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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01004406
First received: October 29, 2009
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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. FDA approval for phase II received.


Condition Intervention Phase
Acute Coronary Syndrome
Procedure: Percutaneous coronary intervention
Procedure: Intravascular ultrasound with virtual histology
Drug: Atorvastatin
Device: LDL-apheresis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • % 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 ]

Estimated Enrollment: 30
Study Start Date: April 2014
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Patients undergoing clinically indicated, non-emergent coronary angiography and PCI with IVUS-VH of target coronary artery for ACS.
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 2
Patients undergoing clinically indicated, non-emergent coronary angiography and PCI with IVUS-VH of target coronary artery for ACS.
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.

Detailed Description:

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 study have been included in the revised study protocol:

  1. The first stage will enroll 30 patients with a 2 : 1 randomization favoring LDL-apheresis. The safety data will be submitted to the FDA.
  2. The enrollment of the second stage of the study will be contingent to the recommendations of the FDA.
  Eligibility

Ages Eligible for Study:   31 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 within three 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 (greater or equal to 12 hrs) triglyceride levels (greater or equal to 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 within three months 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01004406

Locations
United States, Illinois
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States, 60141-5000
United States, Oklahoma
Oklahoma City VA Medical Center, Oklahoma City, OK
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
VA North Texas Health Care System, Dallas
Dallas, Texas, United States, 75216
Sponsors and Collaborators
Investigators
Principal Investigator: Subhash Banerjee, MD VA North Texas Health Care System, Dallas
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01004406     History of Changes
Other Study ID Numbers: CLIN-010-09S
Study First Received: October 29, 2009
Last Updated: January 14, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
plaque
LDL
statin
endothelial
apheresis
acute coronary syndrome

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014