Coronary Artery Disease
Conditions
Keywords
Drug-Eluting Stents
Brief summary
EVOLVE 48 is a prospective, open label, single arm, multi-center trial. The purpose of this study is to assess the FDA requirement for safety and effectiveness of the SYNERGY 48 mm Coronary Stent System for the treatment of subjects with atherosclerotic lesion(s) \> 34 mm and ≤ 44 mm in length (by visual estimate) in native coronary arteries ≥2.5 mm to ≤4.0 mm in diameter (by visual estimate).
Interventions
DEVICESYNERGY 48 mm
A drug eluting coronary stent system
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, open label, single arm, multi-center
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Clinical Inclusion Criteria * Subject must be at least 18 years of age * Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed * Subject is eligible for percutaneous coronary intervention (PCI) and is an acceptable candidate for coronary artery bypass grafting (CABG) * Subject has either: * Symptomatic coronary artery disease with one of the following: stenosis ≥ 70%, abnormal fractional flow reserve (FFR), abnormal stress or imaging stress test, or elevated biomarkers prior to the procedure * OR * Documented silent ischemia based on one of the following: abnormal fractional flow reserve (FFR), abnormal stress or imaging stress test, or elevated biomarkers prior to the procedure * Subject is willing to comply with all protocol-required follow-up evaluation Angiographic Inclusion Criteria (visual estimate) * Target lesion must be located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.5 mm and ≤4.0 mm * Target lesion length must be \>34 mm and ≤44 mm (by visual estimate) * Target lesion must have visually estimated stenosis ≥50% and \<100% with thrombolysis in Myocardial Infarction (TIMI) flow \>1 * Coronary anatomy is likely to allow delivery of a study device to the target lesion * The target lesion must be successfully predilated/pretreated. If a non-target lesion is treated, it should be treated first and should be deemed an angiographic success Note: Angiographic success is a mean lesion diameter stenosis \< 50% (\< 30% for stents) in 2 near-orthogonal projections with TIMI 3 flow, as visually assessed by the physician, without the occurrence of prolonged chest pain or ECG changes consistent with MI. Note: Successful predilatation/pretreatment refers to dilatation with a balloon catheter of appropriate length and diameter, or pretreatment with directional or rotational coronary atherectomy, laser or cutting/scoring balloon with no greater than 50% residual stenosis and no dissection greater than National Heart, Lung, Blood Institute (NHLBI) type C. Clinical
Exclusion criteria
* Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI) * Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmias, or ongoing intractable angina * Subject has received an organ transplant or is on a waiting list for an organ transplant * Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure * Planned PCI (including staged procedures) or CABG after the index procedure * Subject previously treated at any time with intravascular brachytherapy * Subject has a known allergy to contrast (that cannot be adequately premedicated) and/or the trial stent system or protocol-required concomitant medications (e.g., platinum, platinum-chromium alloy, stainless steel, everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors, or aspirin) * Subject has one of the following (as assessed prior to enrollment): * Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 24 months * Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.) * Planned procedure that may cause non-compliance with the protocol or confound data interpretation * Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, coumadin) for indications other than acute coronary syndrome * Subject has a platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3 * Subject has a white blood cell (WBC) count \< 3,000 cells/mm3 * Subject has documented or suspected liver disease, including laboratory evidence of hepatitis * Subject is on dialysis or has baseline serum creatinine level \>2.0 mg/dL (177µmol/L) * Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions * Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months * Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding * Subject has signs or symptoms of active heart failure (i.e., New York Heart Association (NYHA) class IV) at the time of the index procedure * Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint * Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure * Subject with known intention to procreate within 12 months after the index procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure) * Subject is a woman who is pregnant or nursing Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Target Lesion Failure Rate at 12-months | 12-month | The primary endpoint is the 12-month Target Lesion Failure (TLF) rate, defined as any ischemia-driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave and non-Q-wave) related to the target vessel, or cardiac death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target Lesion Revascularization (TLR) Rate at 12 Months | 12 months | The TLR overall rate includes: TLR Percutaneous Coronary Intervention (PCI) and TLR Coronary Artery Bypass Graft (CABG) |
| Target Vessel Revascularization (TVR) Rate at 12 Months. | 12 months | TVR overall includes: TVR PCI and TVR CABG |
| Target Vessel Failure (TVF) Rate at 12 Months | 12 months | Target Vessel Failure is defined as any ischemic-driven revascularization of the target vessel, MI related to the target vessel, or any cardiac death. |
| Cardiac Death Rate | 12 months | Cardiac death is defined as death due to any of the following; acute MI, cardiac perforation/pericardial tamponade, arrhythmia or conduction abnormality, CVA through hospital discharge or CVA suspected of being related to the procedure, death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery and any death in which a cardiac cause cannot be excluded. |
| Non-cardiac Death Rate | 12 months | Non-cardiac death is defined as a death not due to cardiac causes as previously defined. |
| All Death Rate | 12 months | — |
| MI (Q-wave and Non-Q-wave) Rate | 12 months | The MI rate includes: MIs related to the Target Vessel, MIs with unknown relationship to the Target Vessel and MIs not related to the Target Vessel. |
| All Death or MI Rate | 12 months | — |
| All Death/MI/TVR Rate | 12 months | — |
| Stent Thrombosis Rate | 12 months | — |
| Periprocedural Technical Success Rate | Day 1 (periprocedural) | Successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization, and post-procedure diameter stenosis of \<30% in 2 near-orthogonal projections with Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the target lesion, as visually assessed by the physician. |
| Periprocedural Clinical Procedural Success Rate | 12 months | Post-procedure lesion diameter stenosis \<30% in 2 near-orthogonal projections with TIMI 3 flow in the target lesion, as visually assessed by the physician, without the occurrence of in-hospital cardiac death, MI, or TVR. |
| Cardiac Death or MI Rate | 12 months | — |
Countries
Latvia, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
A total of 100 patients have been enrolled in the study from April 12, 2018 until January 17, 2019. The Evolve 48 study is anticipated to be completed (final 2-year follow up) in 2021.
Participants by arm
| Arm | Count |
|---|---|
| SYNERGY 48mm SYNERGY is a device/drug combination product comprised of two regulated components: a device (Coronary Stent System) and a drug product (a formulation of everolimus contained in a bioabsorbable polymer coating). | 100 |
| Total | 100 |
Baseline characteristics
| Characteristic | SYNERGY 48mm |
|---|---|
| Age, Continuous | 64.99 years STANDARD_DEVIATION 10.57 |
| Baseline lesion characteristics as determined by the Angiographic core lab, ITT analysis set Left Anterior Descending (LAD) | 40 Participants |
| Baseline lesion characteristics as determined by the Angiographic core lab, ITT analysis set Left Circumflex Artery (LCx) | 14 Participants |
| Baseline lesion characteristics as determined by the Angiographic core lab, ITT analysis set Left Main Coronary Artery (LMCA) | 0 Participants |
| Baseline lesion characteristics as determined by the Angiographic core lab, ITT analysis set Right Coronary Artery (RCA) | 46 Participants |
| History of bleeding disorder | 4 Participants |
| History of CVA | 0 Participants |
| History of Peripheral Vascular Disease (PVD) | 10 Participants |
| History of renal disease | 10 Participants |
| History of TIA | 4 Participants |
| History of Transient Ischemic Attack (TIA) or Coronary vasospasm (CVA) | 4 Participants |
| Hyperlipidemia requiring medication | 82 Participants |
| Hypertension requiring medication | 76 Participants |
| Medically Treated Diabetes | 27 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants |
| Race/Ethnicity, Customized Black, of African heritage | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 85 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Not disclosed | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Region of Enrollment Latvia | 3 participants |
| Region of Enrollment New Zealand | 19 participants |
| Region of Enrollment United Kingdom | 33 participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 60 Participants |
| Smoking Smoking, current | 14 Participants |
| Smoking Smoking, ever | 51 Participants |
| Smoking Smoking, previous | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 100 |
| other Total, other adverse events | 4 / 100 |
| serious Total, serious adverse events | 31 / 100 |
Outcome results
Primary
Target Lesion Failure Rate at 12-months
The primary endpoint is the 12-month Target Lesion Failure (TLF) rate, defined as any ischemia-driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave and non-Q-wave) related to the target vessel, or cardiac death.
Time frame: 12-month
Population: The per-protocol and ITT populations are the same.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Target Lesion Failure Rate at 12-months | 4 percentage of participants |
Secondary
All Death/MI/TVR Rate
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | All Death/MI/TVR Rate | 7 percentage of participants |
Secondary
All Death or MI Rate
Time frame: 12 months
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | All Death or MI Rate | 6 percentage of participants |
Secondary
All Death Rate
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | All Death Rate | 5 percentage of participants |
Secondary
Cardiac Death or MI Rate
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Cardiac Death or MI Rate | 3 percentage of participants |
Secondary
Cardiac Death Rate
Cardiac death is defined as death due to any of the following; acute MI, cardiac perforation/pericardial tamponade, arrhythmia or conduction abnormality, CVA through hospital discharge or CVA suspected of being related to the procedure, death due to complication of the procedure, including bleeding, vascular repair, transfusion reaction, or bypass surgery and any death in which a cardiac cause cannot be excluded.
Time frame: 12 months
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Cardiac Death Rate | 1 percentage of participants |
Secondary
MI (Q-wave and Non-Q-wave) Rate
The MI rate includes: MIs related to the Target Vessel, MIs with unknown relationship to the Target Vessel and MIs not related to the Target Vessel.
Time frame: 12 months
Population: Intent-to-Treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | MI (Q-wave and Non-Q-wave) Rate | 2 percentage of participants |
Secondary
Non-cardiac Death Rate
Non-cardiac death is defined as a death not due to cardiac causes as previously defined.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Non-cardiac Death Rate | 4 percentage of participants |
Secondary
Periprocedural Clinical Procedural Success Rate
Post-procedure lesion diameter stenosis \<30% in 2 near-orthogonal projections with TIMI 3 flow in the target lesion, as visually assessed by the physician, without the occurrence of in-hospital cardiac death, MI, or TVR.
Time frame: 12 months
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Periprocedural Clinical Procedural Success Rate | 100 percentage of participants |
Secondary
Periprocedural Technical Success Rate
Successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization, and post-procedure diameter stenosis of \<30% in 2 near-orthogonal projections with Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the target lesion, as visually assessed by the physician.
Time frame: Day 1 (periprocedural)
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Periprocedural Technical Success Rate | 100 percentage of participants |
Secondary
Stent Thrombosis Rate
Time frame: 12 months
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Stent Thrombosis Rate | 0 percentage of participants |
Secondary
Target Lesion Revascularization (TLR) Rate at 12 Months
The TLR overall rate includes: TLR Percutaneous Coronary Intervention (PCI) and TLR Coronary Artery Bypass Graft (CABG)
Time frame: 12 months
Population: Intent-to-Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Target Lesion Revascularization (TLR) Rate at 12 Months | 1 percentage of participants |
Secondary
Target Vessel Failure (TVF) Rate at 12 Months
Target Vessel Failure is defined as any ischemic-driven revascularization of the target vessel, MI related to the target vessel, or any cardiac death.
Time frame: 12 months
Population: Intent-to-Treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Target Vessel Failure (TVF) Rate at 12 Months | 4 percentage of participants |
Secondary
Target Vessel Revascularization (TVR) Rate at 12 Months.
TVR overall includes: TVR PCI and TVR CABG
Time frame: 12 months
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SYNERGY 48 mm | Target Vessel Revascularization (TVR) Rate at 12 Months. | 1 percentage of participants |