Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER), Phase I

NCT01004406 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 1 other identifier: CLIN-010-09S
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief 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 II phases and FDA approval for phase II has been received.

Conditions

Acute Coronary Syndrome

Keywords

plaque; LDL; statin; endothelial; apheresis; acute coronary syndrome

Outcome Measures

Primary Outcomes (1)

• Change in the Total Atheroma Volume of the Target Coronary Artery From Baseline to 12 Weeks Post-PCI as Assessed Via Intravascular Ultrasound With Virtual Histology (IVUS-VH)

  The primary effectiveness outcome measure was the change in the total atheroma volume within a ≥ 20 mm long segment of the target coronary artery from baseline to 12 weeks post-PCI. The measurement was done via IVUS-VH at 2 time points (baseline during index PCI and 12-week follow-up).

  baseline and 12-week follow-up

Secondary Outcomes (3)

• Change in % Necrotic Core (NC) Component of Atheroma From Baseline to 12 Weeks Post-PCI as Assessed Via IVUS-VH

  baseline and 12-week follow-up

• Endothelial Progenitor Cell Colony Forming Units (EPC-CFU) Per Milliliter of Peripheral Blood Across Time

  pre-PCI, post-PCI, 4-week follow-up, and 12-week follow-up

• Major Adverse Cardiovascular Events

  6 months

Study Arms (2)

intensive LDL-lowering therapy (ILLT)

EXPERIMENTAL

Patient of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is randomized to LDL-apheresis and an oral daily dose of 40-80mg of Atorvastatin or equivalent

Device: intensive LDL-lowering therapy; Drug: standard statin monotherapy

standard statin monotherapy (SMT)

ACTIVE COMPARATOR

Patient of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is randomized to an oral daily dose of 40-80mg of Atorvastatin or equivalent without LDL-apheresis

Drug: standard statin monotherapy

Interventions

intensive LDL-lowering therapy DEVICE

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

Also known as: LIPOSORBER LA-15 System

intensive LDL-lowering therapy (ILLT)

standard statin monotherapy DRUG

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.

Also known as: Atorvastatin or other equivalent types of statin

intensive LDL-lowering therapy (ILLT); standard statin monotherapy (SMT)

Eligibility Criteria

• Age: 31 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 IVUS-VH of target coronary artery for ACS
• Successful placement of two large bore IV cannulas in bilateral upper extremities
• Fasting (\>= 12 hours) LDL \>= 100mg/dl while on \<= 80mg Atorvastatin or equivalent dose of other statin, performed at time of admission or 3 months prior to PCI.

You may not qualify if:

• 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 hours) 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) less than 60 ml/min if they are diabetic; persons with eGFR of less than 45 ml/min if they are not diabetic
• ST-elevation myocardial infarction at admission
• Abnormal liver function test (LFT) at time of admission or 3 month 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 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 grafting (CABG); endotracheal intubation; unplanned in-aortic balloon pump; left ventricular assist device (LVAD); covered stent; unplanned temporary pacemaker wire; administration of inotropes; CPR) , or PCI resulting in clinical events (death; stroke; myocardial infarction; stent thrombosis) during or within 24 hours after the index PCI

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, 73104, United States

Location

VA North Texas Health Care System, Dallas

Dallas, Texas, 75216, United States

Location

Related Publications (1)

• Banerjee S, Luo P, Reda DJ, Latif F, Hastings JL, Armstrong EJ, Bagai J, Abu-Fadel M, Baskar A, Kamath P, Lippe D, Wei Y, Scrymgeour A, Gleason TC, Brilakis ES. Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER). Circ Cardiovasc Interv. 2020 Aug;13(8):e008933. doi: 10.1161/CIRCINTERVENTIONS.119.008933. Epub 2020 Aug 14.

  PMID: 32791950 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; Plaque, Amyloid

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

Our study is limited by its relatively small sample size and short follow-up. All study sites were Veterans Affairs medical centers and therefore enrolled a disproportionate number of men, limiting the generalizability of its findings

Results Point of Contact

• Title: Dr. Subhash Banerjee
• Organization: VA North Texas Health Care System, Dallas, TX and University of Texas Southwestern Medical Center

Subhash.Banerjee@va.gov, Subhash.Banerjee@UTSouthwestern.edu

214-857-1608

Study Officials

• Subhash Banerjee, MD

  VA North Texas Health Care System, Dallas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: October 30, 2009
• Study Start: September 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2013
• Last Updated: July 30, 2019
• Results First Posted: July 15, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)