Coronary Artery Disease, Autosomal Dominant, 1
Conditions
Brief summary
In order to expand safety information in patients treated with the Endeavor Drug Eluting Stent System, or next generation model, a Continued Access (CA) study is added to the PROTECT Trial. The amended study is PROTECT CONTINUED ACCESS (PROTECT CA).
Detailed description
This was a prospective, multicenter, non-randomized, single-arm, open-label post market surveillance study designed to expand safety information in patients treated with the Endeavor® Zotarolimus Eluting Coronary Stent System. Since their introduction, Drug Eluting Stents (DES) have markedly decreased stent restenosis and the clinical need for repeat revascularization frequently observed with bare metal stents (BMS)1-10. However, the widespread use of DES has raised concerns regarding the occurrence of late stent thrombosis (\> 30 days after stent implantation)12-14. Although the incidence might seem low (0.2-0.7%)13,15-18 the high mortality and morbidity associated with stent thrombosis, and the soaring number of stents implanted annually, make it a significant medical problem. The purpose of this trial was to investigate the long-term clinical safety and efficacy of the Endeavor drug eluting stent in a large and higher risk patient population, which more closely reflects clinical practice today. Both unstable and stable patients with single or multivessel disease and complex lesions were eligible for enrollment. The selected primary endpoint was stent thrombosis, defined as definite and probable stent thrombosis according to the ARC definition, at 3 years. The main secondary endpoints were the composite of death or cardiac death combined with large or all non-fatal myocardial infarction, which are the typical clinical manifestations of stent thrombosis. These events are adjudicated by a clinical events committee. 1.2 Study Endpoints 1.2.1 Primary Endpoint: The overall stent thrombosis rate defined as definite and probable stent thrombosis according to the ARC definition at 3 years 1.2.2 Secondary Endpoints: Main Secondary Endpoints include: * Composite endpoint of total death and number of patients with all non-fatal myocardial infarction at 3 years * Composite endpoint of cardiac death and number of patients with all non-fatal myocardial infarction at 3 years * Composite endpoint of total death and number of patients with large non-fatal myocardial infarction at 3 years * Composite endpoint of cardiac death and number of patients with large non-fatal myocardial infarction at 3 years Additional secondary endpoints include: * Total Death and subcategories of Death * Large and all Myocardial Infarction (MI) * Stent thrombosis defined as definite, probable and possible * Composite score of clinical outcomes (death, myocardial infarction, stroke and revascularization) \* * Major Adverse Cardiac and Cerebral Events (MACCE) * Stroke (hemorrhagic in nature while on clopidogrel) * Bleeding complications in general * Target lesion revascularization (TLR) * Target vessel revascularization (TVR) * Non target vessel revascularization (non TVR) * Procedural success * Device success * Lesion success * Endpoints will be calculated at the follow-up time points and for the mean follow-up period. * The composite score of clinical outcomes (death, myocardial infarction, stroke and revascularization) constructed from a patient population according to the Delphi method.
Interventions
DEVICEEndeavor® Zotarolimus Eluting Coronary Stent System
Endeavor® Zotarolimus Eluting Coronary Stent System in a patient population requiring stent implantation
Sponsors
Medtronic Vascular
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is \> 18 years of age (or minimum age as required by local regulations). 2. The patient or patient's legal representative has consented to participate and has authorized the collection and release of his medical information by signing the Patient Informed Consent Form. 3. All lesions requiring interventions (target lesions - one to a maximum of four) in one or more native coronary arteries are amendable for implantation of one or more Endeavor® Zotarolimus Eluting Coronary Stent System. 4. Patient indication, lesion length and vessel diameter of the target lesion(s) are according to the 'Indications for Use' as mentioned in the 'Instructions for Use' that comes with every Endeavor® Zotarolimus Eluting Coronary Stent System. Please check the 'Instructions for Use' that comes with the product. Please be aware that the 'Instructions for Use' may be subject to change during the course of the study. 5 The patient is willing and able to cooperate with study procedures and required follow up visits.
Exclusion criteria
1. Women with known pregnancy or who are lactating. 2. Planned elective surgery necessitating discontinuation of clopidogrel within the regular planned period of clopidogrel administration. 3. Patients expected not to be compliant with the anti-platelet and/or anticoagulation therapy regimen. 4. Previous brachytherapy. 5. Previous implantation of a drug eluting stent. 6. Previous implantation of a bare metal stent in the preceding year. 7. Simultaneous or planned intervention other non cardiac vessels including but not limited to renal artery or carotid artery. 8. Current medical condition with a life expectancy of less than 3 years. 9. Manifest acute severe heart failure (Killip class III-IV). 10. The patient is currently, and during the first 3 years of the PROTECT trial, participating in another investigational device or drug study that clinically interferes with the PROTECT-study endpoints; or requires coronary angiography or other coronary artery imaging procedures. The patient may only be enrolled in the PROTECT-study once. 11. Patients with medical conditions that preclude the follow-up as defined in the protocol or that otherwise limits participation in this study. 12. Patients on warfarin or similar anti-coagulant therapy. 13. Patients with hypersensitivity or allergies to one of the drugs or components indicated in the Instructions for Use. 14. Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon. 15. Patients in whom anti-platelet and/or anticoagulation therapy is contraindicated. 16 Transplant patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Overall Stent Thrombosis Rate of the Endeavor® Zotarolimus Eluting Coronary Stent System in a Patient Population Requiring Stent Implantation | 3 years | The primary endpoint rate of ARC-defined definite or probable stent thrombosis at 3 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions. | 3 years | Total death and and number of patients with all non-fatal myocardial infarction. Cardiac death and number of patients with all non-fatal myocardial infarction. Total death and number of patients with large non-fatal myocardial infarction. Cardiac death and number of patients with large non-fatal myocardial infarction. |
Countries
United States
Participant flow
Recruitment details
1018 patients were enrolled from February 2009 until November 2009 in 48 participating hospitals in USA.
Pre-assignment details
Subjects were excluded from participation if they did not meet inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Endeavor® Zotarolimus Eluting Coronary Stent System Endeavor® Zotarolimus Eluting Coronary Stent Implantation in a patient population requiring stent implantation. | 1,018 |
| Total | 1,018 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 56 |
| Overall Study | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | Endeavor® Zotarolimus Eluting Coronary Stent System |
|---|---|
| Age, Continuous | 63.16 Years |
| Region of Enrollment United States | 1018 participants |
| Sex: Female, Male Female | 274 Participants |
| Sex: Female, Male Male | 744 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 134 / 1,018 |
| serious Total, serious adverse events | 415 / 1,018 |
Outcome results
Primary
To Evaluate Overall Stent Thrombosis Rate of the Endeavor® Zotarolimus Eluting Coronary Stent System in a Patient Population Requiring Stent Implantation
The primary endpoint rate of ARC-defined definite or probable stent thrombosis at 3 years.
Time frame: 3 years
Population: Of the one thousand and eighteen (1018) ITT patients, a total of nine hundred and forty seven (947) patients were included in the primary endpoint analysis. These patients had at least 1050 days of follow-up or had experienced stent thrombosis prior to 1080 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endeavor® Zotarolimus Eluting Coronary Stent System | To Evaluate Overall Stent Thrombosis Rate of the Endeavor® Zotarolimus Eluting Coronary Stent System in a Patient Population Requiring Stent Implantation | 1.2 percentage of participants |
Secondary
Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions.
Total death and and number of patients with all non-fatal myocardial infarction. Cardiac death and number of patients with all non-fatal myocardial infarction. Total death and number of patients with large non-fatal myocardial infarction. Cardiac death and number of patients with large non-fatal myocardial infarction.
Time frame: 3 years
Population: Main secondary endpoint results for the ITT population are similar to the primary endpoint analysis, a total of nine hundred and forty seven (947) ITT patients had sufficient follow-up or an event to be included in the main secondary endpoint analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Endeavor® Zotarolimus Eluting Coronary Stent System | Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions. | the composite rate of death and/or MI | 11.7 percentage of participants |
| Endeavor® Zotarolimus Eluting Coronary Stent System | Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions. | the composite rate of cardiac death and/or MI | 8.2 percentage of participants |
| Endeavor® Zotarolimus Eluting Coronary Stent System | Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions. | composite rate of death and/or large MI | 7.8 percentage of participants |
| Endeavor® Zotarolimus Eluting Coronary Stent System | Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions. | composite rate of cardiac death and/or large MI | 4.2 percentage of participants |