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NCT02347098: PREMIER

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

Completed Phase 3 Results posted Last updated 30 October 2019
What this trial tests

Phase 3 trial testing intensive LDL-lowering therapy in Acute Coronary Artery Syndrome in 270 participants. Completed in 30 September 2019.

Timeline
30 March 2015
Primary endpoint
28 February 2018
30 September 2019

Quick facts

Lead sponsorVA Office of Research and Development
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposeprevention
Enrollment270
Start date30 March 2015
Primary completion28 February 2018
Estimated completion30 September 2019
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

VA Office of Research and Development — full company profile →

Who can join

31 and older, any sex, with Acute Coronary Artery Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in the Total Atheroma Volume From Baseline to 12 Weeks Primary · 12 weeks

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 90-day follow-up).

GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)-7.63± 23.78
Standard Statin Monotherapy (SMT)-3.10± 17.74
Change in % Necrotic Core Component of Atheroma Secondary · 12 weeks

The %NC component of atheroma were obtained via IVUS-VH at 2 time points (baseline during index PCI and 90-day follow-up).

GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)0.44± 6.81
Standard Statin Monotherapy (SMT)0.94± 9.89
Endothelial Progenitor Cell Colony Forming Units/ml of Peripheral Blood Across Time Secondary · 12 weeks

The cell culture assay and quantification of circulating EPC-CFU were performed for patients recruited at the Dallas VA center only. The assay were done at 4 time points (pre-PCI, post-PCI, 30-day follow-up, and 90-day follow-up).

baseline pre-PCI
GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)11.85± 9.24
Standard Statin Monotherapy (SMT)11.99± 11.37
baseline post-PCI
GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)15.30± 10.96
Standard Statin Monotherapy (SMT)17.89± 16.91
30-day
GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)21.60± 14.78
Standard Statin Monotherapy (SMT)20.40± 17.87
90-day
GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)16.32± 13.29
Standard Statin Monotherapy (SMT)15.06± 14.33
Major Adverse CV Events Secondary · 6 months

The number of patients who experienced major adverse cardiovascular endpoints (MACE) including death, myocardial infarction, coronary revascularization, and stroke during the follow-up periods.

GroupValue95% CI
Intensive LDL-lowering Therapy (ILLT)5
Standard Statin Monotherapy (SMT)2

Adverse events — posted to ClinicalTrials.gov

Time frame: AE/SAE/UADE were monitored at the study sites throughout the whole period of the study at each clinic visit and telephone contact, beginning as soon as a study participant signs the Informed Consent and continuing through end-of-study for each participant. Most participants were followed for around 6 months for AE/SAE/UADE.. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Intensive LDL-lowering Therapy (ILLT)
Serious: 28/63 (44%)
Deaths: 2/63
Standard Statin Monotherapy (SMT)
Serious: 28/66 (42%)
Deaths: 0/66

Serious adverse events (14 terms)

ReactionSystemIntensive LDL-lowering The…Standard Statin Monotherap…
Cardiac failure congestiveCardiac disorders
Coronary artery diseaseCardiac disorders
Coronary artery stenosisCardiac disorders
Chest painGeneral disorders
Vascular stent restenosisGeneral disorders
Myocardial infarctionCardiac disorders
Atrial fibrillationCardiac disorders
Coronary artery occlusionCardiac disorders
Angina unstableCardiac disorders
Cerebrovascular accidentNervous system disorders
PneumoniaInfections and infestations
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Other adverse events (17 terms — click to expand)

ReactionSystemIntensive LDL-lowering The…Standard Statin Monotherap…
Chest painGeneral disorders
Procedural hypotensionInjury, poisoning and procedural complications
HypotensionVascular disorders
FlushingVascular disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Procedural nauseaInjury, poisoning and procedural complications
EpistaxisRespiratory, thoracic and mediastinal disorders
VertigoEar and labyrinth disorders
Diabetes mellitus inadequate controlMetabolism and nutrition disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
TachycardiaCardiac disorders
Angina pectorisCardiac disorders
BradycardiaCardiac disorders
Renal cystRenal and urinary disorders
NephropathyRenal and urinary disorders
Acute kidney injuryRenal and urinary disorders

Most-reported serious reactions: Cardiac failure congestive, Coronary artery disease, Coronary artery stenosis, Chest pain, Vascular stent restenosis, Myocardial infarction, Atrial fibrillation, Coronary artery occlusion.

Data from ClinicalTrials.gov NCT02347098 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER).
    Banerjee S, Luo P, Reda DJ, Latif F, et al · · 2020 · cited 9× · PMID 32791950 · DOI 10.1161/circinterventions.119.008933
  2. Analysis of Plaque Characteristics by Virtual Histology-Intravascular Ultrasound in Short-Term Follow-Up Post-Acute Coronary Syndrome and Association With Lipid-Lowering Therapy: Insights From the PREMIER Trial.
    Kole A, Hua F, Wei Y, Carlson K, et al · · 2023 · cited 1× · PMID 37158083 · DOI 10.1161/jaha.122.028873

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