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

Phase 3

Completed

Conditions: Coronary Artery Disease

Interventions: Device: PROMUS Element Coronary Stent System
Drug: Aspirin
Drug: Thienopyridine

Registration Number: NCT01500434

Lead Sponsor: Boston Scientific Corporation

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 can be longer than 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 The study design is consistent with the draft guidance for industry titled, "Coronary Drug-Eluting Stents - Nonclinical and Clinical Studies" (March 2008).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 Long Lesion study is a sub-trial associated with the PLATINUM Workhorse Randomized Controlled Trial, which is registered under NCT00823212.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 102

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 >24 mm and ≤34 mm in length (by visual estimate) in a native coronary artery ≥2.50 mm to ≤4.25 mm in diameter (by visual estimate). 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 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 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PROMUS Element	PROMUS Element Coronary Stent System	Patients who received the PROMUS™ Element Everolimus-Eluting Coronary Stent
PROMUS Element	Thienopyridine	Patients who received the PROMUS™ Element Everolimus-Eluting Coronary Stent
PROMUS Element	Aspirin	Patients who received the PROMUS™ Element Everolimus-Eluting Coronary Stent

Primary Outcome Measures

Name	Time	Method
Target Lesion Failure (TLF)	12 months	Defined as any ischemia-driven revascularization of the target lesion, myocardial infarction (MI, Q-wave and non-Q-wave) related to the target vessel, or cardiac death related to the target vessel.

Secondary Outcome Measures

Name	Time	Method
Target Lesion Failure (TLF)	6 Months	TLF is defined as any ischemia-driven revascularization of the target lesion, myocardial infarction (MI, Q-wave and non-Q-wave) related to the target vessel, or cardiac death related to the target vessel.
Definite + Probable Stent Thrombosis (ST) Rate Based on Academic Research Consortium (ARC) Definition	31-365 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)
Target Lesion Revascularization (TLR)	12 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.
Clinical Procedural Success	In hospital (average of 1-2 days post index procedure)	Defined as mean lesion diameter stenosis \<30% with visually assessed TIMI 3 flow and without the occurrence of in-hospital MI, TVR, or cardiac death
Target Vessel Failure (TVF)	12 months	TVF is defined as any ischemia-driven revascularization of the target vessel, myocardial infarction (MI, Q-wave and non-Q-wave) related to the target vessel or death related to the target vessel. For the purposes of this protocol, if it cannot be determined with certainty whether the MI or death was related to the target vessel, it will be considered a TVF.
All Cause Death	12 months
Cardiac Death Related to the Target Vessel	12 months	Cardiac death is defined as Death due to any of the following: acute MI; cardiac perforation/pericardial tamponade; arrhythmia or conduction abnormality; cerebrovascular accident (CVA) through hospital discharge or CVA suspected of being related to the procedure; complication of the procedure including bleeding, vascular repair, transfusion reaction, or bypass surgery or any death in which a cardiac cause cannot be excluded
Myocardial Infarction (MI) Related to the Target Vessel	12 months	New Q-waves in ≥2 leads lasting ≥0.04 sec with creatine kinase-myoglobin band (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 1 of the following: ECG changes showing 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)	12 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.
Acute Technical Success	Index Procedure	Defined as successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization; expressed per stent

Trial Locations

Locations (30): Mercy General Hospital
🇺🇸
Sacramento, California, United States
Alvarado Hospital
🇺🇸
San Diego, California, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
MediQuest Research Group Inc. at Munroe Regional Medical Center
🇺🇸
Ocala, Florida, United States
William Beaumont Hospital
🇺🇸
Royal Oak, Michigan, United States
Abbott Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Northern Michigan Hospital
🇺🇸
Petoskey, Michigan, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Moses H. Cone Memorial Hospital/LeBauer Cardiovascular Research Foundation
🇺🇸
Greensboro, North Carolina, United States
Mercy St. Vincent Medical Center
🇺🇸
Toledo, Ohio, United States
Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Wake Medical Center
🇺🇸
Raleigh, North Carolina, United States
Ohio Health Research and Innovation Institute
🇺🇸
Columbus, Ohio, United States
Oklahoma Foundation for Cardiovascular Research
🇺🇸
Oklahoma City, Oklahoma, United States
Providence St. Vincent Medical Center
🇺🇸
Portland, Oregon, United States
Providence Health & Services - Washington
🇺🇸
Spokane, Washington, United States
TexSAn Heart Hospital
🇺🇸
San Antonio, Texas, United States
Clinique Pasteur
🇫🇷
Toulouse, France
North Shore Hospital
🇳🇿
Takapuna, New Zealand
Maine Medical Center
🇺🇸
Portland, Maine, United States
North Mississippi Medical Center
🇺🇸
Tupelo, Mississippi, United States
Jackson-Madison County General Hospital
🇺🇸
Jackson, Tennessee, United States
St. Vincents Public,
🇦🇺
Fitzroy, Victoria, Australia
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Ziekenhuis Oost Limburg
🇧🇪
Genk, Belgium
Shonan Kamakura General Hospital
🇯🇵
Kamakura-shi, Kanagawa-ken, Japan
Sakurabashi Watanabe Hospital
🇯🇵
Osaka-shi, Osaka, Japan
P. Stradins University Hospital
🇱🇻
Riga, Latvia
UZ Gasthuisberg
🇧🇪
Leuven, Belgium
Scripps Clinic
🇺🇸
La Jolla, California, United States