Coronary Artery Disease
Conditions
Keywords
drug-eluting stents, DES, atherosclerotic
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of the PROMUS Element™ Everolimus-Eluting Coronary Stent System for the treatment of patients with up to 2 de novo atherosclerotic coronary artery lesions. The lesions are located in vessels that are average-sized.
Detailed description
The wide-spread use of drug-eluting stents (DES) has evolved as standard of care in de novo lesions. The proposed study will evaluate the safety and effectiveness of PROMUS Element for the treatment of de novo atherosclerotic lesions in native coronary arteries. The study design is consistent with the draft guidance for industry titled, Coronary Drug-Eluting Stents - Nonclinical and Clinical Studies (March 2008). During the trial, thienopyridines must be administered according to the 2007 American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions (SCAI) guidelines, which recommended that clopidogrel (75 mg daily) or ticlopidine (250 mg twice daily) be prescribed after stent implantation for at least 6 months in all patients, and for at least 12 months in patients who are not at high risk of bleeding. For sites in the United States, the use of prasugrel is not allowed as part of the PLATINUM Clinical Trial. For sites in other countries, prasugrel may be prescribed according to its approved dosing in countries in which it is available. For patients taking aspirin daily a loading dose is recommended; for patients who have not been taking aspirin daily, aspirin must be administered as a loading dose. Patients continue to take aspirin indefinitely to reduce the risk of thrombosis. This PLATINUM Pharmacokinetics (PK) study is a sub-trial associated with the PLATINUM Workhorse Randomized Controlled Trial, which is registered under NCT00823212. PLATINUM PK was designed to evaluate the elution of everolimus from the PROMUS Element everolimus-eluting stent.
Interventions
DEVICEPROMUS Element Everolimus-Eluting Coronary Stent System
PROMUS Element is a device/drug combination product composed of two components, a device (coronary stent system including a platinum chromium stent platform) and a drug product (a formulation of everolimus contained in a polymer coating).
DRUGAspirin
Patients are required to take aspirin indefinitely after stent implant. It is recommended that aspirin 162-325 mg daily be given for at least 6 months after stent placement and that aspirin 75-162 mg daily be given indefinitely thereafter.
DRUGThienopyridine
Patients must be treated with one of the following thienopyridines for at least 6 months following the index procedure: clopidogrel 75 mg daily; or ticlopidine 250 mg twice daily; or prasugrel (outside the United States and if approved at the time of the procedure). If used, the prescribed dose should be in accordance with approved country-specific labeling. In patients not at high risk of bleeding, thienopyridine treatment should continue for at least 12 months after stent implant.
Sponsors
Boston Scientific Corporation
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
* Patient must be at least 18 years of age * Patient (or legal guardian) understands study requirements and treatment procedures and provides written informed consent before any study-specific tests or procedures are performed * For patients less than 20 years of age enrolled at a Japanese site, patient and patient's legal representative must provide written informed consent before any study-specific tests or procedures are performed * Patient is eligible for percutaneous coronary intervention (PCI) * Patient has documented stable angina pectoris or documented silent ischemia; or unstable angina pectoris * Patient is an acceptable candidate for coronary artery bypass grafting (CABG) * Patient has a left ventricular ejection fraction (LVEF) \>=30% as measured within 30 days prior to enrollment * Patient is willing to comply with all protocol-required follow-up evaluations Angiographic Inclusion Criteria (visual estimate): • Target lesion must be a de novo lesion located in a native coronary artery with a visually estimated reference vessel diameter (RVD) \>=2.50 mm and \<=4.25 mm. Target lesion length must measure (by visual estimate) \<=24 mm. Target lesion must be in a major coronary artery or branch with visually estimated stenosis \>=50% and \<100% with Thrombolysis in Myocardial Infarction (TIMI) flow \>1.
Exclusion criteria
* Patient has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute myocardial infarction (MI) * Patient has had a known diagnosis of recent MI (ie, within 72 hours prior to index procedure) and has elevated enzymes at time of index procedure as follows. * Patients are excluded if any of the following criteria are met at time of the index procedure. * If creatine kinase-myoglobin band(CK-MB) \>2× upper limit of normal (ULN), the patient is excluded regardless of CK Total. * If CK-MB is 1-2× ULN, the patient is excluded if the CK Total is \>2× ULN. * If CK Total/CK MB are not used and Troponin is, patients are excluded if the following criterion is met at time of index procedure. * Troponin \>1× ULN with at least one of the following. * Patient has ischemic symptoms and ECG changes indicative of ongoing ischemia (eg, \>1 mm ST segment elevation or depression in consecutive leads or new left bundle branch block \[LBBB\]); * Development of pathological Q waves in the ECG; or * Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Note: For patients with unstable angina or patients who have had a recent MI, CK Total/CK MB (or Troponin if CK Total/CK MB are not used) must be documented prior to enrolling/randomizing the patient. * Patient has received an organ transplant or is on a waiting list for an organ transplant * Patient is receiving or scheduled to receive chemotherapy within 30 days before or after index procedure * Patient is receiving oral or intravenous immunosuppressive therapy (ie, inhaled steroids are not excluded) or has known life-limiting immunosuppressive or autoimmune disease (eg, human immunodeficiency virus, systemic lupus erythematosus, but not including diabetes mellitus) * Patient is receiving chronic (\>=72 hours) anticoagulation therapy (eg, heparin, coumadin) for indications other than acute coronary syndrome * Patient has platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3 * Patient has white blood cell (WBC) count \<3,000 cells/mm3 * Patient has documented or suspected liver disease, including laboratory evidence of hepatitis * Patient is on dialysis or has known renal insufficiency (ie, estimated creatinine clearance \<50 ml/min by the Cockcroft Gault formula, or \[(140-age)\*lean body weight (in kg)\]/\[plasma creatinine (mg/dl)\*72\]) * Patient has history of bleeding diathesis or coagulopathy or will refuse blood transfusions * Patient has had a cerebrovascular accident (CVA) or transient ischemic attack (TIA) within past 6 months, or has any permanent neurologic defect that may cause non-compliance with the protocol * Target vessel(s) or side branch has been treated with any type of PCI (eg, balloon angioplasty, stent, cutting balloon, atherectomy) within 12 months prior to index procedure * Target vessel(s) has been treated within 10 mm proximal or distal to target lesion (by visual estimate) with any type of PCI (eg, balloon angioplasty, stent, cutting balloon, atherectomy) at any time prior to index procedure * Non-target vessel or side branch has been treated with any type of PCI (eg, balloon angioplasty, stent, cutting balloon, atherectomy) within 24 hours prior to index procedure * Planned or actual target vessel(s) treatment with an unapproved device, directional or rotational coronary atherectomy, laser, cutting balloon, or transluminal extraction catheter immediately prior to stent placement * Planned PCI or CABG after index procedure * Patient previously treated at any time with coronary intravascular brachytherapy * Patient has a known allergy to the study stent system or protocol-required concomitant medications (eg, stainless steel, platinum, cobalt, chromium, nickel, tungsten, acrylic, fluoropolymers, everolimus, thienopyridines, aspirin, contrast) that cannot be adequately premedicated * Patient has active peptic ulcer or active gastrointestinal (GI) bleeding * Patient has one of the following. * Other serious medical illness (eg, cancer, congestive heart failure) that may reduce life expectancy to less than 24 months * Current problems with substance abuse (eg, alcohol, cocaine, heroin, etc.) * Planned procedure that may cause non-compliance with protocol or confound data interpretation * Patient is participating in another investigational drug or device clinical trial that has not reached its primary endpoint * Patient intends to participate in another investigational drug or device clinical trial within 12 months after index procedure * Patient with known intention to procreate within 12 months after 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.) * Patient is a woman who is pregnant or nursing (A pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential) * Patient has more than 2 target lesions, or more than 1 target lesion and 1 non-target lesion, which will be treated during the index procedure Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Everolimus Blood Concentration (Cmax) | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve (AUC 0-24), Everolimus | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent |
| Area Under the Concentration Versus Time Curve (AUC 0-infinity) Everolimus | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after implantation of the last study stent. |
| Time of Occurrence of Maximum Everolimus Concentration (Tmax) | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent |
| Terminal Phase Half-life (t1/2) Everolimus | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent. |
| Total Blood Clearance - Everolimus (CL) | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent. |
| Area Under the Concentration Versus Time Curve (AUC 0-t) Everolimus | Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours | Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent; t is the last time at which concentration can be quantified |
| Myocardial Infarction (MI) Related to the Target Vessel | 6 months | New Q-waves in ≥2 leads lasting ≥0.04 sec with creatine kinase (CK) MB or troponin \>normal; if no new Q-waves total CK levels \>3× normal (peri-percutaneous coronary intervention \[PCI\]) or \>2× normal (spontaneous) with elevated CK-MB or troponin \>3× normal (peri-PCI) or \>2× normal (spontaneous) plus at least one of the following: ECG changes indicating new ischemia (new ST-T changes, left bundle branch block), imaging evidence of new loss of viable myocardium, or new regional wall motion abnormality. Similar for MI diagnosis post coronary artery bypass graft with CK-MB or troponin \>5× normal |
| Target Vessel Revascularization (TVR) | 6 months | TVR is any ischemia-driven repeat percutaneous intervention to improve blood flow, or bypass surgery of not previously existing lesions with diameter stenosis ≥50% by quantitative coronary angiography in the target vessel, including the target lesion. |
| Target Lesion Revascularization (TLR) | 6 months | TLR is any ischemia-driven repeat percutaneous intervention to improve blood flow of the successfully treated target lesion or bypass surgery of the target vessel with a graft distally to the successfully treated target lesion. |
| Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition | 24 hours | DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: \>24 hours to 30 days post; late ST: \>30 days to 1 year post; Very late ST: \>1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days). |
| Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition | >24 hours-30 days | DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: \>24 hours to 30 days post; late ST: \>30 days to 1 year post; Very late ST: \>1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days). |
| All Death | 6 months | Number of participants no longer alive |
Countries
Japan, United States
Participant flow
Recruitment details
From October 9, 2009 to February 9, 2010 there were 11 patients enrolled at 2 investigative sites in the United States and 11 patients enrolled at 3 sites in Japan. All enrolled patients received a PROMUS Element study stent.
Participants by arm
| Arm | Count |
|---|---|
| PROMUS Element Patients who received the PROMUS Element everolimus-eluting stent (EES) implanted using standard percutaneous coronary intervention (PCI) technique | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | PROMUS Element |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 9.5 |
| Body Mass Index | 26.52 kg/m^2 STANDARD_DEVIATION 4.79 |
| Cardiac History History of Multivessel Disease | 9 Participants |
| Cardiac History Previous Coronary Artery Bypass Graft (CABG) | 2 Participants |
| Cardiac History Previous Myocardial Infarction (MI) | 4 Participants |
| Cardiac History Previous Percutaneous Coronary Intervention (PCI) | 9 Participants |
| Cardiac History Silent Ischemia | 5 Participants |
| Cardiac History Stable Angina | 15 Participants |
| Cardiac History Unstable Angina | 2 Participants |
| Cardiac History - Left Ventricular Ejection Fraction | 59.64 Percent (of blood emptied) STANDARD_DEVIATION 10.09 |
| Cardiac Risk Factors Hyperlipidemia Requiring Medication | 16 Participants |
| Cardiac Risk Factors Hypertension Requiring Medication | 18 Participants |
| Cardiac Risk Factors Medically Treated Diabetes | 5 Participants |
| Cardiac Risk Factors Smoking, ever | 14 Participants |
| Comorbidities History of Cerebrovascular Accident | 3 Participants |
| Comorbidities History of Peripheral Vascular Disease | 2 Participants |
| Comorbidities History of Renal Disease | 0 Participants |
| Comorbidities History of Transient Ischemic Attack | 2 Participants |
| Height | 165.57 Centimeters STANDARD_DEVIATION 12.55 |
| Lesion Characteristic: Lesion Location Distal | 2 Participants |
| Lesion Characteristic: Lesion Location Mid | 13 Participants |
| Lesion Characteristic: Lesion Location Proximal | 9 Participants |
| Lesion Characteristic-Percent Diameter Stenosis | 73.15 Percent STANDARD_DEVIATION 11.24 |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 0 | 0 Lesions |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 1 | 0 Lesions |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 2 | 0 Lesions |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 3 | 24 Lesions |
| Lesion Characteristics Bend >45 Degrees | 13 Lesions |
| Lesion Characteristics Bend >90 Degrees | 2 Lesions |
| Lesion Characteristics Bifurcation | 1 Lesions |
| Lesion Characteristics Calcification, any | 4 Lesions |
| Lesion Characteristics Eccentric Lesion | 13 Lesions |
| Lesion Characteristics Tortuosity, any | 1 Lesions |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class A | 1 Lesions |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class B1 | 4 Lesions |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class B2 | 15 Lesions |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class C | 4 Lesions |
| Lesion Characteristics: Reference Vessel Diameter, Minimum Lumen Diameter, Length Lesion Length | 12.11 millimeters STANDARD_DEVIATION 4.69 |
| Lesion Characteristics: Reference Vessel Diameter, Minimum Lumen Diameter, Length Minimum Lumen Diameter | 0.73 millimeters STANDARD_DEVIATION 0.38 |
| Lesion Characteristics: Reference Vessel Diameter, Minimum Lumen Diameter, Length Reference Vessel Diameter | 2.64 millimeters STANDARD_DEVIATION 0.46 |
| Lesion Characteristic: Target Lesion Vessel Left Anterior Descending Artery | 4 Lesions |
| Lesion Characteristic: Target Lesion Vessel Left Circumflex Artery | 7 Lesions |
| Lesion Characteristic: Target Lesion Vessel Right Coronary Artery | 13 Lesions |
| Region of Enrollment Japan | 11 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 18 Participants |
| Weight | 73.68 Kilograms STANDARD_DEVIATION 19.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 22 |
| serious Total, serious adverse events | 2 / 22 |
Outcome results
Primary
Maximum Observed Everolimus Blood Concentration (Cmax)
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: The analysis groups reported here had 3 or more subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Maximum Observed Everolimus Blood Concentration (Cmax) | 0.71 ng/mL | Standard Deviation 0.09 |
| Everolimus Dose of 102.4 µg | Maximum Observed Everolimus Blood Concentration (Cmax) | 0.67 ng/mL | Standard Deviation 0.15 |
| Everolimus Dose of 138.6 µg | Maximum Observed Everolimus Blood Concentration (Cmax) | 0.91 ng/mL | Standard Deviation 0.2 |
Secondary
All Death
Number of participants no longer alive
Time frame: 6 months
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | All Death | 0.0 percentage of participants who died |
Secondary
Area Under the Concentration Versus Time Curve (AUC 0-24), Everolimus
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: The analysis groups reported here had 3 or more subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-24), Everolimus | 6.83 ng*hr/mL | Standard Deviation 2.03 |
| Everolimus Dose of 102.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-24), Everolimus | 6.14 ng*hr/mL | Standard Deviation 1.1 |
| Everolimus Dose of 138.6 µg | Area Under the Concentration Versus Time Curve (AUC 0-24), Everolimus | 9.51 ng*hr/mL | Standard Deviation 0.64 |
Secondary
Area Under the Concentration Versus Time Curve (AUC 0-infinity) Everolimus
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after implantation of the last study stent.
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: Analysis groups have ≥3 subjects. Everolimus concentrations declined rapidly in all subjects; AUC0-∞ could be inaccurately determined for a subset of samples. AUC0-∞ determined by extrapolation of terminal phase. Concentrations not above detection limit in the terminal phase for enough time points for most subjects to accurately determine AUC0-∞.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-infinity) Everolimus | 19.26 ng*hr/mL | Standard Deviation 11.69 |
| Everolimus Dose of 102.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-infinity) Everolimus | 12.95 ng*hr/mL | Standard Deviation 2.05 |
| Everolimus Dose of 138.6 µg | Area Under the Concentration Versus Time Curve (AUC 0-infinity) Everolimus | 60.74 ng*hr/mL | Standard Deviation 25.95 |
Secondary
Area Under the Concentration Versus Time Curve (AUC 0-t) Everolimus
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent; t is the last time at which concentration can be quantified
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: The analysis groups reported here had 3 or more subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-t) Everolimus | 7.27 ng*hr/mL | Standard Deviation 4.97 |
| Everolimus Dose of 102.4 µg | Area Under the Concentration Versus Time Curve (AUC 0-t) Everolimus | 6.45 ng*hr/mL | Standard Deviation 5.26 |
| Everolimus Dose of 138.6 µg | Area Under the Concentration Versus Time Curve (AUC 0-t) Everolimus | 10.87 ng*hr/mL | Standard Deviation 7.36 |
Secondary
Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition
DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: \>24 hours to 30 days post; late ST: \>30 days to 1 year post; Very late ST: \>1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days).
Time frame: >30 days-1 year
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition | 0.0 percentage of participants |
Secondary
Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition
DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: \>24 hours to 30 days post; late ST: \>30 days to 1 year post; Very late ST: \>1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days).
Time frame: >24 hours-30 days
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Definite + Probable Stent Thrombosis Rate Based on Academic Research Consortium (ARC) Definition | 0.0 percentage of participants |
Secondary
Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition
DEFINITE ST: acute coronary syndrome and angiographic or pathologic evidence of stent thrombosis; PROBABLE ST: unexplained death within 30 days or target-vessel infarction without angiographic information ARC ST is reported as a cumulative value at different time points and within the different separate time points. Time 0 is the time point after the guide catheter has been removed. Acute ST: 0-24 hours after stent implantation; Subacute ST: \>24 hours to 30 days post; late ST: \>30 days to 1 year post; Very late ST: \>1 year post; NOTE: Acute/subacute can be replaced by early ST (0-30 days).
Time frame: 24 hours
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition | 0.0 percentage of participants |
Secondary
Myocardial Infarction (MI) Related to the Target Vessel
New Q-waves in ≥2 leads lasting ≥0.04 sec with creatine kinase (CK) MB or troponin \>normal; if no new Q-waves total CK levels \>3× normal (peri-percutaneous coronary intervention \[PCI\]) or \>2× normal (spontaneous) with elevated CK-MB or troponin \>3× normal (peri-PCI) or \>2× normal (spontaneous) plus at least one of the following: ECG changes indicating new ischemia (new ST-T changes, left bundle branch block), imaging evidence of new loss of viable myocardium, or new regional wall motion abnormality. Similar for MI diagnosis post coronary artery bypass graft with CK-MB or troponin \>5× normal
Time frame: 6 months
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Myocardial Infarction (MI) Related to the Target Vessel | 0.0 percentage of participants |
Secondary
Target Lesion Revascularization (TLR)
TLR is any ischemia-driven repeat percutaneous intervention to improve blood flow of the successfully treated target lesion or bypass surgery of the target vessel with a graft distally to the successfully treated target lesion.
Time frame: 6 months
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Target Lesion Revascularization (TLR) | 0.0 percentage of participants |
Secondary
Target Vessel Revascularization (TVR)
TVR is any ischemia-driven repeat percutaneous intervention to improve blood flow, or bypass surgery of not previously existing lesions with diameter stenosis ≥50% by quantitative coronary angiography in the target vessel, including the target lesion.
Time frame: 6 months
Population: Analysis was intention to treat; all patients in the study underwent clinical follow up to provide the information needed for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus Dose of 95.4 µg | Target Vessel Revascularization (TVR) | 0.0 percentage of participants |
Secondary
Terminal Phase Half-life (t1/2) Everolimus
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent.
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: Analysis groups have ≥3 subjects. Everolimus concentrations declined rapidly in all subjects; half-life could be inaccurately determined for a subset of samples; determined by extrapolation of terminal phase. Concentrations not above detection limit in the terminal phase for enough time points for most subjects to accurately determine half-life.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Terminal Phase Half-life (t1/2) Everolimus | 34.19 Hours | Standard Deviation 20.81 |
| Everolimus Dose of 102.4 µg | Terminal Phase Half-life (t1/2) Everolimus | 22.83 Hours | Standard Deviation 7.2 |
| Everolimus Dose of 138.6 µg | Terminal Phase Half-life (t1/2) Everolimus | 136.06 Hours | Standard Deviation 62.08 |
Secondary
Time of Occurrence of Maximum Everolimus Concentration (Tmax)
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point) and at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: Analysis groups reported here had 3 or more subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Time of Occurrence of Maximum Everolimus Concentration (Tmax) | 0.47 hours | Standard Deviation 0.03 |
| Everolimus Dose of 102.4 µg | Time of Occurrence of Maximum Everolimus Concentration (Tmax) | 0.62 hours | Standard Deviation 0.23 |
| Everolimus Dose of 138.6 µg | Time of Occurrence of Maximum Everolimus Concentration (Tmax) | 0.52 hours | Standard Deviation 0.09 |
Secondary
Total Blood Clearance - Everolimus (CL)
Venous blood draw up to 24 hours prior to implantation of the first study stent (predose time point), 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours after completion of implantation of the last study stent.
Time frame: Predose <24 hours; post dose at 30 minutes, 1, 2, 4, 6, 12, 24, 48, and 72 hours
Population: Analysis groups have ≥3 subjects. Everolimus concentrations declined rapidly in all subjects; CL could be inaccurately determined for a subset of samples; determined by extrapolation of terminal phase. Concentrations not above detection limit in the terminal phase for enough time points for most subjects to accurately determine CL value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus Dose of 95.4 µg | Total Blood Clearance - Everolimus (CL) | 6445 L/h | Standard Deviation 3924 |
| Everolimus Dose of 102.4 µg | Total Blood Clearance - Everolimus (CL) | 8044 L/h | Standard Deviation 1276 |
| Everolimus Dose of 138.6 µg | Total Blood Clearance - Everolimus (CL) | 2511 L/h | Standard Deviation 1073 |