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Coronary VesselPhase 3PACMAN-AMINCT03067844

Vascular Effects of Alirocumab in Acute MI-Patients

A Phase 3 study testing Alirocumab in people with Coronary Vessel and Coronary Circulation, run by Insel Gruppe AG, University Hospital Bern at 9 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alirocumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
294 participants
Where
9 sitesin 4 countries
Study dates
25 Apr 2017to 13 Oct 2021
Phase
Phase 3
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 11Show fewer
  • 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.

Who cannot join

  • 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;
Show all 22Show fewer
  • 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.

Trial locations and contacts

9 sites in 4 countries.

9 sites in 4 countries

Switzerland5 sites

  • Basel University Hospital

    Basel, 4031

  • Bern University Hospital Inselspital

    Bern, 3010

  • Hopitaux Universitaires Geneve

    Geneva, 1211

  • Stadtspital Triemli

    Zurich, 8063

  • University Hospital Zurich USZ

    Zurich, 8091

Other trials in Switzerland

Netherlands2 sites

  • Radboud Univerity, Nijmegen Medical Centre

    Nijmegen, Gelderland, 6525

  • Erasmus Thoraxcentre

    Rotterdam, 3015

Other trials in Netherlands

Austria1 site

  • University Hospital Vienna (AKH)

    Vienna, 1090

Other trials in Austria

Denmark1 site

  • Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

About this study

Official title: 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.

Read the 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
Being tested
Alirocumab
Medical subject headings
Plaque, Atherosclerotic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlirocumabDrug

    Pre-filled auto-injector pen every second week, starting at day 1 and up to week 50

Study groups in NCT03067844
Study groupRoleWhat they receive
AlirocumabExperimentalAlirocumab 150 mg/mL, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
Receives: Drug: Alirocumab
PlaceboPlacebo comparatorPlacebo, pre-filled auto-injector pen, every second week, starting at day 1 and up to week 50.
Receives: Drug: Alirocumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in percent atheroma volume (PAV)

    Change in PAV by greyscale intravascular ultrasound (IVUS)

    Measured: Baseline to week 52

Secondary outcomes (15)

  1. Change in total lipid-core burden index (LCBItotal)

    Change in LCBItotal as determined by near infrared spectroscopy (NIRS)

    Measured: Baseline to week 52

  2. Change in maximum LCBI in any 4-mm segment (Powered)

    Change in maximum LCBI in any 4-mm segment (maxLCBI4mm) as determined by NIRS

    Measured: Baseline to week 52

  3. Change in minimal fibrous cap thickness (Powered)

    Change in minimal fibrous cap thickness as determined by optical coherence tomography (OCT)

    Measured: Baseline to week 52

  4. Change in mean fibrous cap thickness

    Change in mean fibrous cap thickness as determined by OCT

    Measured: Baseline to week 52

  5. Change in average angular extension (AAE) of macrophages

    Change in AAE of macrophages as determined by OCT

    Measured: Baseline to week 52

  6. Change in normalized total atheroma volume (NTAV)

    Change in NTAV by IVUS

    Measured: Baseline to week 52

  7. Change in LDL-cholesterol

    Change in LDL-cholesterol

    Measured: Baseline to week 52

  8. Change in hsCRP

    Change in hsCRP

    Measured: Baseline to week 52

  9. Change in high sensitivity troponin T (hsTnT)

    Change in hsTnT

    Measured: Baseline to week 52

  10. Change in N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP)

    Change in NT-pro-BNP

    Measured: Baseline to week 52

  11. Change in further biomarkers

    Change in lipid and inflammatory markers and their association with indices of plaque progression/regression

    Measured: Baseline to week 52

  12. Death

    Any death, cardiac death

    Measured: Baseline to week 52

  13. Non-fatal myocardial infarction

    Any non-fatal myocardial infarction

    Measured: Baseline to week 52

  14. Ischemia-driven coronary revascularization

    Any ischemia-driven coronary revascularization

    Measured: Baseline to week 52

  15. Stroke

    Any ischemic stroke/transient ischemic attack

    Measured: Baseline to week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2017
  2. Study start25 Apr 2017
  3. Primary completion13 Oct 2021
  4. Study completion13 Oct 2021

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
294 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03067844
Sponsor's protocol ID
2016-01382
Other IDs
2016
Acronym
PACMAN-AMI
Status last verified
Feb 2022
First submitted
24 Feb 2017
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No plan to make individual participant data available to other researchers.

Publications

  • Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJP, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Honda S, Shishikura D, Scherer DJ, Borgman M, Brennan DM, Wolski K, Nissen SE. Effect of Evolocumab on Coronary Plaque Composition. J Am Coll Cardiol. 2018 Oct 23;72(17):2012-2021. doi: 10.1016/j.jacc.2018.06.078.

    PubMed 30336824

  • Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, Wasserman SM, Scott R, Ungi I, Podolec J, Ophuis AO, Cornel JH, Borgman M, Brennan DM, Nissen SE. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016 Dec 13;316(22):2373-2384. doi: 10.1001/jama.2016.16951.

    PubMed 27846344

  • Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934. doi: 10.1016/j.jacc.2013.11.002. Epub 2013 Nov 12. No abstract available.

    PubMed 24239923

  • Cannon CP, Cariou B, Blom D, McKenney JM, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM; ODYSSEY COMBO II Investigators. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015 May 14;36(19):1186-94. doi: 10.1093/eurheartj/ehv028. Epub 2015 Feb 16.

    PubMed 25687353

  • Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.

    PubMed 26330422

  • Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1489-99. doi: 10.1056/NEJMoa1501031. Epub 2015 Mar 15.

    PubMed 25773378

  • Koskinas KC, Ughi GJ, Windecker S, Tearney GJ, Raber L. Intracoronary imaging of coronary atherosclerosis: validation for diagnosis, prognosis and treatment. Eur Heart J. 2016 Feb 7;37(6):524-35a-c. doi: 10.1093/eurheartj/ehv642. Epub 2015 Dec 11.

    PubMed 26655874

  • Raber L, Taniwaki M, Zaugg S, Kelbaek H, Roffi M, Holmvang L, Noble S, Pedrazzini G, Moschovitis A, Luscher TF, Matter CM, Serruys PW, Juni P, Garcia-Garcia HM, Windecker S; IBIS 4 (Integrated Biomarkers and Imaging Study-4) Trial Investigators (NCT00962416). Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study. Eur Heart J. 2015 Feb 21;36(8):490-500. doi: 10.1093/eurheartj/ehu373. Epub 2014 Sep 2.

    PubMed 25182248

  • Pu J, Mintz GS, Brilakis ES, Banerjee S, Abdel-Karim AR, Maini B, Biro S, Lee JB, Stone GW, Weisz G, Maehara A. In vivo characterization of coronary plaques: novel findings from comparing greyscale and virtual histology intravascular ultrasound and near-infrared spectroscopy. Eur Heart J. 2012 Feb;33(3):372-83. doi: 10.1093/eurheartj/ehr387. Epub 2011 Oct 20.

    PubMed 22019821

  • Maehara A, Cristea E, Mintz GS, Lansky AJ, Dressler O, Biro S, Templin B, Virmani R, de Bruyne B, Serruys PW, Stone GW. Definitions and methodology for the grayscale and radiofrequency intravascular ultrasound and coronary angiographic analyses. JACC Cardiovasc Imaging. 2012 Mar;5(3 Suppl):S1-9. doi: 10.1016/j.jcmg.2011.11.019.

    PubMed 22421222

  • Madder RD, Goldstein JA, Madden SP, Puri R, Wolski K, Hendricks M, Sum ST, Kini A, Sharma S, Rizik D, Brilakis ES, Shunk KA, Petersen J, Weisz G, Virmani R, Nicholls SJ, Maehara A, Mintz GS, Stone GW, Muller JE. Detection by near-infrared spectroscopy of large lipid core plaques at culprit sites in patients with acute ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2013 Aug;6(8):838-46. doi: 10.1016/j.jcin.2013.04.012. Epub 2013 Jul 17.

    PubMed 23871513

  • Raber L, Zanchin T, Baumgartner S, Taniwaki M, Kalesan B, Moschovitis A, Garcia-Garcia HM, Justiz J, Pilgrim T, Wenaweser P, Meier B, Juni P, Windecker S. Differential healing response attributed to culprit lesions of patients with acute coronary syndromes and stable coronary artery after implantation of drug-eluting stents: an optical coherence tomography study. Int J Cardiol. 2014 May 1;173(2):259-67. doi: 10.1016/j.ijcard.2014.02.036. Epub 2014 Feb 28.

    PubMed 24631113

  • Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho JM, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Dudek D, Falk E, Feldman MD, Fitzgerald P, Garcia-Garcia HM, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietrasik A, Prati F, Raber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G; International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT). Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012 Mar 20;59(12):1058-72. doi: 10.1016/j.jacc.2011.09.079.

    PubMed 22421299

  • Schmidt LE, Burnap SA, Singh B, Takov K, Losdat S, Schrutka L, Galli L, Theofilatos K, Otto GW, Hengstenberg C, Tzoulaki I, Lang IM, Koskinas KC, Speidl WS, Raber L, Mayr M. Integrative Proteomic and Lipidomic Analysis of Patients With Acute Myocardial Infarction Treated With PCSK9 Antibodies and Statins. Circ Genom Precis Med. 2026 Apr;19(2):e005345. doi: 10.1161/CIRCGEN.125.005345. Epub 2026 Feb 10.

    PubMed 41664920

  • van der Velpen V, Haner JD, Kakizaki R, Bar S, Ueki Y, Siontis GCM, Stortecky S, Biccire FG, Ambuhl M, Kaiser C, Iglesias JF, Mach F, van Geuns RJ, Daemen J, Engstrom T, Ondracek AS, Lang I, Bourantas CV, Matter CM, Windecker S, Koskinas KC, Mayr M, Losdat S, Raber L, Haschke M, Spirk D. Intake of high-intensity statin after acute myocardial infarction assessed by direct drug concentration measurement: association with LDL-C response and coronary plaque modifications in the PACMAN-AMI trial. Eur J Prev Cardiol. 2025 Aug 12:zwaf457. doi: 10.1093/eurjpc/zwaf457. Online ahead of print.

    PubMed 40796144

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alirocumab in people with Coronary Vessel and Coronary Circulation, run by Insel Gruppe AG, University Hospital Bern at 9 sites in 4 countries.

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 11 inclusion and 22 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 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Switzerland, Netherlands, Austria, Denmark. 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 percent atheroma volume (PAV) (time frame: Baseline to week 52). 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 NCT03067844, which also lists 22 linked publications.

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 24 Feb 2022.

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