Trial Outcomes & Findings for CYPRESS - CYPHER for Evaluating Sustained Safety (NCT NCT00954707)

Results Overview

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.

Recruitment status

UNKNOWN

Study phase

PHASE4

Target enrollment

2509 participants

Primary outcome timeframe

12 months

Results posted on

2014-02-07

Participant Flow

A total of 2509 patients were enrolled from August 28, 2009 to January 14, 2011 across 139 clinical sites in the Unites States.

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.

Participant milestones

Participant milestones
Measure	All Enrolled Subjects Subjects signed the consent forms and met all protocol defined inclusion criteria and none of the exclusion criteria.
Overall Study STARTED	2509
Overall Study COMPLETED	2342
Overall Study NOT COMPLETED	167

Reasons for withdrawal

Reasons for withdrawal
Measure	All Enrolled Subjects Subjects signed the consent forms and met all protocol defined inclusion criteria and none of the exclusion criteria.
Overall Study Death	34
Overall Study Withdrawal by Subject	100
Overall Study Lost to Follow-up	33

Baseline Characteristics

CYPRESS - CYPHER for Evaluating Sustained Safety

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CYPHER® Stent n=2509 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1368 Participants n=5 Participants
Age, Categorical >=65 years	1141 Participants n=5 Participants
Age, Continuous	63.26 years STANDARD_DEVIATION 10.64 • n=5 Participants
Sex: Female, Male Female	785 Participants n=5 Participants
Sex: Female, Male Male	1724 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2293 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	84 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	6 Participants n=5 Participants
Race (NIH/OMB) Black or African American	185 Participants n=5 Participants
Race (NIH/OMB) White	2225 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	50 Participants n=5 Participants
Region of Enrollment United States	2509 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Active subjects in the ITT population at 12-month post procedure

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2322 Participants 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.
Phase I: the Rate of Target Lesion Failure (TLF)	149 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=3271 Devices 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.
Rate of Device Success	3205 Devices

SECONDARY outcome

Timeframe: 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

Lesion success is defined as the attainment of \< 50% residual stenosis (by Quantitative coronary angiography (QCA)) using any percutaneous method.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=3271 Lesions 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.
Rate of Lesion Success	3264 Lesions

SECONDARY outcome

Timeframe: From post- procedure to hospital discharge, up to 39 days

Population: Intent-to-Treat Population

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2509 Participants 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.
Rate of Procedure Success	2444 participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2318 Participants 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.
Rate of Clinically-driven Target Lesion Revascularization (TVR)	98 participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2318 Participants 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.
Rate of Clinically Driven Target Vessel Revascularization (TVR)	124 participants

SECONDARY outcome

Timeframe: 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).

Defined as target vessel revascularization, recurrent infarction, or cardiac death that could not be clearly attributed to a vessel other than the target vessel.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2323 Participants 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.
Rate of Target Vessel Failure (TVF)	184 participants

SECONDARY outcome

Timeframe: 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).

MACE includes Death, myocardial infarction, emergent bypass surgery, or target lesion revascularization at 12 months

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2322 Participants 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.
Rate of Major Adverse Cardiac Events (MACE)	172 participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2313 Participants 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.
Rate of Protocol Defined Stent Thrombosis (ST)	21 participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2313 Participants 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.
Rate of Academic Research Consortium (ARC) Defined Stent Thrombosis (ST)	26 participants

SECONDARY outcome

Timeframe: 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)

Defined by the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification, including severe and moderate bleeding combined.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2314 Participants 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.
Rate of Protocol Defined Major Bleeding Complications	71 participants

SECONDARY outcome

Timeframe: 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)

Include all deaths due to cardiac causes.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2313 Participants 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.
Rate of Cardiac Death	18 participants

SECONDARY outcome

Timeframe: 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)

Include all deaths due to non-cardiac causes.

Outcome measures

Outcome measures
Measure	CYPHER® Stent n=2313 Participants 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.
Rate of Non-cardiac Death	16 participants

Adverse Events

CYPHER® Stent

Serious events: 34 serious events

Other events: 414 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CYPHER® Stent n=2509 participants at risk 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.
Cardiac disorders Cardiac Death	0.72% 18/2509 • Number of events 18
General disorders Non-cardiac death	0.64% 16/2509 • Number of events 16

Other adverse events

Other adverse events
Measure	CYPHER® Stent n=2509 participants at risk 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.
Cardiac disorders Angina pectoris	4.3% 108/2509 • Number of events 150
Cardiac disorders Angina unstable	2.1% 53/2509 • Number of events 77
Cardiac disorders Coronary artery disease	1.7% 43/2509 • Number of events 64
Cardiac disorders Coronary artery occlusion	1.2% 31/2509 • Number of events 34
Cardiac disorders Myocardial infarction	3.0% 76/2509 • Number of events 99
General disorders Catheter site haematoma	1.6% 39/2509 • Number of events 40
Injury, poisoning and procedural complications In-stent coronary artery restenosis	1.1% 28/2509 • Number of events 46
Investigations Cardiac enzymes increased	1.0% 26/2509 • Number of events 28
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 27/2509 • Number of events 30
Cardiac disorders Coronary artery dissection	3.1% 79/2509 • Number of events 80

Additional Information

Amy Orlick, Associate Director

Cordis Corporation, a Johnson & Johnson company

Phone: 908-541-4347

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60