A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia

NCT ID: NCT05552326

Last Updated: 2025-10-22

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

446 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-31

Study Completion Date

2025-09-12

Brief Summary

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The purpose of this study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Detailed Description

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This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study in 446 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

Conditions

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Severe Hypertriglyceridemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Olezarsen

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.

Group Type EXPERIMENTAL

Olezarsen

Intervention Type DRUG

Olezarsen will be administered by SC injection.

Placebo

Olezarsen-matching placebo will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through 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

1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
2. Participants must be on lipid-lowering therapy that should adhere to standard of care (SOC) 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.
3. Participants must be willing to comply with diet and lifestyle recommendations as able.

Exclusion Criteria

1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
2. Alanine aminotransferase or aspartate aminotransferase \> 3.0 × upper limit of normal
3. Total bilirubin \> 1.5 ULN unless due to Gilbert's syndrome
4. 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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Central Research Associates, Inc.

Birmingham, Alabama, United States

Site Status

Alabama Clinical Therapeutics, LLC Alabaster

Birmingham, Alabama, United States

Site Status

Onyx Clinical Research

Peoria, Arizona, United States

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NRC Research Institute

Los Angeles, California, United States

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Accel Research Sites

DeLand, Florida, United States

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Finlay Medical Research

Greenacres City, Florida, United States

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University of Florida Jacksonville

Jacksonville, Florida, United States

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Meridien Research

Maitland, Florida, United States

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Columbus Clinical Services

Miami, Florida, United States

Site Status

Harmony Clinical Research, Inc

North Miami Beach, Florida, United States

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Combined Research Orlando Phase I-IV

Orlando, Florida, United States

Site Status

3Sync Research

Sunrise, Florida, United States

Site Status

R & B Medical Center LLC

Tampa, Florida, United States

Site Status

JSV Clinical Research Study, Inc.

Tampa, Florida, United States

Site Status

Metabolic Research Institute

West Palm Beach, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Accel Clinical Research

Eatonton, Georgia, United States

Site Status

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Site Status

Randomize Now

Newnan, Georgia, United States

Site Status

St. Vincent Medical Group

Carmel, Indiana, United States

Site Status

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, United States

Site Status

The Research Group of Lexington, LLC

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Louisville Metabolic and Atherosclerosis Research Center (L-MARC)

Louisville, Kentucky, United States

Site Status

Grace Research, LLC

Bossier City, Louisiana, United States

Site Status

Clinical Trials of America LA, LLC

Monroe, Louisiana, United States

Site Status

University of Maryland School of Medicine

Baltimore, Maryland, United States

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Maryland Cardiovascular Specialists

Baltimore, Maryland, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

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Onyx Clinical Research

Flint, Michigan, United States

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Onyx Clinical Research

Rochester Hills, Michigan, United States

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Stern Cardiovascular

Southaven, Mississippi, United States

Site Status

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status

Orchard Park Family Practice

Orchard Park, New York, United States

Site Status

Clinical Trials of America, LLC

Lenoir, North Carolina, United States

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Diabetes and Endocrinology Consultants, P.C.

Morehead City, North Carolina, United States

Site Status

OnSite Clinical Solutions, LLC

Salisbury, North Carolina, United States

Site Status

The Ohio State University (OSU)

Columbus, Ohio, United States

Site Status

SV Research LLC

Marion, Ohio, United States

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Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

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Main Street Physicians Care Waterway

Little River, South Carolina, United States

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Monument Health Clinical Research

Rapid City, South Dakota, United States

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The Jackson Clinic

Jackson, Tennessee, United States

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Texas Health Family Care

Fort Worth, Texas, United States

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Vilo Research Group

Houston, Texas, United States

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Juno Research

Houston, Texas, United States

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Juno Research

Houston, Texas, United States

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Clinical Trial Network

Houston, Texas, United States

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Pioneer Research Solutions, Inc

Houston, Texas, United States

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Sante Clinical Research, LLC

Kerrville, Texas, United States

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FMC Science

Lampasas, Texas, United States

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DCT - McAllen Primary Care, LLC

McAllen, Texas, United States

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Texas Institute of Cardiology

McKinney, Texas, United States

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SMS Clinical Research, LLC

Mesquite, Texas, United States

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Southern Endocrinology Associates

Mesquite, Texas, United States

Site Status

Permian Research Foundation

Odessa, Texas, United States

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Diabetes & Glandular Disease Clinic, P.A.

San Antonio, Texas, United States

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Tranquil Research

Webster, Texas, United States

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Aspen Clinical Research

Orem, Utah, United States

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Ogden Clinic Grandview

Roy, Utah, United States

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Clinical Investigation Specialists Inc.

Kenosha, Wisconsin, United States

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CIPREC - Centro de Investigación y Prevención Cardiovascular

Buenos Aires, , Argentina

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Fundacion Favaloro

Buenos Aires, , Argentina

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Centro Médico Dra. Laura Maffei

Buenos Aires, , Argentina

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Glenny Corp SA

Buenos Aires, , Argentina

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Instituto de Cardiología Corrientes

Corrientes, , Argentina

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Instituto Médico DAMIC

Córdoba, , Argentina

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Centro Medico San Luis

San Luis, , Argentina

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Clínica FUSAVIM Privada

Villa María, , Argentina

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AZ Sint-Jan Brugge

Bruges, , Belgium

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Hôpital Erasme

Brussels, , Belgium

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Virga Jessa Hospital

Hasselt, , Belgium

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UZ Leuven

Leuven, , Belgium

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NUPEC - Nucleo de Pesquisa Clinica

Belo Horizonte, , Brazil

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Núcleo de Pesquisa Clínica

Curitiba, , Brazil

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Hospital Universitario Walter Cantidio - UFC

Fortaleza, , Brazil

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Nucleo de Pesquisa em Cirurgia Vascular

Porto Alegre, , Brazil

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IBPClin Pesquisa Clinica

Rio de Janeiro, , Brazil

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CPQuali Pesquisa Clinica

São Paulo, , Brazil

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Instituto do Coração - HCFMUSP

São Paulo, , Brazil

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Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP

São Paulo, , Brazil

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i9 Pesquisas Clínicas/Loema - Instituto de Pesquisas Clínica & Consultores

São Paulo, , Brazil

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Medical Center Diamedical EOOD

Dimitrovgrad, , Bulgaria

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MHAT Haskovo AD

Haskovo, , Bulgaria

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MHAT Pazardzhik AD

Pazardzhik, , Bulgaria

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UMHAT - Kaspela EOOD

Plovdiv, , Bulgaria

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University Multiprofile Hospital for Active Treatment Pulmed OOD

Plovdiv, , Bulgaria

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UMHAT Kanev AD

Rousse, , Bulgaria

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MHAT Sliven to MMA Sofia

Sliven, , Bulgaria

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Medical Center Smolyan Clinical Research OOD

Smolyan, , Bulgaria

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Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD

Sofia, , Bulgaria

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Acibadem City Clinic Tokuda University Hospital

Sofia, , Bulgaria

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Medico Dental Center ISUL Tsaritsa Yoanna EOOD

Sofia, , Bulgaria

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Medical Centre Synexus Sofia EOOD

Sofia, , Bulgaria

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Medical Center Zara - Med

Stara Zagora, , Bulgaria

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DCC Equita

Varna, , Bulgaria

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Specialized Hospital for Active Treatment of Cardiology

Varna, , Bulgaria

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Medical Centre "Nevromedics" EOOD

Veliko Tarnovo, , Bulgaria

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NL Health Services

St. John's, Newfoundland and Labrador, Canada

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Aggarwal and Associates Ltd.

Brampton, Ontario, Canada

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Joanne F. Liutkus Medicine Professional Corporation

Cambridge, Ontario, Canada

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Bluewater Clinical Research Group

Sarnia, Ontario, Canada

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Toronto General Hospital

Toronto, Ontario, Canada

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Unite de Recherche Clinique

Saint-Jérôme, Quebec, Canada

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CTC Hodonin s.r.o.

Hodonín, , Czechia

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KardioBusak s.r.o.

Louny, , Czechia

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Fakultni nemocnice v Motole

Prague, , Czechia

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Endokrinologie Cerny Most s.r.o.

Prague, , Czechia

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Diabetologická a endokrinologická ambulance Milan Kvapil

Příbram, , Czechia

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AeskuLab k.s

Teplice, , Czechia

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Hopital de Hautepierre

Strasbourg, , France

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ELSAN - Polyclinique Vauban

Valenciennes, , France

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GHM les Portes du Sud

Vénissieux, , France

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University General Hospital of Alexandroupoli

Alexandroupoli, , Greece

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AHEPA Building of Evaggelismos

Athens, , Greece

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University General Hospital ATTIKON

Athens, , Greece

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Hygeia Hospital

Athens, , Greece

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AHEPA University General Hospital of Thessaloniki

Thessaloniki, , Greece

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Lausmed Kft.

Baja, , Hungary

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DRC Gyogyszervizsgalo Kozpont Kft

Balatonfüred, , Hungary

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Obudai Egeszsegugyi Centrum

Budapest, , Hungary

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Clinexpert Kft.

Budapest, , Hungary

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Pharma4 Trial Kft.

Gyöngyös, , Hungary

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Somogy Varmegyei Kaposi Mor Oktato Korhaz Diabetologiai szakrendeles

Kaposvár, , Hungary

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Max Super Specialty Hospital

New Delhi, National Capital Territory of Delhi, India

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B. M. Birla Heart Research Centre A Unit of the Calcutta Medical Research Institute

Kolkata, West Bengal, India

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Sri Jayadeva Institute of Cardiovascular Sciences and Research

Bengaluru, , India

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Sir Ganga Ram Hospital

Delhi, , India

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Eternal Hospital

Jaipur, , India

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IPGMER

Kolkata, , India

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Vinaya Hospital and Research Centre (A Unit of Karnataka Institute of Medical Sciences)

Mangaluru, , India

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KEM Hospital

Mumbai, , India

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Bhatia Hospital

Mumbai, , India

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Manipal Hospital Mysore

Mysore, , India

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Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, , Italy

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AORN S. Anna e S. Sebastiano UOC FARMACIA

Caserta, , Italy

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Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna

Cona, , Italy

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Fondazione I.R.C.C.S. Policlinico "San Matteo" c/o C.U.R.M.

Pavia, , Italy

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Saules seimons medicinos centras

Kaunas, , Lithuania

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Klinikiniai sprendimai

Kaunas, , Lithuania

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Clinic of Cardiology and Rehabilitation

Klaipėda, , Lithuania

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Republican Panevezys Hospital

Panevezys, , Lithuania

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Pirmoji viltis

Šiauliai, , Lithuania

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Sultanah Bahiyah Hospital

Alor Star, Kedah, Malaysia

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Hospital Taiping

Taiping, Perak, Malaysia

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Pulau Pinang Hospital

George Town, Pulau Pinang, Malaysia

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University Malaya Medical Centre (UMMC)

Kuala Lumpur, , Malaysia

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Medical Care and Research S.A de C.V.

Mérida, Yucatán, Mexico

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Centro de Investigación Cardiométabolica de Aguascalientes S.A. de C.V.

Aguascalientes, , Mexico

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Cientia Investigacion Clinica Sc

Chihuahua City, , Mexico

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Clinstile, S.A. de C.V.

Mexico City, , Mexico

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Clinical Research Institute S.C.

Tlanepantla, , Mexico

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Vumc Amsterdam Medical Center

Amsterdam, , Netherlands

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Gelre Ziekenhuizen Apeldoorn

Apeldoorn, , Netherlands

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Reinier de Graaf Ziekenhuis

Delft, , Netherlands

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Het Van Weel Bethesda ziekenhuis

Dirksland, , Netherlands

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Albert Schweitzer Ziekenhuis

Dordrecht, , 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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UCK, I Klinika Kardiologii

Gdansk, , Poland

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Biokinetica

Józefów, , Poland

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Centrum Medyczne Pratia

Katowice, , Poland

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Centra Medyczne Medyceusz

Lodz, , Poland

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Clinical Best Solutions

Lublin, , Poland

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Etg Lublin

Lublin, , Poland

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Centrum Zdrowia Metabolicznego

Poznan, , Poland

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

Warsaw, , Poland

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Centrum Medycnze AMED

Warsaw, , Poland

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Narodowy Instytut Kardiologii im. S. Wyszyńskiego - PIB

Warsaw, , Poland

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

Zamość, , Poland

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Hospital CUF Tejo

Lisbon, , Portugal

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Centro Hospitalar de Entre Douro e Vouga

Santa Maria da Feira, , Portugal

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Cabinet Medical Individual SC DIANA BARBONTA SRL

Alba, , Romania

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Cardioplus Center SRL

Baia Mare, , Romania

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Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed S.R.L

Brasov, , Romania

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Centrul Medical Medicover Victoria

Bucharest, , Romania

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S.C. SAL MED S.R.L., Cardiologie

Piteşti, , Romania

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Cardio Med SRL

Târgu Mureş, , Romania

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S.C. Mediab Srl

Târgu Mureş, , Romania

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Alian s.r.o.

Bardejov, , Slovakia

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Ambulancia diabetologicka a poruch latkovej premeny a vyzivy

Bratislava, , Slovakia

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Interna a diabetologicka ambulancia - IN-DIA s.r.o.

Lučenec, , Slovakia

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Diab sro

Rožňava, , Slovakia

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Interna SK, s.r.o.

Svidník, , Slovakia

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Areteus s.r.o

Trebišov, , Slovakia

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Hospital Germans Trias i Pujol

Badalona, , Spain

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Hospital Vall d'Hebron

Barcelona, , Spain

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Hospital Comarcal Infanta Elena

Huelva, , Spain

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Hospital Universitario de Jaen

Jaén, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Regional de Malaga

Málaga, , Spain

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Unidad de Ensayos Clinicos

Málaga, , Spain

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Hospital Provincial de Conxo

Santiago de Compostela, , Spain

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Hospital Universitario Virgen Macarena

Seville, , Spain

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Hospital Clinico Universitario de Valencia

Valencia, , Spain

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Hospital Universitario Miguel Servet

Zaragoza, , Spain

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Acardo MedSite

Solna, , Sweden

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, , Taiwan

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Mackay Memorial Hospital

New Taipei City, , Taiwan

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Taichung Veterans General Hospital

Taichung, , Taiwan

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National Cheng Kung University Hospital

Tainan City, , Taiwan

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Shin Kong Wu Ho-Su Memorial Hospital

Taipei, , Taiwan

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Chang Gung Medical Foundation - Linkou Branch

Taoyuan District, , Taiwan

Site Status

Countries

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United States Argentina Belgium Brazil Bulgaria Canada Czechia France Greece Hungary India Italy Lithuania Malaysia Mexico Netherlands Poland Portugal Romania Slovakia Spain Sweden Taiwan

References

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Marston NA, Bergmark BA, Alexander VJ, Karwatowska-Prokopczuk E, Kang YM, Moura FA, Prohaska TA, Zimerman A, Zhang S, Murphy SA, Tsimikas S, Giugliano RP, Sabatine MS. Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia. Am Heart J. 2025 Aug;286:125-135. doi: 10.1016/j.ahj.2025.03.003. Epub 2025 Mar 9.

Reference Type DERIVED
PMID: 40064331 (View on PubMed)

Other Identifiers

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2022-501420-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 678354-CS6

Identifier Type: -

Identifier Source: org_study_id

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