black or African American | 185 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 50 Participants |
| Race (NIH/OMB) White | 2225 Participants |
| Region of Enrollment United States | 2509 participants |
| Sex: Female, Male Female | 785 Participants |
| Sex: Female, Male Male | 1724 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 414 / 2,509 |
| serious Total, serious adverse events | 34 / 2,509 |
Outcome results
Primary
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.
Time frame: 12 months
Population: Active subjects in the ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Phase I: the Rate of Target Lesion Failure (TLF) | 149 participants |
95% CI: [5.5, 7.5]
Secondary
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.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Academic Research Consortium (ARC) Defined Stent Thrombosis (ST) | 26 participants |
95% CI: [0.74, 1.64]
Secondary
Rate of Cardiac Death
Include all deaths due to cardiac causes.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Cardiac Death | 18 participants |
95% CI: [0.46, 1.23]
Secondary
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.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Clinically-driven Target Lesion Revascularization (TVR) | 98 participants |
95% CI: [3.45, 5.13]
Secondary
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.
Time frame: 12 months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Clinically Driven Target Vessel Revascularization (TVR) | 124 participants |
95% CI: [4.87, 6.81]
Secondary
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.
Time frame: From post- procedure to hospital discharge, up to 39 days
Population: The total number of devices the Intent-to-Treat patients used in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Device Success | 3205 Devices |
95% CI: [97.4, 98.4]
Secondary
Rate of Lesion Success
Lesion success is defined as the attainment of \< 50% residual stenosis (by Quantitative coronary angiography (QCA)) using any percutaneous method.
Time frame: From post- procedure to hospital discharge, up to 39 days
Population: The total number of lesions the Intent-to-Treat population had at the beginning of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Lesion Success | 3264 Lesions |
95% CI: [99.6, 99.9]
Secondary
Rate of Major Adverse Cardiac Events (MACE)
MACE includes Death, myocardial infarction, emergent bypass surgery, or target lesion revascularization at 12 months
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Major Adverse Cardiac Events (MACE) | 172 participants |
95% CI: [6.37, 8.55]
Secondary
Rate of Non-cardiac Death
Include all deaths due to non-cardiac causes.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Non-cardiac Death | 16 participants |
95% CI: [0.4, 1.12]
Secondary
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.
Time frame: From post- procedure to hospital discharge, up to 39 days
Population: Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Procedure Success | 2444 participants |
95% CI: [97, 98.2]
Secondary
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.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Protocol Defined Major Bleeding Complications | 71 participants |
95% CI: [2.4, 3.85]
Secondary
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.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Protocol Defined Stent Thrombosis (ST) | 21 participants |
95% CI: [0.56, 1.38]
Secondary
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.
Time frame: 12 Months
Population: ITT Population patients with the specific event prior to end of follow-up plus patients without that event but with death or adequate follow-up (within 1 month prior to end of scheduled 12 months follow-up).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYPHER® Stent | Rate of Target Vessel Failure (TVF) | 184 participants |
95% CI: [6.85, 9.09]