Acute Coronary SyndromePhase 3PREMIERNCT01004406
Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER), Phase I
A Phase 3 study testing intensive LDL-lowering therapy and standard statin monotherapy in people with Acute Coronary Syndrome, run by VA Office of Research and Development at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 31 years and older
- Conditions the study is for
- Acute Coronary Syndrome
- What is being tested?
- intensive LDL-lowering therapy and standard statin monotherapy
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2011to Mar 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 31 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 19Show fewer
- 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
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA North Texas Health Care System, Dallas
Dallas, Texas, 75216
Oklahoma City VA Medical Center, Oklahoma City, OK
Oklahoma City, Oklahoma, 73104
About this study
Official title: 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 cardiovascular (CV) events in ACS patients. This study has II phases and FDA approval for phase II has been received.
Read the 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-VH). 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-VH 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 has been included in the revised study protocol:
- The first stage will enroll 30 patients with a 2:1 randomization favoring LDL-apheresis. the safety data will be submitted to the FDA.
- The enrollment of the second stage of the study will be contingent to the recommendations of the FDA.
- Conditions
- Acute Coronary Syndrome
- Being tested
- intensive LDL-lowering therapy, standard statin monotherapy
- Keywords
- plaque, LDL, statin, endothelial, apheresis, acute coronary syndrome
- Medical subject headings
- Acute Coronary Syndrome, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intensive LDL-lowering therapyDevice
Also called LIPOSORBER LA-15 System
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
standard statin monotherapyDrug
Also called Atorvastatin or other equivalent types of statin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: standard statin monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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
The %NC component of atheroma were obtained via IVUS-VH at 2 time points (baseline during index PCI and 12-week follow-up).
Measured: baseline and 12-week follow-up
Endothelial Progenitor Cell Colony Forming Units (EPC-CFU) Per Milliliter of Peripheral Blood Across Time
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, 4-week follow-up, and 12-week follow-up).
Measured: pre-PCI, post-PCI, 4-week follow-up, and 12-week follow-up
Major Adverse Cardiovascular Events
The number of patients who experienced major adverse cardiovascular endpoints (MACE) including death, myocardial infarction, coronary revascularization, and stroke during the follow-up periods.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2009 (estimated)
- Study startSep 2011
- Primary completionJan 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndromeStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Subhash Banerjee, MD, Principal investigator, VA North Texas Health Care System, Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01004406
- Sponsor's protocol ID
- CLIN-010-09S
- Acronym
- PREMIER
- Status last verified
- Jul 2019
- First submitted
- 29 Oct 2009
- Last updated
- 30 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 32791950
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER)
- ClinicalTrials.gov ID
- NCT01004406
- Acronym / sponsor ID
- PREMIER / CLIN-010-09S
- Conditions
- Acute Coronary Syndrome
- Keywords
- plaque, LDL, statin, endothelial, apheresis, acute coronary syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Sep 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 30 Oct 2009 (estimated)
- Results
- Posted 15 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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-VH). 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-VH 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 has been included in the revised study protocol:
- The first stage will enroll 30 patients with a 2:1 randomization favoring LDL-apheresis. the safety data will be submitted to the FDA.
- The enrollment of the second stage of the study will be contingent to the recommendations of the FDA.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intensive LDL-lowering therapy (ILLT) | Experimental | Device: intensive LDL-lowering therapy, Drug: standard statin monotherapyPatient 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 |
| standard statin monotherapy (SMT) | Active comparator | Drug: standard statin monotherapyPatient 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 |
Who may qualify
- Ages
- 31 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intensive LDL-lowering therapyAlso: LIPOSORBER LA-15 SystemThe 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 | Device | intensive LDL-lowering therapy (ILLT) |
| standard statin monotherapyAlso: Atorvastatin or other equivalent types of statinThe 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. | Drug | intensive LDL-lowering therapy (ILLT), standard statin monotherapy (SMT) |
Primary outcome
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)
Time frame: baseline and 12-week follow-up
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).
3 secondary outcomes
Change in % Necrotic Core (NC) Component of Atheroma From Baseline to 12 Weeks Post-PCI as Assessed Via IVUS-VH
Time frame: baseline and 12-week follow-up
Endothelial Progenitor Cell Colony Forming Units (EPC-CFU) Per Milliliter of Peripheral Blood Across Time
Time frame: pre-PCI, post-PCI, 4-week follow-up, and 12-week follow-up
Major Adverse Cardiovascular Events
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32791950Banerjee 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Subhash Banerjee, MD principal investigator
VA North Texas Health Care System, Dallas
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing intensive LDL-lowering therapy and standard statin monotherapy in people with Acute Coronary Syndrome, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: baseline and 12-week follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01004406, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.