Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vascular Effects of Alirocumab in Acute MI-Patients (PACMAN-AMI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03067844
Recruitment Status : Completed
First Posted : March 1, 2017
Last Update Posted : February 24, 2022
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE February 24, 2017
First Posted Date  ICMJE March 1, 2017
Last Update Posted Date February 24, 2022
Actual Study Start Date  ICMJE April 25, 2017
Actual Primary Completion Date October 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
Change in percent atheroma volume (PAV) [ Time Frame: Baseline to week 52 ]
Change in PAV by greyscale intravascular ultrasound (IVUS)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2019)
  • Change in total lipid-core burden index (LCBItotal) [ Time Frame: Baseline to week 52 ]
    Change in LCBItotal as determined by near infrared spectroscopy (NIRS)
  • Change in maximum LCBI in any 4-mm segment (Powered) [ Time Frame: Baseline to week 52 ]
    Change in maximum LCBI in any 4-mm segment (maxLCBI4mm) as determined by NIRS
  • Change in minimal fibrous cap thickness (Powered) [ Time Frame: Baseline to week 52 ]
    Change in minimal fibrous cap thickness as determined by optical coherence tomography (OCT)
  • Change in mean fibrous cap thickness [ Time Frame: Baseline to week 52 ]
    Change in mean fibrous cap thickness as determined by OCT
  • Change in average angular extension (AAE) of macrophages [ Time Frame: Baseline to week 52 ]
    Change in AAE of macrophages as determined by OCT
  • Change in normalized total atheroma volume (NTAV) [ Time Frame: Baseline to week 52 ]
    Change in NTAV by IVUS
  • Change in LDL-cholesterol [ Time Frame: Baseline to week 52 ]
    Change in LDL-cholesterol
  • Change in hsCRP [ Time Frame: Baseline to week 52 ]
    Change in hsCRP
  • Change in high sensitivity troponin T (hsTnT) [ Time Frame: Baseline to week 52 ]
    Change in hsTnT
  • Change in N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) [ Time Frame: Baseline to week 52 ]
    Change in NT-pro-BNP
  • Change in further biomarkers [ Time Frame: Baseline to week 52 ]
    Change in lipid and inflammatory markers and their association with indices of plaque progression/regression
  • Death [ Time Frame: Baseline to week 52 ]
    Any death, cardiac death
  • Non-fatal myocardial infarction [ Time Frame: Baseline to week 52 ]
    Any non-fatal myocardial infarction
  • Ischemia-driven coronary revascularization [ Time Frame: Baseline to week 52 ]
    Any ischemia-driven coronary revascularization
  • Stroke [ Time Frame: Baseline to week 52 ]
    Any ischemic stroke/transient ischemic attack
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Change in total lipid-core burden index (LCBItotal) [ Time Frame: Baseline to week 52 ]
    Change in LCBItotal as determined by near infrared spectroscopy (NIRS)
  • Change in maximum LCBI in any 4-mm segment [ Time Frame: Baseline to week 52 ]
    Change in maximum LCBI in any 4-mm segment (maxLCBI4mm) as determined by NIRS
  • Change in minimal fibrous cap thickness [ Time Frame: Baseline to week 52 ]
    Change in minimal fibrous cap thickness as determined by optical coherence tomography (OCT)
  • Change in mean fibrous cap thickness [ Time Frame: Baseline to week 52 ]
    Change in mean fibrous cap thickness as determined by OCT
  • Change in average angular extension (AAE) of macrophages [ Time Frame: Baseline to week 52 ]
    Change in AAE of macrophages as determined by OCT
  • Change in normalized total atheroma volume (NTAV) [ Time Frame: Baseline to week 52 ]
    Change in NTAV by IVUS
  • Change in LDL-cholesterol [ Time Frame: Baseline to week 52 ]
    Change in LDL-cholesterol
  • Change in hsCRP [ Time Frame: Baseline to week 52 ]
    Change in hsCRP
  • Change in high sensitivity troponin T (hsTnT) [ Time Frame: Baseline to week 52 ]
    Change in hsTnT
  • Change in N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) [ Time Frame: Baseline to week 52 ]
    Change in NT-pro-BNP
  • Change in further biomarkers [ Time Frame: Baseline to week 52 ]
    Change in lipid and inflammatory markers and their association with indices of plaque progression/regression
  • Death [ Time Frame: Baseline to week 52 ]
    Any death, cardiac death
  • Non-fatal myocardial infarction [ Time Frame: Baseline to week 52 ]
    Any non-fatal myocardial infarction
  • Ischemia-driven coronary revascularization [ Time Frame: Baseline to week 52 ]
    Any ischemia-driven coronary revascularization
  • Stroke [ Time Frame: Baseline to week 52 ]
    Any ischemic stroke/transient ischemic attack
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vascular Effects of Alirocumab in Acute MI-Patients
Official Title  ICMJE Effects of the PCSK9 Antibody AliroCuMab on Coronary Atherosclerosis in PatieNts With Acute Myocardial Infarction: A Serial, Multivessel, Intravascular Ultrasound, Near-Infrared Spectroscopy And Optical Coherence Tomography Imaging Study
Brief Summary

Coronary artery disease (CAD) is the most frequent cause of mortality in the industrialized world. Hypercholesterolemia is a major risk factor for the development and progression of CAD. While statins currently represent the first-line, gold-standard therapy for primary and secondary prevention of cardiovascular morbidity and mortality, nearly 50% of patients in Europe and Canada treated with statins do not achieve their target levels of low-density lipoprotein cholesterol (LDL-C) or cannot tolerate effective statin doses.

Recently, a growing number of studies of PCSK9 inhibitors in a wide spectrum of patients with hyperlipidemia on or off lipid-lowering therapy, familial hypercholesterolemia, and statin intolerance demonstrated consistent, profound, and sustained reductions in LDL-C with greater magnitude of reduction as compared with high-dose statin regimens. However, the effects of PCSK9 inhibition on coronary plaque morphology remain unknown.

This study will investigate the effect of the PCSK9 inhibitor alirocumab in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) in the infarct-related artery and receiving guideline-recommended high-intensity statin therapy. A serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study will be performed to determine the change in plaque volume at week 52. A total of 294 patients will be enrolled in the study and randomized in a 1:1 ratio to either alirocumab or placebo.

Detailed Description

Substudies

  • Biobank/drug monitoring, all sites
  • Lipidomics (n=294), all sites
  • Platelet Function (n=~150), Bern
  • Endothelial Function (n=~150), Bern
  • Neatherosclerosis (n=~294), all sites
  • Neutrophilic Extracellular Trap (NET), (n=~50), Vienna
  • OCT-NIRS/IVUS Matching Substudy (n=~104), Bern
  • Positron Emission Computed Tomography (PET-CT), (n=~50), Copenhagen
  • Shear Stress (n=~294), London
  • Quantitative Flow Ratio (QFR) (n=~294), Bern
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Vessel
  • Coronary Circulation
  • Atheroma; Myocardial
Intervention  ICMJE Drug: Alirocumab
Pre-filled auto-injector pen every second week, starting at day 1 and up to week 50
Study Arms  ICMJE
  • Experimental: Alirocumab
    Alirocumab 150 mg/mL, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
    Intervention: Drug: Alirocumab
  • Placebo Comparator: Placebo
    Placebo, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
    Intervention: Drug: Alirocumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 30, 2019)
294
Original Estimated Enrollment  ICMJE
 (submitted: February 28, 2017)
220
Actual Study Completion Date  ICMJE October 13, 2021
Actual Primary Completion Date October 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female, age ≥18 years at screening;
  • Acute myocardial infarction: acute ST-segment elevation myocardial infarction (STEMI) with pain onset within ≤24h, or non-ST segment elevation myocardial infarction (NSTEMI), with at least one coronary segment (culprit lesion) requiring PCI;
  • LDL-C ≥70 mg/dL (≥1.8 mmol/L) assessed prior to, or during PCI in patients who have been receiving any stable statin regimen within ≥ 4 weeks prior to enrollment; OR LDL-C ≥125 mg/dL (≥3.2 mmol/L) in patients who are statin-naïve or have not been on stable statin regimen for ≥ 4 weeks prior to enrollment;
  • At least two major native coronary arteries ("target vessels") each meeting the following criteria for intracoronary imaging immediately following the qualifying PCI procedure: Angiographic evidence of <50% reduction in lumen diameter by angiographic visual estimation;
  • Target vessel deemed to be accessible to imaging catheters and suitable for intracoronary imaging in the proximal (50mm) segment ("target segment");
  • Target vessel may not be a bypass (saphenous vein or arterial) graft or a bypassed native vessel;
  • Target vessel must not have undergone previous PCI within the target segment;
  • Target vessel is not candidate for intervention at the time of qualifying PCI or over the following 6 months in the judgment of the Investigator;
  • Hemodynamic stability allowing the repetitive administration of nitroglycerine;
  • Ability to understand the requirements of the study and to provide informed consent;
  • Willingness to undergo follow-up intracoronary imaging.

Exclusion Criteria:

  • Left-main disease, defined as ≥50% reduction in lumen diameter of the left main coronary artery by angiographic visual estimation;
  • Three-vessel disease, defined as ≥70% reduction in lumen diameter of three major epicardial coronary arteries by angiographic visual estimation or in major branches of one or more of these arteries, irrespective of the localization (proximal 50mm or more distal localization) of the obstructive lesions;
  • History of coronary artery bypass surgery;
  • "Thrombolysis In Myocardial Infarction" (TIMI) flow <2 of the infarct-related artery after PCI;
  • Unstable clinical status (hemodynamic or electrical instability);
  • Significant coronary calcification or tortuosity deemed to preclude IVUS, NIRS and OCT evaluation;
  • Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening;
  • Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2;
  • Active liver disease or hepatic dysfunction;
  • Known intolerance to rosuvastatin OR known statin intolerance;
  • Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel;
  • Known sensitivity to any substances to be administered, including known statin intolerance;
  • Patients who previously received alirocumab or other PCSK9 inhibitor;
  • Patient who received cholesterol ester transfer protein inhibitors in the past 12 months prior to screening;
  • Treatment with systemic steroids or systemic cyclosporine in the past 3 months;
  • Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator;
  • Planned surgery within 12 months;
  • Patients who will not be available for study-required visits in the judgment of the Investigator;
  • Current enrollment in another investigational device or drug study;
  • History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer;
  • Estimated life expectancy less than 1 year;
  • Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Denmark,   Netherlands,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03067844
Other Study ID Numbers  ICMJE 2016-01382
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan to make individual participant data available to other researchers.
Current Responsible Party University Hospital Inselspital, Berne
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital Inselspital, Berne
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Lorenz Raeber, Prof., MD Bern Universitiy Hospital
PRS Account University Hospital Inselspital, Berne
Verification Date February 2022

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