Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER), Phase II
Condition: Acute Coronary Artery Syndrome
MeSH terms: Syndrome
Intervention: intensive LDL-lowering therapy; standard statin monotherapy
Intervention description: The intensive LDL-lowering therapy uses LDL-apheresis in addition to the standard statin therapy. The device used in this study is the LIPOSORBER LA-15 System, manufactured by Kaneka Pharma America LLC. A filter separates plasma from whole blood, the Liposorber -columns remove LDL from the plasma. The system recombines plasma and blood cells and returns them into the patient's body. This procedure typically takes about 3 hours. The procedure provides an immediate reduction in a patient's lipid levels. A single apheresis treatment can lower LDL by more than 80%, but levels return to baseline within 3 weeks.; The standard statin therapy of 40-80mg oral daily dose of Atorvastatin or other equivalent types of statin to lower LDL in blood for both randomized groups.
Intervention MeSH terms: Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 270.0
Sex: All
Minimum age: 31 Years
Healthy volunteers: No
Keywords: plaque; LDL; statin; endothelial; apheresis; acute coronary artery syndrome

Summary:

      The purpose of this randomized, multi-site, clinical trial is to determine whether intensive
      therapy consisting of cholesterol-lowering statin drugs plus apheresis to cleanse the blood
      of low-density lipoprotein (LDL) cholesterol is more effective than statin therapy alone in
      reducing plaque volume in heart arteries of patients who have already suffered an acute
      coronary syndrome (ACS). The study will also investigate whether this intensive approach can
      help increase the presence of endothelial progenitor cells (EPC), stem cells that have been
      shown to reduce cardiovascular (CV) events in ACS patients. This study has two phases and FDA
      approval for phase II has been received and all information has been updated to reflect
      PREMIER Phase II.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide informed consent (including HIPAA)

          -  Age >30 years

          -  Presenting with acute coronary syndrome (ACS), manifested as unstable angina or
             non-ST-elevation myocardial infarction

          -  Referred for clinically-indicated, non-emergent (the procedure is not required to be
             performed within 3 hours after patient presentation) coronary angiography and PCI with
             Intravascular Ultrasound with Virtual Histology (IVUS-VH) of target coronary artery
             for ACS

          -  Successful placement of two large bore IV cannulas in bilateral upper extremities

          -  Fasting (12 hrs.) LDL 70mg/dl while on less than or equal to 80mg Atorvastatin or
             equivalent dose of other statin, performed at time of admission or prior to PCI.

        Exclusion Criteria:

          -  Known allergy to aspirin, clopidogrel, statins, or iodinated contrast

          -  Positive pregnancy test, planning to become pregnant, or breast-feeding

          -  Coexisting conditions that limit life expectancy to less than six months or affect
             patient compliance

          -  Uncontrolled fasting (12 hrs.) triglyceride levels ( 500mg/dl)

          -  Already participating in an investigational device or drug study

          -  History of heparin induced thrombocytopenia (HIT)

          -  Persons with estimated glomerular filtration rate (eGFR) of less than 45 ml/min

          -  ST-elevation myocardial infarction at admission

          -  Abnormal liver function test (LFT) at time of admission or prior to PCI with abnormal
             LFT defined as any liver transaminases (ALT or AST) 3 times the upper limit of the
             normal laboratory reference

          -  Pre-PCI or post-PCI left ventricular ejection fraction <25% by echo or cardiac
             catheterization done after admission

          -  Pre-PCI, intra-PCI, or post-PCI hemodynamic instability with hypotension

          -  Pre-PCI, intra-PCI, or post-PCI cardiac arrest

          -  Pre-PCI or post-PCI acute heart failure with or without pulmonary edema

          -  Intra-PCI or post-PCI sustained ventricular tachycardia

          -  Complicated PCI, defined as PCI with any of the vascular access complications (large
             hematoma with lump > 5 cm or requiring medical treatment; arteriovenous (AV) fistula;
             pseudo aneurysm requiring treatment; retroperitoneal bleeding), or PCI with any of the
             procedural complications (abrupt vessel closure; no-reflow phenomenon; new
             angiographic thrombus; new major dissection with reduced flow; catheter-related
             thrombus), or PCI requiring further medical treatments (urgent coronary artery bypass
             graft (CABG); endotracheal intubation; unplanned in-aortic balloon pump; left
             ventricular assist device (LVAD); covered stent; unplanned temporary pacemaker wire;
             administration of inotropes; cardiopulmonary resuscitation (CPR)) , or PCI resulting
             in clinical events (death; stroke; myocardial infarction; stent thrombosis) during or
             within 24 hours after the index PCI

          -  Post-PCI ongoing chest pain

          -  Post-PCI severe groin pain and hematoma > 5cm in diameter

          -  Persons whose hemoglobin is less than 9 grams following the index PCI/IVUS procedure,
             or who experience a drop in hemoglobin of greater than or equal to 2 grams following
             the procedure

          -  Not able to comply with study protocol as determined by the investigators