GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound

NCT ID: NCT01813422

Last Updated: 2019-02-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

970 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-18

Study Completion Date

2016-07-29

Brief Summary

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This study will evaluate whether low-density lipoprotein (LDL-C) lowering with evolocumab (AMG 145) results in greater change from baseline in percent atheroma volume (PAV) at week 78 than placebo in adults with coronary artery disease taking lipid lowering therapy.

Detailed Description

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Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Participants received placebo to evolocumab administered by subcutaneous injection once a month for 76 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered by subcutaneous injection

Evolocumab

Participants received 420 mg evolocumab administered by subcutaneous injection once a month for 76 weeks.

Group Type EXPERIMENTAL

Evolocumab

Intervention Type BIOLOGICAL

Administered by subcutaneous injection

Interventions

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Evolocumab

Administered by subcutaneous injection

Intervention Type BIOLOGICAL

Placebo

Administered by subcutaneous injection

Intervention Type DRUG

Other Intervention Names

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AMG 145 Repatha®

Eligibility Criteria

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Inclusion Criteria

* Clinical indication for coronary angiography
* Subjects already taking statin therapy, niacin or ezetimibe at screening must have been on a stable dose for at least 4 weeks prior to screening LDL-C. Subjects not taking lipid-regulating therapy must enter the study via a lipid stabilization period. Subjects who are intolerant to statins must meet statin intolerance entry criteria
* Fasting LDL-C ≥ 80 mg/dL (2.07 mmol/L) with or without additional risk factors, or, LDL-C ≥ 60 -\< 80 mg/dL (1.55-2.07 mmol/L) in the presence of one major or three minor risk factors

Subjects must meet the following criteria at the qualifying coronary catheterization procedure:

* Evidence of coronary heart disease (at least one lesion in a native coronary artery that has \> 20% reduction in lumen diameter) or prior percutaneous intervention (PCI)
* Left main coronary artery \< 50% reduction in lumen diameter by visual estimation
* Target coronary artery for IVUS must be accessible to the IVUS catheter, must not have a \> 50% reduction in lumen diameter within the target segment (and at least 40 mm in length); cannot have undergone prior PCI or coronary artery bypass graft (CABG) and is not a candidate for intervention over the next 18 months. It may not be a bypass graft, bypassed vessel or culprit vessel for previous myocardial infarction (MI).

Exclusion Criteria

* Coronary artery bypass graft surgery \< 6 weeks prior to the qualifying IVUS
* New York Heart Association (NYHA) III or IV heart failure, or last known left ventricular ejection fraction less than 30%
* Uncontrolled cardiac arrhythmia that is not controlled by medications in the 3 months prior to randomization
* Known hemorrhagic stroke
* Uncontrolled hypertension at randomization
* Fasting Triglycerides ≥ 400 mg/dL (4.5 mmol/L) at screening
* Type 1 diabetes or poorly controlled type 2 diabetes (hemoglobin A1c \[HbA1c\] \> 9%) at screening.
* Moderate to severe renal dysfunction (estimated glomerular filtration rate \[eGFR\] \< 30 ml/min/1.73m²) at screening.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Huntsville, Alabama, United States

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Mobile, Alabama, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Newport Beach, California, United States

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Orange, California, United States

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San Diego, California, United States

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Santa Monica, California, United States

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Torrance, California, United States

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Washington D.C., District of Columbia, United States

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Atlantis, Florida, United States

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Clearwater, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville, Florida, United States

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Melbourne, Florida, United States

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Safety Harbor, Florida, United States

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Atlanta, Georgia, United States

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Hammond, Indiana, United States

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Valparaiso, Indiana, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Covington, Louisiana, United States

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Bethesda, Maryland, United States

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Columbia, Maryland, United States

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Ann Arbor, Michigan, United States

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Bay City, Michigan, United States

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Grand Rapids, Michigan, United States

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Marquette, Michigan, United States

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Midland, Michigan, United States

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Petoskey, Michigan, United States

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Saginaw, Michigan, United States

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Duluth, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Cloud, Minnesota, United States

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Saint Paul, Minnesota, United States

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Columbia, Missouri, United States

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Missoula, Montana, United States

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Omaha, Nebraska, United States

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Ridgewood, New Jersey, United States

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Buffalo, New York, United States

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Johnson City, New York, United States

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Charlotte, North Carolina, United States

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Fargo, North Dakota, United States

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Canton, Ohio, United States

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Elyria, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Hillsboro, Oregon, United States

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Springfield, Oregon, United States

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Doylestown, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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Oak Ridge, Tennessee, United States

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Amarillo, Texas, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Wichita Falls, Texas, United States

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Córdoba, Córdoba Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Concord, New South Wales, Australia

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Darlinghurst, New South Wales, Australia

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Liverpool, New South Wales, Australia

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New Lambton Heights, New South Wales, Australia

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Chermside, Queensland, Australia

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Herston, Queensland, Australia

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Adelaide, South Australia, Australia

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Bedford Park, South Australia, Australia

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Epping, Victoria, Australia

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Footscray, Victoria, Australia

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Heidelberg, Victoria, Australia

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Melbourne, Victoria, Australia

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Nedlands, Western Australia, Australia

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Antwerp, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Hasselt, , Belgium

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Lodelinsart, , Belgium

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Cariacica, Espírito Santo, Brazil

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Goiânia, Goiás, Brazil

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Curitiba, Paraná, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Edmonton, Alberta, Canada

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Victoria, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Saint John, New Brunswick, Canada

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St. John's, Newfoundland and Labrador, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Laval, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Temuco, Cautín, Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Brno, , Czechia

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Hradec Králové, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Ústí nad Labem, , Czechia

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Zlín, , Czechia

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Aarhus N, , Denmark

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Odense C, , Denmark

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Besançon, , France

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Chambray-lès-Tours, , France

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Créteil, , France

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Marseille, , France

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Paris, , France

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Pessac, , France

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Aachen, , Germany

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Essen, , Germany

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München, , Germany

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Neuss, , Germany

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Regensburg, , Germany

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Ulm, , Germany

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Alexandroupoli, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Reykjavik, , Iceland

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Dublin, , Ireland

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Galway, , Ireland

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Hadera, , Israel

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Jerusalem, , Israel

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Rehovot, , Israel

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Novara, , Italy

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Roma, , Italy

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Rozzano MI, , Italy

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Sesto San Giovanni (MI), , Italy

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Torino, , Italy

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Kuantan, Pahang, Malaysia

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George Town, , Malaysia

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Guadalajara, Jalisco, Mexico

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Querétaro City, Querétaro, Mexico

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San Luis Potosí City, San Luis Potosí, Mexico

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Culiacán, Sinaloa, Mexico

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Aguascalientes, , Mexico

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Puebla City, , Mexico

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Alkmaar, , Netherlands

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Amsterdam, , Netherlands

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Amsterdam, , Netherlands

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Eindhoven, , Netherlands

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Leeuwarden, , Netherlands

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Nieuwegein, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Tilburg, , Netherlands

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Utrecht, , Netherlands

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Venlo, , Netherlands

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Zwolle, , Netherlands

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Oslo, , Norway

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Tromsø, , Norway

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Pasig, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Chrzanów, , Poland

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Kędzierzyn-Koźle, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Singapore, , Singapore

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Boksburg, Gauteng, South Africa

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Centurion, Gauteng, South Africa

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Johannesburg, Gauteng, South Africa

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Kuils River, Western Cape, South Africa

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Pinelands, Cape Town, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Daejeon, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Málaga, Andalusia, Spain

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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Santiago de Compostela, Galicia, Spain

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Gijón, Principality of Asturias, Spain

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Madrid, , Spain

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Madrid, , Spain

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Gothenburg, , Sweden

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Helsingborg, , Sweden

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Lund, , Sweden

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Örebro, , Sweden

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Solna, , Sweden

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Stockholm, , Sweden

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Geneva, , Switzerland

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Sankt Gallen, , Switzerland

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Newcastle upon Tyne, , United Kingdom

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Countries

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United States Argentina Australia Belgium Brazil Canada Chile Czechia Denmark France Germany Greece Hungary Iceland Ireland Israel Italy Malaysia Mexico Netherlands Norway Philippines Poland Russia Singapore South Africa South Korea Spain Sweden Switzerland Taiwan United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 27846344 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30336824 (View on PubMed)

Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.

Reference Type DERIVED
PMID: 33078867 (View on PubMed)

Puri R, Nissen SE, Somaratne R, Cho L, Kastelein JJ, Ballantyne CM, Koenig W, Anderson TJ, Yang J, Kassahun H, Wasserman SM, Scott R, Borgman M, Nicholls SJ. Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV). Am Heart J. 2016 Jun;176:83-92. doi: 10.1016/j.ahj.2016.01.019. Epub 2016 Feb 17.

Reference Type DERIVED
PMID: 27264224 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2012-004208-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20120153

Identifier Type: -

Identifier Source: org_study_id

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