A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia

NCT ID: NCT05610280

Last Updated: 2026-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1478 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-21

Study Completion Date

2025-06-09

Brief Summary

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The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.

Detailed Description

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This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period.

The Screening Period was extended with no impact to overall study timelines.

A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.

Conditions

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Hypertriglyceridemia Cardiovascular Diseases Atherosclerosis

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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Olezarsen

Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.

Group Type EXPERIMENTAL

Olezarsen

Intervention Type DRUG

Olezarsen will be administered by SC injection.

Placebo

Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Olezarsen-matching placebo will be administered by SC injection.

Interventions

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Olezarsen

Olezarsen will be administered by SC injection.

Intervention Type DRUG

Placebo

Olezarsen-matching placebo will be administered by SC injection.

Intervention Type DRUG

Other Intervention Names

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ISIS 678354 AKCEA-APOCIII-LRx

Eligibility Criteria

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Inclusion Criteria

* Participants must fall into 1 of the following groups (a or b):

a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 millimoles per liter \[mmol/L\]) and \<500 mg/dL (5.65 mmol/L) with either
* Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or
* At increased risk for ASCVD

b. Severe hypertriglyceridemia with fasting TG ≥500 mg/dL (5.65 mmol/L)
* Participants should be on standard of care (SOC) lipid-lowering medications per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.

Exclusion Criteria

* Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
* Alanine aminotransferase or aspartate aminotransferase \> 3.0 × upper limit of normal
* Total bilirubin \> 1.5 upper limit of normal unless due to Gilbert's syndrome
* Estimated GFR \< 30 mL/min/1.73 m\^2
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Alabama Clinical Therapeutics, LLC Alabaster

Birmingham, Alabama, United States

Site Status

Heart Center Research PC

Huntsville, Alabama, United States

Site Status

Cardiovascular Research Foundation of Southern California

Beverly Hills, California, United States

Site Status

Westside Medical Associates of Los Angeles

Beverly Hills, California, United States

Site Status

Diabetes/Lipid Management & Research Center

Huntington Beach, California, United States

Site Status

University of California, San Diego (UCSD)

La Jolla, California, United States

Site Status

Clinical Trials Research

Lincoln, California, United States

Site Status

Amicis Research

Northridge, California, United States

Site Status

Valley Clinical Trials, Inc.

Northridge, California, United States

Site Status

Northern California Research

Sacramento, California, United States

Site Status

Amicis Research Center

Santa Clarita, California, United States

Site Status

Metabolic Institute of America

Tarzana, California, United States

Site Status

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center

Torrance, California, United States

Site Status

Amicis Research Center

Valencia, California, United States

Site Status

Excel Clinical Medical Trials

Boca Raton, Florida, United States

Site Status

Finlay Medical Research - West Palm

Greenacres City, Florida, United States

Site Status

Global Research Associates

Homestead, Florida, United States

Site Status

3Sync Research

Lake Worth, Florida, United States

Site Status

Finlay Medical Research

Miami, Florida, United States

Site Status

Advanced Medical Research Institute (AMRI)

Miami, Florida, United States

Site Status

De La Cruz Research Center, LL

Miami, Florida, United States

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Suncoast Clinical Research, Inc. - New Port Richey

New Port Richey, Florida, United States

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Suncoast Clinical Research, Inc. - Palm Harbor

New Port Richey, Florida, United States

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Proactive Clinical Research

Oakland Park, Florida, United States

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Ocala Cardiovascular Research

Ocala, Florida, United States

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Comprehensive Medical & Research Center

Plantation, Florida, United States

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Progressive Medical Research

Port Orange, Florida, United States

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St. Johns Center for Clinical Research

Saint Augustine, Florida, United States

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JSV Clinical Research Study, Inc

Tampa, Florida, United States

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Centricity Research

Columbus, Georgia, United States

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Atlanta Heart Specialists

Tucker, Georgia, United States

Site Status

Evanston Premier Healthcare Research LLC

Evanston, Illinois, United States

Site Status

Clinical Investigation Specialists, Inc

Gurnee, Illinois, United States

Site Status

Affinity Health

Park Ridge, Illinois, United States

Site Status

Cardiovascular Research of Northwest Indiana, LLC

Munster, Indiana, United States

Site Status

Reid Hospital and Health Care Services

Richmond, Indiana, United States

Site Status

West Broadway Clinic

Council Bluffs, Iowa, United States

Site Status

Mercy One Iowa Heart Center

West Des Moines, Iowa, United States

Site Status

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, United States

Site Status

Norton Cardiovascular Associates

Louisville, Kentucky, United States

Site Status

Louisville Metabolic and Atherosclerosis Research Center

Louisville, Kentucky, United States

Site Status

Maryland Cardiovascular Specialists

Baltimore, Maryland, United States

Site Status

Aa Mrc, Llc

Flint, Michigan, United States

Site Status

Palm Research Center, Inc.

Las Vegas, Nevada, United States

Site Status

Clinical Research of South Nevada

Las Vegas, Nevada, United States

Site Status

Palm Research Center, Inc.

Las Vegas, Nevada, United States

Site Status

Medical University of South Carolina (MUSC)

Charleston, North Carolina, United States

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Moses H. Cone Memorial Hospital

Greensboro, North Carolina, United States

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Aultman Hospital Cardiology Clinical Trials

Canton, Ohio, United States

Site Status

McConnell Heart Health Center

Columbus, Ohio, United States

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Summit Research Group, LLC

Stow, Ohio, United States

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Central Oklahoma Early Detection Center

Edmond, Oklahoma, United States

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Green and Seidner Family Practice Associates

Lansdale, Pennsylvania, United States

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Main Street Physicians Care Waterway

Little River, South Carolina, United States

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OnSite Clinical Solutions, LLC

Rock Hill, South Carolina, United States

Site Status

Monument Health Clinical Research

Rapid City, South Dakota, United States

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Health Concepts

Rapid City, South Dakota, United States

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The Jackson Clinic

Jackson, Tennessee, United States

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Affinity Health Corp.

Nashville, Tennessee, United States

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Tennessee Center for Clinical Trials

Tullahoma, Tennessee, United States

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Baylor College of Medicine

Houston, Texas, United States

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Juno Research, LLC

Houston, Texas, United States

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Texas Institute of Cardiology

McKinney, Texas, United States

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Southern Endocrinology Associates

Mesquite, Texas, United States

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FMC Science

Round Rock, Texas, United States

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Carient Heart & Vascular

Manassas, Virginia, United States

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Manassas Clinical Research Center

Manassas, Virginia, United States

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Charleston Area Medical Center (CAMC) Clinical Trials Center

Charleston, West Virginia, United States

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MHAT Sv. Ivan Rilski - 2003 OOD

Dupnitsa, , Bulgaria

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University Multiprofile Hospital for Active Treatment Pulmed OOD

Plovdiv, , Bulgaria

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SHATC Medica Cor EAD

Rousse, , Bulgaria

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Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD

Sofia, , Bulgaria

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MBAL National Cardiology Hospital

Sofia, , Bulgaria

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University Multiprofile Hospital for Active Treatment Alexandrovska

Sofia, , Bulgaria

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University Multiprofile Hospital for Active Treatment

Sofia, , Bulgaria

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Medico Dental Center ISUL Tsaritsa Yoanna EOOD

Sofia, , Bulgaria

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UMHAT Prof. Dr. Stoyan Kirkovich

Stara Zagora, , Bulgaria

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Diagnostic Consultative Center Equita (DCC Equita)

Varna, , Bulgaria

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Specialized Hospital for Active Treatment of Cardiology

Varna, , Bulgaria

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ARC Biosystems

Vancouver, British Columbia, Canada

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Centricity Research - Vaughan Endocrinology

Concord, Ontario, Canada

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Centricity Research - Etobicoke Endocrinology

Etobicoke, Ontario, Canada

Site Status

Centricity Research - Oshawa Multispecialty

Oshawa, Ontario, Canada

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Bluewater Clinical Research Group Inc

Sarnia, Ontario, Canada

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Centricity Research - Toronto LMC Multispecialty

Toronto, Ontario, Canada

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Ecogene-21

Chicoutimi, Quebec, Canada

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Montreal Heart Institute - Institut de Cardiologie de Montreal

Montreal, Quebec, Canada

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Institute de Recherches Cliniques de Montreal

Montreal, Quebec, Canada

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Clinique des Maladies Lipidiques de Quebec Inc.

Québec, Quebec, Canada

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Centricity Research - Barrie Endocrinology

Barrie, , Canada

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Centricity Research - Brampton Endocrinology

Brampton, , Canada

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Centre de Recherche Saint-Louis

Québec, , Canada

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UNIVMED s.r.o. - Kardiologicka Ambulance

Brno, , Czechia

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Cevni ambulance - MATMED s.r.o.

Hodonín, , Czechia

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Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod

Jaroměř, , Czechia

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Affidea Praha s.r.o.

Prague, , Czechia

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Diabetologicka a endokrinologicka ambulance Milan Kvapil s.r.o

Prague, , Czechia

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Endokrinologie Cerny Most s.r.o.

Prague, , Czechia

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AeskuLab k.s

Teplice, , Czechia

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MUDr. Nina Zemkova s.r.o. Interni Ambulance

Uherské Hradiště, , Czechia

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Aarhus University Hospital

Aarhus, , Denmark

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Sydvestjysk Hospital

Esbjerg, , Denmark

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Gentofte Hospital

Hellerup, , Denmark

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Godstrup Regional Hospital (Gødstrup)

Herning, , Denmark

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OUH Svendborg Hospital

Svendborg, , Denmark

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Viborg Regional Hospital

Viborg, , Denmark

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HCL Hopital Louis Pradel

Bron, , France

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CHU Dijon Bourgogne - Hopital Francois Mitterrand

Dijon, , France

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AP-HP Hopital Pitie-Salpetriere

Paris, , France

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Groupement de Cooperation Sanitaire (GCS) ELSAN - Polyclinique Vauban

Valenciennes, , France

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GHM les Portes du Sud

Vénissieux, , France

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Clinexpert Kft.

Budapest, , Hungary

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Obudai Egeszsegugyi Centrum

Budapest, , Hungary

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CRU Hungary Kft.

Encs, , Hungary

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IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, , Italy

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ASST NORD MILANO-Ospedale Edoardo Bassini

Cinisello Balsamo, , Italy

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Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna

Cona, , Italy

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Centro Cardiologico Monzino

Milan, , Italy

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ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

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Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, , Italy

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Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Rome, , Italy

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Academic Medical Center - Department of Vascular Medicine

Amsterdam, , Netherlands

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Ziekenhuis Rijnstate

Arnhem, , Netherlands

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Reinier de Graaf Gasthuis

Delft, , Netherlands

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Deventer Ziekenhuis

Deventer, , Netherlands

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Het Van Weel-Bethesda Ziekenhuis

Dirksland, , Netherlands

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Groene Hart Ziekenhuis

Gouda, , Netherlands

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Spaarne Gasthuis

Haarlem, , Netherlands

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Zuyderland Medisch Centrum

Heerlen, , Netherlands

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Bethesda Diabetes Research Center

Hoogeveen, , Netherlands

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Canisius-Wilhelmina Ziekenhuis (CWZ)

Nijmegen, , Netherlands

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D&A Research

Sneek, , Netherlands

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Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

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Maxima Medisch Centrum

Veldhoven, , Netherlands

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Albert Schweitzer Ziekenhuis - Location Dordrecht

Zwijndrecht, , Netherlands

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Albert Schweitzer Ziekenhuis

Zwijndrecht, , Netherlands

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The Lipid Clinic (Oslo University Hospital)

Oslo, , Norway

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SALVIA Lekston i Madej s.j.

Katowice, , Poland

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Jagiellonskie Centrum Innowacji Sp. z o.o.

Krakow, , Poland

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Krakowskie Centrum Medyczne Sp. z o.o.

Krakow, , Poland

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FutureMeds

Lodz, , Poland

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INSTYTUT CENTRUM ZDROWIA MATKI POLKI - Klinika Kardiologii i Wad Wrodzonych Doroslych

Lodz, , Poland

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Praktyka Lekarska Ewa Krzyzagorska

Poznan, , Poland

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FutureMeds Warszawa Centrum

Warsaw, , Poland

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Clinical Best Solutions Sp. z.o.o Spolka Komandytowa

Warsaw, , Poland

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FutureMeds - Centrum Medyczne AMED Warszawa Targowek

Warsaw, , Poland

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Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy, Klinika Kardiologii i Angiologii Interwencyjnej

Warsaw, , Poland

Site Status

FutureMeds Sp. z o.o

Wroclaw, , Poland

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Slaski Park Technologii Medycznych Kardio-Med Silesia Sp. z o. o

Zabrze, , Poland

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ETG Zamosc - Pro Life Medica Sp. z o.o

Zamość, , Poland

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Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz

Carnaxide, , Portugal

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Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz

Lisbon, , Portugal

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Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria

Lisbon, , Portugal

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Centro Hospitalar de Vila Nova de Gaia/Espinho EPE

Vila Nova de Gaia, , Portugal

Site Status

Alian, s.r.o., Kardiologicka ambulancia

Bardejov, , Slovakia

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Cardio D&R, S.R.O. Kosice

Košice, , Slovakia

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Diab sro

Rožňava, , Slovakia

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Interna SK, s.r.o., Kardiologicka a interna ambulancia

Svidník, , Slovakia

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Hospital Abente y Lago

A Coruña, , Spain

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Hospital Germans Trias i Pujol

Badalona, , Spain

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Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

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Calle Villarroel 170

Barcelona, , Spain

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Hospital Universitario Reina Sofia

Córdoba, , Spain

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Hospital Clinico Universitario Virgen de la Arrixaca

El Palmar, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Universitario Virgen de la Victoria

Málaga, , Spain

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Hospital Universitario Virgen Macarena

Seville, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Countries

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United States Bulgaria Canada Czechia Denmark France Hungary Italy Netherlands Norway Poland Portugal Slovakia Spain

References

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Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Kang YM, Weinland J, Murphy SA, Goodrich EL, Zhang S, Li D, Banach M, Stroes E, Lu MT, Tsimikas S, Giugliano RP, Sabatine MS; Essence-TIMI 73b Investigators. Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. N Engl J Med. 2025 Oct 2;393(13):1279-1291. doi: 10.1056/NEJMoa2507227. Epub 2025 Aug 30.

Reference Type DERIVED
PMID: 40888739 (View on PubMed)

Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Kang YM, Murphy SA, Zhang S, Lu MT, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS. Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence-TIMI 73b trial. Am Heart J. 2025 Aug;286:116-124. doi: 10.1016/j.ahj.2025.02.022. Epub 2025 Mar 11.

Reference Type DERIVED
PMID: 40081744 (View on PubMed)

Other Identifiers

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2022-501486-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 678354-CS9

Identifier Type: -

Identifier Source: org_study_id

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