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Intensive Lipid-Lowering Therapy for Patients With Acute Coronary Syndrome (PREMIER)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01004406
First received: October 29, 2009
Last updated: August 28, 2014
Last verified: August 2014

October 29, 2009
August 28, 2014
September 2011
January 2013   (final data collection date for primary outcome measure)
Change in the total atheroma volume within at least 20mm of the target coronary artery from baseline to 12 weeks post-PCI. The measurement will be done via IVUS-VH. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01004406 on ClinicalTrials.gov Archive Site
  • % necrotic core component of atheroma [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Endothelial progenitor cell colony forming units/ml of peripheral blood [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Major adverse CV events during the follow-up periods [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Intensive Lipid-Lowering Therapy for Patients With Acute Coronary Syndrome
Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER)

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 CV events in ACS patients. This study has II phases and FDA approval for phase II has been received.

Using statins to lower blood cholesterol, and specifically LDL, is well established as a long-term strategy to reduce CVs and even death. But the most intensive pharmacologic lipid-lowering therapy with statins, though proven superior to standard dose regimens, is still associated with an unacceptably high rate of recurrent CV events early after an ACS. This study hypothesizes that for ACS patients undergoing percutaneous coronary intervention (PCI), intensive lipid-lowering therapy consisting of statins and LDL-apheresis (ILLT) will significantly reduce the total coronary atheroma volume of vulnerable plaque and augment mobilization of peripherally circulating EPC colony forming units, compared to guideline statin monotherapy (SMT). ILLT will lead to fewer CV events for these patients.

Patients presenting at two VA sites with ACS will be screened and consented before undergoing uncomplicated PCI (balloons or stents) and intravascular ultrasound with virtual histology (IVUS-HS). They will then be randomized into the ILLT arm or SMT arm of the study. The ILLT group will receive one treatment of LDL-apheresis plus a daily oral 80mg dose of Atorvastatin; the SMT group will only get the Atorvastatin. Patients will again undergo IVUS-HS 12 weeks after enrollment to measure atheroma volume; EPC level will also be checked.

The four-year duration of the study includes 24 months of accrual, six months of follow-up, and 12 months of study closure and data analysis. A two-sample t-test of mean difference with 90% power and 0.65 Cohen's D effect size provides a total sample size estimate of 102. Counting 20% drop-out rate, the sample size increases to 128.

The recent FDA recommendations regarding the design of the studyhas been included in the revised study protocol:

  1. The first stage will enroll 30 patients with a 2:1 radomization favoring LDL-apheresis. the safety data will be submitted to the FDA.
  2. The enrollment of the second stage of the sstudy will be contingent to the recomendations of the FDA.
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Acute Coronary Syndrome
  • Procedure: Percutaneous coronary intervention
    Widening of coronary arteries using balloons or stents.
  • Procedure: Intravascular ultrasound with virtual histology
    IVUS-VH allows for the identification of discrete plaque components using radiofrequency backscatter data. The technology can visualize the coronary artery wall and measure atherosclerosis volume.
  • Drug: Atorvastatin
    80mg daily oral dose of Atorvastatin to lower LDL in blood.
  • Device: LDL-apheresis
    The device proposed for use in this study is the LIPOSORBER LA-15 System, manufactured by Kaneka Pharma America LLC. The Liposorber separates plasma from whole blood, then removes LDL from the plasma, recombines the plasma and blood cells, and returns the blood into the patient's body; the 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.
  • Experimental: Arm 1
    Patients undergoing clinically indicated, non-emergent coronary angiography and PCI with IVUS-VH of target coronary artery for ACS.
    Interventions:
    • Procedure: Percutaneous coronary intervention
    • Procedure: Intravascular ultrasound with virtual histology
    • Drug: Atorvastatin
    • Device: LDL-apheresis
  • Experimental: Arm 2
    Patients undergoing clinically indicated, non-emergent coronary angiography and PCI with IVUS-VH of target coronary artery for ACS.
    Interventions:
    • Procedure: Percutaneous coronary intervention
    • Procedure: Intravascular ultrasound with virtual histology
    • Drug: Atorvastatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
128
March 2014
January 2013   (final data collection date for primary outcome measure)

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 IVUS-VH of target coronary artery for ACS
  • Successful placement of two large bore IV cannulas in bilateral upper extremities
  • Fasting ( 12 hrs) LDL 100mg/dl while on 80mg Atorvastatin or equivalent dose of other statin, performed at time of admission or 3 months 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 GFR 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; 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 CABG; endotracheal intubation; unplanned in-aortic balloon pump; 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
  • 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
Both
31 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01004406
CLIN-010-09S
Yes
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: Subhash Banerjee, MD VA North Texas Health Care System, Dallas
Department of Veterans Affairs
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP