The PLATINUM Clinical Trial to Assess the PROMUS Element Stent System for Treatment of De Novo Coronary Artery Lesions

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.

This clinical trial compares outcomes in patients treated with PROMUS Element to those in patients treated with a different everolimus-eluting coronary stent. The lesions are of average length in average-sized vessels ("workhorse"). A companion sub-trial evaluates outcomes in smaller vessels (SV) and another sub-trial evaluates outcomes in longer lesions (LL).

The wide-spread use of 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 The study design is consistent with the draft guidance for industry titled, "Coronary Drug-Eluting Stents - Nonclinical and Clinical Studies" (March 2008).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.

The main study is the PLATINUM Workhorse Randomized Controlled Trial, which is registered under NCT00823212. The clinical protocol includes two companion sub-trials with smaller vessels (PLATINUM SV) and longer lesions (PLATINUM LL) plus a Pharmacokinetics sub-trial (PLATINUM PK). The three sub-trials are registered under separate NCT numbers.

Eligibility Criteria:
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 Exclusion Criteria (visual estimate):

* Target lesion meets any of the following criteria:

  * Aorto-ostial location (ie, lesion located within 5 mm of ostium by visual estimate)
  * Left main location
  * Located within 5 mm of origin of the left anterior descending (LAD) coronary artery or left circumflex (LCX) coronary artery by visual estimate
  * Located within a saphenous vein graft or arterial graft
  * Will be accessed via a saphenous vein graft or arterial graft
  * Involves a side branch \>=2.0 mm in diameter by visual estimate
  * Involves a clinically significant side branch \<2.0 mm in diameter by visual estimate that has a clinically significant stenosis at the ostium
  * TIMI flow 0 (total occlusion) or TIMI flow 1 prior to wire crossing
  * Excessive tortuosity proximal to or within the lesion
  * Extreme angulation proximal to or within the lesion
  * Target lesion and/or target vessel proximal to the target lesion is moderately to severely calcified by visual estimate
  * Restenotic from previous intervention
  * Thrombus, or possible thrombus, present in target vessel
* Non-target lesion to be treated during the index procedure meets any of the following criteria:

  * Located within the target vessel
  * Located within a bypass graft (venous or arterial)
  * Left main location
  * Chronic total occlusion
  * Involves a complex bifurcation (eg, bifurcations requiring treatment with more than 1 stent)
  * Restenotic from previous intervention
* Patient has unprotected left main coronary artery disease (\>50% diameter stenosis)
* Patient has protected left main coronary artery disease and a target lesion in the LAD or LCX
* Patient has an additional clinically significant lesion(s) in target vessel for which an intervention within 12 months after the index procedure is likely to be required
* Patient has 2 target lesions in the same vessel that are separated by less than 15 mm (by visual estimate) Note: Multiple focal stenoses will be considered as a single lesion if they can be completely covered with 1 stent.