CYPRESS - CYPHER for Evaluating Sustained Safety

Coronary Artery Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00954707
• Other study ID #: P09-6301
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 6, 2009
• Last updated: January 13, 2014
• Start date: August 2009
• Est. completion date: March 2016

Study information

• Verified date: January 2014
• Source: Cordis Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2509
• Est. completion date: March 2016
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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:

1. The subject must be =18 years of age

2. Index procedure requiring use of a stent with a nominal diameter 2.25mm to 3.5mm

3. Lesion Length = 34mm

4. Up to 2 lesions in up to 2 vessels (2 in one vessel or 1 in each of 2 vessels)

5. Ejection fraction > 30%

6. Target lesion stenosis is >50% and <100% (visual estimate)

7. Female of childbearing potential must have a negative pregnancy test within 10 days prior to enrollment

8. 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:

1. Target Lesion includes Bifurcations with side branch diameter >2.5mm

2. Patient with excessive calcified/angulated lesion that is not suitable for stenting in the Investigator's opinion

3. Restenotic Target Lesion previously treated with a stent

4. Greater than 2 overlapping stents used to treat target lesion.

5. Target Lesion within an unprotected Left Main (LM) with =50% stenosis

6. Target Lesion within a coronary bypass graft (e.g., saphenous vein or arterial graft)

7. Chronic (> 3 months) Total Occlusion (CTO) Lesions, TIMI grade 0 or 1 in the target lesion

8. ST segment Elevation Myocardial Infarction (STEMI) within 30 days or non-STEMI within 72 hours

9. Renal insufficiency (creatinine >2.5 mg) or dialysis dependent

10. Lesion with visible clot

11. Patient with prior brachytherapy

12. Documented left ventricular ejection fraction is =30%

13. Pretreatment with devices other than conventional balloon angioplasty

14. Recipient of heart transplant

15. Subject with a life expectancy less than 1 year

16. 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);

17. Any significant medical condition which, in the Investigator's opinion, may interfere with the subject's optimal participation in the study;

18. 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

19. In the Investigator's opinion, the lesion is not suitable for stenting.

20. Known bleeding or hypercoagulable disorder;

21. Known or suspected active infection at the time of the study procedures;

22. Subject is known to be pregnant

23. Subject is a prisoner, mentally incompetent, and/or alcohol or drug abuser;

24. Planned (at the time of enrollment) surgery necessitating discontinuation of anti-platelet therapy within the twelve (12) months following enrollment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Clopidogrel & Aspirin, Prasugrel & 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 thienopyridine treatment in addition to aspirin.
• Placebo & 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.

Locations

Country	Name	City	State
United States	University Hospitals, Case Medical Center (Cleveland)	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Cordis Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 months	No
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.	From post- procedure to hospital discharge, up to 39 days	No
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.	From post- procedure to hospital discharge, up to 39 days	Yes
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.	From post- procedure to hospital discharge, up to 39 days	No
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.	12 Months	Yes
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.	12 months	Yes
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.	12 Months	Yes
Secondary	Rate of Major Adverse Cardiac Events (MACE)	MACE includes Death, myocardial infarction, emergent bypass surgery, or target lesion revascularization at 12 months	12 Months	Yes
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.	12 Months	Yes
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.	12 Months	Yes
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.	12 Months	Yes
Secondary	Rate of Cardiac Death	Include all deaths due to cardiac causes.	12 Months	Yes
Secondary	Rate of Non-cardiac Death	Include all deaths due to non-cardiac causes.	12 Months	Yes