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

February 23, 2022 updated by: University Hospital Inselspital, Berne

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

294

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria, 1090
        • University Hospital Vienna (AKH)
  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • Netherlands
      • Rotterdam, Netherlands, 3015
        • Erasmus Thoraxcentre
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525
        • Radboud Univerity, Nijmegen Medical Centre
  • Switzerland
      • Basel, Switzerland, 4031
        • Basel University Hospital
      • Bern, Switzerland, 3010
        • Bern University Hospital Inselspital
      • Geneva, Switzerland, 1211
        • Hôpitaux Universitaires Genève
      • Zurich, Switzerland, 8063
        • Stadtspital Triemli
      • Zürich, Switzerland, 8091
        • University Hospital Zurich Usz

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Alirocumab
Alirocumab 150 mg/mL, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
Drug: Alirocumab
Pre-filled auto-injector pen every second week, starting at day 1 and up to week 50
PLACEBO_COMPARATOR: Placebo
Placebo, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
Drug: Alirocumab
Pre-filled auto-injector pen every second week, starting at day 1 and up to week 50

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in percent atheroma volume (PAV)
Time Frame: Baseline to week 52
Change in PAV by greyscale intravascular ultrasound (IVUS)
Baseline to week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in total lipid-core burden index (LCBItotal)
Time Frame: Baseline to week 52
Change in LCBItotal as determined by near infrared spectroscopy (NIRS)
Baseline to week 52
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
Baseline to week 52
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)
Baseline to week 52
Change in mean fibrous cap thickness
Time Frame: Baseline to week 52
Change in mean fibrous cap thickness as determined by OCT
Baseline to week 52
Change in average angular extension (AAE) of macrophages
Time Frame: Baseline to week 52
Change in AAE of macrophages as determined by OCT
Baseline to week 52
Change in normalized total atheroma volume (NTAV)
Time Frame: Baseline to week 52
Change in NTAV by IVUS
Baseline to week 52
Change in LDL-cholesterol
Time Frame: Baseline to week 52
Change in LDL-cholesterol
Baseline to week 52
Change in hsCRP
Time Frame: Baseline to week 52
Change in hsCRP
Baseline to week 52
Change in high sensitivity troponin T (hsTnT)
Time Frame: Baseline to week 52
Change in hsTnT
Baseline to week 52
Change in N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP)
Time Frame: Baseline to week 52
Change in NT-pro-BNP
Baseline to week 52
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
Baseline to week 52
Death
Time Frame: Baseline to week 52
Any death, cardiac death
Baseline to week 52
Non-fatal myocardial infarction
Time Frame: Baseline to week 52
Any non-fatal myocardial infarction
Baseline to week 52
Ischemia-driven coronary revascularization
Time Frame: Baseline to week 52
Any ischemia-driven coronary revascularization
Baseline to week 52
Stroke
Time Frame: Baseline to week 52
Any ischemic stroke/transient ischemic attack
Baseline to week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

Regeneron Pharmaceuticals

Investigators

  • Principal Investigator: Lorenz Raeber, Prof., MD, Bern Universitiy Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 25, 2017

Primary Completion (ACTUAL)

October 13, 2021

Study Completion (ACTUAL)

October 13, 2021

Study Registration Dates

First Submitted

February 24, 2017

First Submitted That Met QC Criteria

February 28, 2017

First Posted (ACTUAL)

March 1, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 24, 2022

Last Update Submitted That Met QC Criteria

February 23, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-01382

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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