Clinical trial NCT01813422: GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound
Official title: A Double-blind, Randomized, Multi-center, Placebo-controlled, Parallel-group Study to Determine the Effects of Evolocumab (AMG 145) Treatment on Atherosclerotic Disease Burden as Measured by Intravascular Ultrasound in Subjects Undergoing Coronary Catheterization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Cholesterol
High Cholesterol
Elevated Cholesterol
Raised Cholesterol
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-03-19
Enrollment: 970
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Percent Atheroma Volume at Week 78
timeFrame: Baseline and week 78
Secondary outcomes:
measure: Change From Baseline in Total Atheroma Volume at Week 78
timeFrame: Baseline and week 78
measure: Percentage of Participants With Regression in Percent Atheroma Volume
timeFrame: Baseline and week 78
measure: Percentage of Participants With Regression in Total Atheroma Volume
timeFrame: Baseline and week 78
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: La Jolla
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
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state: California
city: Santa Monica
country: United States
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state: California
city: Torrance
country: United States
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state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Atlantis
country: United States
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state: Florida
city: Clearwater
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Jacksonville
country: United States
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state: Florida
city: Melbourne
country: United States
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state: Florida
city: Safety Harbor
country: United States
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state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Hammond
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state: Indiana
city: Valparaiso
country: United States
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state: Indiana
city: Lexington
country: United States
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state: Kentucky
city: Louisville
country: United States
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state: Kentucky
city: Covington
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state: Louisiana
city: Bethesda
country: United States
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state: Maryland
city: Columbia
country: United States
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state: Maryland
city: Ann Arbor
country: United States
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state: Michigan
city: Bay City
country: United States
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state: Michigan
city: Grand Rapids
country: United States
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state: Michigan
city: Marquette
country: United States
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city: Midland
country: United States
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city: Petoskey
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city: Saginaw
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city: Duluth
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city: Minneapolis
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city: Saint Cloud
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city: Saint Paul
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city: Missoula
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city: Omaha
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city: Ridgewood
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city: Johnson City
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city: Charlotte
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state: North Carolina
city: Fargo
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city: Canton
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city: Elyria
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city: Toledo
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city: Oklahoma City
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city: San Antonio
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city: Wichita Falls
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state: Texas
city: Ciudad Autonoma de Buenos Aires
country: Argentina
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state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
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state: Buenos Aires
city: La Plata
country: Argentina
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state: Buenos Aires
city: Cordoba
country: Argentina
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state: Córdoba
city: Cordoba
country: Argentina
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city: Rosario
country: Argentina
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state: Santa Fe
city: Buenos Aires
country: Argentina
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country: Argentina
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country: Argentina
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city: Concord
country: Australia
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state: New South Wales
city: Darlinghurst
country: Australia
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city: Liverpool
country: Australia
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city: New Lambton Heights
country: Australia
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state: New South Wales
city: Chermside
country: Australia
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state: Queensland
city: Herston
country: Australia
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state: Queensland
city: Adelaide
country: Australia
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state: South Australia
city: Bedford Park
country: Australia
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state: South Australia
city: Epping
country: Australia
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state: Victoria
city: Footscray
country: Australia
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state: Victoria
city: Heidelberg
country: Australia
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state: Victoria
city: Melbourne
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state: Victoria
city: Nedlands
country: Australia
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state: Western Australia
city: Antwerpen
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
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city: Edegem
country: Belgium
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city: Genk
country: Belgium
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city: Gent
country: Belgium
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city: Hasselt
country: Belgium
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city: Lodelinsart
country: Belgium
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city: Cariacica
country: Brazil
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state: Espírito Santo
city: Goiania
country: Brazil
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city: Curitiba
country: Brazil
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state: Paraná
city: Porto Alegre
country: Brazil
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state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
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state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
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country: Canada
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city: Edmonton
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city: Victoria
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city: Winnipeg
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city: Saint John
country: Canada
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city: St. Johns
country: Canada
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state: Newfoundland and Labrador
city: Halifax
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city: London
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city: Toronto
country: Canada
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city: Toronto
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city: Laval
country: Canada
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state: Quebec
city: Montreal
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city: Montreal
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city: Montreal
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city: Quebec City
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city: Temuco
country: Chile
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state: Cautín
city: Santiago
country: Chile
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country: Chile
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country: Chile
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country: Czechia
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city: Hradec Kralove
country: Czechia
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city: Praha 2
country: Czechia
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country: Czechia
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country: Czechia
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city: Aarhus N
country: Denmark
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city: Odense C
country: Denmark
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city: Besançon Cedex
country: France
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city: Chambray les Tours
country: France
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country: France
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city: Marseille cedex 5
country: France
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city: Paris
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country: France
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city: Aachen
country: Germany
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city: Essen
country: Germany
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city: München
country: Germany
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city: Neuss
country: Germany
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city: Regensburg
country: Germany
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city: Ulm
country: Germany
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city: Alexandroupoli
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
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country: Greece
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city: Heraklion
country: Greece
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Debrecen
country: Hungary
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city: Pecs
country: Hungary
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city: Szeged
country: Hungary
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city: Reykjavik
country: Iceland
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country: Ireland
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country: Ireland
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city: Hadera
country: Israel
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country: Israel
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country: Israel
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city: Novara
country: Italy
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city: Roma
country: Italy
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city: Rozzano MI
country: Italy
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city: Sesto San Giovanni (MI)
country: Italy
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city: Torino
country: Italy
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city: Daejeon
country: Korea, Republic of
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city: Seongnam-si
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Kuantan
country: Malaysia
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state: Pahang
city: Penang
country: Malaysia
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country: Mexico
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state: Jalisco
city: Queretaro
country: Mexico
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city: San Luis Potosi
country: Mexico
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state: San Luis Potosí
city: Culiacan
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city: Aguascalientes
country: Mexico
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country: Mexico
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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country: Netherlands
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city: Tilburg
country: Netherlands
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city: Utrecht
country: Netherlands
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city: Venlo
country: Netherlands
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city: Zwolle
country: Netherlands
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Tromso
country: Norway
facility: Research Site
city: Pasig City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Chrzanow
country: Poland
facility: Research Site
city: Kedzierzyn Kozle
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Kemerovo
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Boksburg
country: South Africa
facility: Research Site
state: Gauteng
city: Centurion
country: South Africa
facility: Research Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Kuils River
country: South Africa
facility: Research Site
state: Western Cape
city: Pinelands, Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Somerset West
country: South Africa
facility: Research Site
state: Western Cape
city: Malaga
country: Spain
facility: Research Site
state: Andalucía
city: Gijon
country: Spain
facility: Research Site
state: Asturias
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: L Hospitalet De Llobregat
country: Spain
facility: Research Site
state: Cataluña
city: Santiago de Compostela
country: Spain
facility: Research Site
state: Galicia
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Helsingborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Solna
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
city: Geneva 14
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.