CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

NCT ID: NCT04136171

Last Updated: 2025-08-08

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1438 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-13

Study Completion Date

2026-08-31

Brief Summary

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To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC).

Detailed Description

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This is a multicenter, double-blind study in 1438 participants, who will be randomized to receive subcutaneous (SC) injections of either eplontersen or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.

Conditions

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Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Eplontersen

Eplontersen by subcutaneous injection once every 4 weeks

Group Type EXPERIMENTAL

Eplontersen

Intervention Type DRUG

Eplontersen by subcutaneous injection

Placebo

Eplontersen-matching placebo by subcutaneous injection once every 4 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Eplontersen-matching placebo by subcutaneous injection

Interventions

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Eplontersen

Eplontersen by subcutaneous injection

Intervention Type DRUG

Placebo

Eplontersen-matching placebo by subcutaneous injection

Intervention Type DRUG

Other Intervention Names

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ION-682884 IONIS-TTR-LRx

Eligibility Criteria

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Inclusion Criteria

* Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
* Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
* Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid \[DPD-Tc\], 99m Tc-pyrophosphate \[PYP-Tc\], or 99m Tc-hydroxymethylene-diphosphonate \[HMDP-Tc\]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
* End-diastolic interventricular septum thickness of \> 12 millimeters (mm) on Screening echocardiogram
* New York Heart Association (NYHA) class I-III

Exclusion Criteria

* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
* Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
* Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
* Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
* Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid \[siRNA\]; does not apply to COVID-19 mitochondrial \[mRNA\] vaccinations)
* Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

Altman Clinical and Translational Research Institute Center for Clinical Research

La Jolla, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California, San Francisco (UCSF) - Medical Center

San Francisco, California, United States

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Stanford Hospital

Stanford, California, United States

Site Status

University of Colorado Hospital - Anschutz Medical Campus

Aurora, Colorado, United States

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MedStar Washington Hospital Center

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

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The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion

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

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Emory Heart and Vascular Center - Emory Clifton Campus

Atlanta, Georgia, United States

Site Status

Piedmont Heart of Fayetteville

Fayetteville, Georgia, United States

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Northwestern University

Chicago, Illinois, United States

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The University of Chicago Medical Center

Chicago, Illinois, United States

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Loyola University Medical Center

Maywood, Illinois, United States

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Indiana University Health

Indianapolis, Indiana, United States

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University of Kansas Medical Center

Kansas City, Kansas, United States

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Louisiana State University Health Sciences Center

New Orleans, Louisiana, United States

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Tulane University Heart and Vascular Institute

New Orleans, Louisiana, United States

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Ochsner Health System

New Orleans, Louisiana, United States

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University of Maryland Medical Center

Baltimore, Maryland, United States

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Massachusetts General Hospital

Boston, Massachusetts, United States

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Brigham and Women's Hospital

Boston, Massachusetts, United States

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Boston University School of Medicine

Boston, Massachusetts, United States

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Henry Ford Health System

Detroit, Michigan, United States

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Minneapolis Heart Institute

Minneapolis, Minnesota, United States

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Mayo Clinic - Rochester

Rochester, Minnesota, United States

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Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

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Barnes-Jewish Hospital

St Louis, Missouri, United States

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New York University Langone Cardiology Associates

New York, New York, United States

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Columbia University Irving Medical Center

New York, New York, United States

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Weill Cornell Medicine Cardiology

New York, New York, United States

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Laurelton Heart Specialists

Rosedale, New York, United States

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The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

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Duke University Medical Center

Durham, North Carolina, United States

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Carl and Edyth Lindner Research Center at The Christ Hospital

Cincinnati, Ohio, United States

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University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

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Cleveland Clinic Main Campus

Cleveland, Ohio, United States

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The Ohio State University College of Medicine

Columbus, Ohio, United States

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Oregon Health and Science University

Portland, Oregon, United States

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Lancaster General Hospital

Lancaster, Pennsylvania, United States

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Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

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University of Pittsburgh Medical School

Pittsburgh, Pennsylvania, United States

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Medical University of South Carolina

Charleston, South Carolina, United States

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Vanderbilt University Medical Center

Nashville, Tennessee, United States

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University of Texas Southwestern Medical Center

Dallas, Texas, United States

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Houston Methodist Hospital

Houston, Texas, United States

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University of Utah

Salt Lake City, Utah, United States

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Virginia Commonwealth University (VCU)

Richmond, Virginia, United States

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University of Washington

Seattle, Washington, United States

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University of Wisconsin - Madison

Madison, Wisconsin, United States

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Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

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Instituto Cardiovascular de Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Hospital Italiano de Buenos Aires

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

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Liverpool Hospital

Liverpool, New South Wales, Australia

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The Westmead Institute for Medical Research

Westmead, New South Wales, Australia

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Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

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Advara Heartcare

Leabrook, South Australia, Australia

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Royal Hobart Hospital

Hobart, Tasmania, Australia

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Box Hill Hospital

Box Hill, Victoria, Australia

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Advara HeartCare

Joondalup, Western Australia, Australia

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Advara HeartCare Murdoch

Murdoch, Western Australia, Australia

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Medizinische Universität Graz

Graz, Styria, Austria

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Medizinische Universität Innsbruck

Innsbruck, Tyrol, Austria

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Medizinische Universität Wien

Vienna, , Austria

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Ziekenhuis Oost-Limburg - Campus Sint-Jan

Genk, Limburg, Belgium

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Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

Bruges, West-Vlaanderen, Belgium

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Universidade Estadual de Campinas

Campinas, , Brazil

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Hospital Moinhos de Vento

Porto Alegre, , Brazil

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Centro Avançado de Pesquisa e Estudos para o Diagnóstico CAPED

Ribeirão Preto, , Brazil

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Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

Ribeirão Preto, , Brazil

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A Beneficência Portuguesa de São Paulo - Unidade Mirante

São Paulo, , Brazil

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Instituto Dante Pazzanese de Cardiologia

São Paulo, , Brazil

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Instituto do Coração de São Paulo

São Paulo, , Brazil

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University of Calgary

Calgary, Alberta, Canada

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Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

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University Hospital - London Health Sciences Centre

London, Ontario, Canada

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Toronto General Hospital

Toronto, Ontario, Canada

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Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, Canada

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Hôpital Regional de Rimouski

Rimouski, Quebec, Canada

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Fakultní Nemocnice u sv. Anny v Brn

Brno, South Moravian, Czechia

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Vseobecna Fakultni Nemocnice v Praze

Prague, , Czechia

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Institut Klinické a Experimentální Medicíny

Prague, , Czechia

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Rigshospitalet

Copenhagen, Capital Region, Denmark

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Odense Universitetshospital

Odense, Region Syddanmark, Denmark

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Hôpital Rangueil

Toulouse, Occitanie, France

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Hôpitaux Universitaires Henri Mondor

Créteil, , France

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Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, , France

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Hôpital de la Timone

Marseille, , France

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Hôpital Haut-Lévêque

Pessac, , France

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Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec

Saint-Herblain, , France

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Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany

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Charité Campus Mitte

Berlin, , Germany

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Charité Universitätsmedizin Berlin

Berlin, , Germany

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Uniklinik Koln

Cologne, , Germany

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Universitaetsklinikum Heidelberg - Zentrum fur Innere Medizin

Heidelberg, , Germany

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Universitätsklinikum Münster

Münster, , Germany

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Universitätsklinikum Würzburg

Würzburg, , Germany

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Alexandra General Hospital

Athens, , Greece

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Rambam Health Care Campus

Haifa, , Israel

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Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

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Kaplan Medical Center

Rehovot, , Israel

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Azienda Ospedaliero Universitaria Delle Marche

Ancona, , Italy

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Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, , Italy

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Azienda Ospedaliero - Universitaria Careggi

Florence, , Italy

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Azienda Ospedale - Università di Padova

Padua, , Italy

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Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

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Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica

Pisa, , Italy

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Azienda Ospedaliera - Universitaria Sant' Andrea

Roma, , Italy

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Uwajima City Hospital

Uwajima-shi, Ehime, Japan

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Hospital of the University of Occupational and Environmental Health

Kitakyushu-shi, Fukuoka, Japan

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Kurume University Hospital

Kurume-shi, Fukuoka, Japan

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Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

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Saiseikai Fukuoka General Hospital

Fukuoka, Hukuoka, Japan

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Kokura Memorial Hospital

Kitakyushu, Hukuoka, Japan

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University Hospital Kyoto Prefectural University of Medicine

Kyoto, Kyoto, Japan

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Shinshu University Hospital

Matsumoto, Nagano, Japan

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Okayama University Hospital

Okayama, Okayama-ken, Japan

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Osaka Metropolitan University Hospital

Osaka, Osaka, Japan

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Hamamatsu University Hospital

Hamamatsu, Shizuoka, Japan

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Keio University Hospital

Shinjuku-Ku, Tokyo, Japan

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Kumamoto University Hospital

Kumamoto, , Japan

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Krakowski Szpital Specjalistyczny im. Jana Pawa II

Krakow, , Poland

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Narodowy Instytut Kardiologii Stefana kardyna Wyszyskiego - Pastwowy Instytut Badawczy

Warsaw, , Poland

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Hospital da Senhora da Oliveira - Guimarães

Guimarães, , Portugal

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Centro Hospitalar Universitário de Lisboa Central - Hospital de Santa Marta

Lisbon, , Portugal

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Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio

Porto, , Portugal

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Centro Hospitalar Universitário de São João

Porto, , Portugal

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Veterans Affairs Caribbean Healthcare System

San Juan, , Puerto Rico

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Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

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Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, , Spain

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Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, , Spain

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Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, , Spain

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Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

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Skellefteå lasarett

Skellefteå, , Sweden

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Synexus - Scotland Clinical Research Centre

Glasgow, Scotland, United Kingdom

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Synexus - Wales

Cardiff, Wales, United Kingdom

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Synexus Midlands Clinical Research Centre

Edgbaston, , United Kingdom

Site Status

Synexus - North Tees Clinical Research Centre

Hexham, , United Kingdom

Site Status

Synexus - Manchester Clinical Research Centre

Liverpool, , United Kingdom

Site Status

Synexus - Merseyside Clinical Research Centre

Liverpool, , United Kingdom

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Royal Free London NHS Foundation Trust

London, , United Kingdom

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Richmond Pharmacology

London, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Canada Czechia Denmark France Germany Greece Israel Italy Japan Poland Portugal Puerto Rico Spain Sweden United Kingdom

Other Identifiers

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2019-002835-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-514434-20-00

Identifier Type: CTIS

Identifier Source: secondary_id

ION-682884-CS2

Identifier Type: -

Identifier Source: org_study_id

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