Olorofim Aspergillus Infection Study

NCT ID: NCT05101187

Last Updated: 2026-01-06

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

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-31

Study Completion Date

2026-11-01

Brief Summary

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The purpose of this study is to compare treatment with olorofim versus treatment with AmBisome® followed by standard of care (SOC) in patients with IFD caused by proven IA or probable lower respiratory tract disease Aspergillus species (invasive aspergillosis, IA).

Detailed Description

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The mortality rate in immunosuppressed patients with IA is high even with effective modern antifungal drug treatment. Intrinsic and acquired resistance to azoles and amphotericin B, the two most effective classes of treatment, have been identified in Aspergillus species and are linked to this increased mortality.

Currently marketed antifungal drugs have limitations including limited dosage forms, DDIs, and significant adverse reactions.

For patients with IA who do not respond to or cannot tolerate a triazole therapy, treatment options are even more limited.

Olorofim is an antifungal candidate with a novel mechanism of action offering activity against resistant organisms, differences in safety profile, along with oral dosing, predictable and reliable pharmacokinetic (PK) profile and limited potential for DDIs.

The present study is designed to compare the efficacy, safety, and tolerability of olorofim with that of AmBisome® followed by guideline-based hierarchy standard of care (SOC) in patients with IA whose infection is either refractory to or unsuitable for azole therapy.

Conditions

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Invasive Aspergillosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
Adjudicator and sponsor-blinded.

Study Groups

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Olorofim

Olorofim versus AmBisome followed by Standard of Care (SOC)

Group Type ACTIVE_COMPARATOR

Olorofim

Intervention Type DRUG

Loading Dose: 5 tablets (150 mg) to be taken twice daily at a 12-hour (± 1 hour) interval on Day 1 Maintenance Dose: 3 tablets (90 mg) to be taken twice daily at 12-hour (± 1 hour) intervals from Day 2 until Day 84 (± 7 days)

AmBisome

Olorofim versus AmBisome followed by Standard of Care (SOC)

Group Type ACTIVE_COMPARATOR

AmBisome®

Intervention Type DRUG

Initial course of at least 10 days of AmBisome® administered daily at a dose of 3 mg/kg by IV infusion over a 30- to 60-minute period or according to local guidelines Administration of SOC will follow international, national, or local guidelines and product labelling.

Interventions

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Olorofim

Loading Dose: 5 tablets (150 mg) to be taken twice daily at a 12-hour (± 1 hour) interval on Day 1 Maintenance Dose: 3 tablets (90 mg) to be taken twice daily at 12-hour (± 1 hour) intervals from Day 2 until Day 84 (± 7 days)

Intervention Type DRUG

AmBisome®

Initial course of at least 10 days of AmBisome® administered daily at a dose of 3 mg/kg by IV infusion over a 30- to 60-minute period or according to local guidelines Administration of SOC will follow international, national, or local guidelines and product labelling.

Intervention Type DRUG

Other Intervention Names

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Olorofim (F901318) AmBisome® (liposomal amphotericin B)

Eligibility Criteria

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Inclusion Criteria

1. Male and female patients ages over 18 years and weighing more than 30 kg
2. Patients with proven IA at any site or probable LRTD IA per EORTC/MSG 2019 criteria as adapted for this study and where the duration of specific therapy for this episode of IA has been ≤ 28 days. For purposes of this inclusion, the duration of specific therapy includes any mould-active therapy given for this episode of IA whether subsequently judged potentially effective or not.
3. Patients requiring therapy with an antifungal agent other than a mould-active azole, and who have had ≤ 96 hours of potentially effective prior therapy. Potentially effective prior therapy includes any agent to which the infecting strain of Aspergillus is likely to be susceptible. There are no exclusions or limitations on such agents (eg, AmBisome® is permitted) other than their duration.
4. AmBisome® is an appropriate therapy for the patient.

Exclusion Criteria

1. Women who are pregnant or breastfeeding.
2. Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug
3. Patients with only chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
4. Suspected mucormycosis (zygomycosis).
5. Patients with a known active second fungal infection of any type, other than candidiasis that can be treated with fluconazole.
6. The requirement for ongoing use of echinocandin as Candida prophylaxis.
7. Microbiological findings (eg, bacteriological, virological) or other potential conditions that are temporally related and suggest a different aetiology for the clinical features.
8. Human immunodeficiency virus (HIV) infection but not currently receiving antiretroviral therapy.
9. Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥ 500 msec, or at high risk for QT/QTc prolongation.
10. Evidence of hepatic dysfunction.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iqvia Pty Ltd

INDUSTRY

Sponsor Role collaborator

Shionogi

INDUSTRY

Sponsor Role collaborator

F2G Biotech GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Johan Maertens, MD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California Davis Health System

Sacramento, California, United States

Site Status

UCSF Helen Diller Medical Center at Parnassus Heights

San Francisco, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

NIH Clinical Center ,NIAID,NIH

Bethesda, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Clairvoyant Research Group, LLC

Las Vegas, Nevada, United States

Site Status

Rutgers RWJMS

New Brunswick, New Jersey, United States

Site Status

Weill Cornell Medicine NY Presbyterian Hospital

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke Department of Medicine Infectious Diseases Division

Durham, North Carolina, United States

Site Status

OU Health OU Medical Center

Oklahoma City, Oklahoma, United States

Site Status

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, United States

Site Status

Houston Methodist

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

Royal NorthShore Hospital

Saint Leonards, New South Wales, Australia

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Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

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The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

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Fiona Stanley Hospital

Murdoch, Western Australia, Australia

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AZ Sint-Jan

Bruges, , Belgium

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Hôpital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

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UZ Leuven

Leuven, , Belgium

Site Status

Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Site Status

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Site Status

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Site Status

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba, Paraná, Brazil

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Irmandade da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

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Hospital da Universidade Federal de Santa Maria CEP/UFSM

Santa Maria, Rio Grande do Sul, Brazil

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University of Alberta Hospital

Edmonton, Alberta, Canada

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Hamilton Health Sciences - Juravinski Site

Hamilton, Ontario, Canada

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Toronto General Hospital

Toronto, Ontario, Canada

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University Health Network

Toronto, Ontario, Canada

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The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

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Huazhong University of Science and Technology

Wuhan, Hubei, China

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The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

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Qilu Hospital of Shandong University

Jinan, Shandong, China

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Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, China

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Institute of Hematology and Blood Diseases Hospital

Xiaobailou, Tianjin Municipality, China

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The 1st Affiliated Hosp of Wenzhou Medical University

Wenzhou, Zhejiang, China

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Peking University People's Hospital

Beijing, , China

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Peking University Third Hospital

Beijing, , China

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The First Hospital of Jilin University

Changchun, , China

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Xiangya Hospital, Central South University

Changsha, , China

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Chenzhou No.1 People's Hospital

Chenzhou, , China

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Fujian Medical University Union Hospital

Fuzhou, , China

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Guangdong Provincial People's Hospital

Guangzhou, , China

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The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, , China

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Nanfang Hospital of Southern Medical University

Guangzhou, , China

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The First Affiliated Hospital of Zhejiang University school of medicine

Hangzhou, , China

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Anhui Provincial Hospital

Hefei, , China

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The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, , China

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Shengjing Hospital of China Medical University

Shengyang, , China

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The Second Hospital of Hebei Medical University

Shijiazhuang, , China

Site Status

Xi'an International Medical Center

Xi'an, , China

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Henan Provincial People's Hospital

Zhengzhou, , China

Site Status

Institut de Cancérologie de Strasbourg Europe - ICANS

Strasbourg, Bas Rhin, France

Site Status

CHU Besançon - Hôpital Jean Minjoz

Besançon, Doubs, France

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CHU de Besancon

Besançon, Doubs, France

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CHU Bordeaux Hopital Saint André

Bordeaux, Gironde, France

Site Status

Institut Universitaire du Cancer de Toulouse- IUCT-O

Toulouse, Haute Garonne, France

Site Status

CHU de Rennes - Hôpital Pontchaillou

Rennes, Ille-et-Vilaine, France

Site Status

CHU de Nantes CIC Hematologie

Nantes, Loire Atlantique, France

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Hospital Claude Huriez

Lille, Nord, France

Site Status

Hôpital Necker - Enfants Malades

Paris, Paris, France

Site Status

Universitatsklinikum Leipzig

Leipzig, Saxony, Germany

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Charite Universitatsmedizin Berlin

Berlin, , Germany

Site Status

Universitaetsklinikum Koeln

Cologne, , Germany

Site Status

UKE Universitaetsklinikum-Hamburg Eppendorf

Hamburg-Eppendorf, , Germany

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Soroka University Medical Center

Beersheba, , Israel

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Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

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Chaim Sheba Medical Center

Ramat Gan, , Israel

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Tel Aviv Sourasky Medical Center Pt

Tel Aviv, , Israel

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Azienda Ospedaliera Universitaria Luigi Vanvitelli

Napoli, Campania, Italy

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Fondazione IRCCS San Gerardo dei Tintori

Monza, Di Monza E Della Brianza, Italy

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Istituto Clinico Humanitas

Rozzano, Milano, Italy

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IRCCS Ospedale Policlinico San Martino

Genova, , Italy

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Ospedale San Raffaele

Milan, , Italy

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ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

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AOU Policlinico di Modena

Modena, , Italy

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Clinica Malattie Infettive Dipartimento di Medicina e Chirurgia dell'Università

Perugia, , Italy

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Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello)

Pisa, , Italy

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Inmi Lazzaro Spallanzani Irccs

Roma, , Italy

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Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

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Chiba University Hospital

Chiba, Chiba, Japan

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Kyushu University Hospital

Fukuoka, Fukuoka, Japan

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Tohoku University Hospital

Sendai, Miyagi, Japan

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Osaka International Cancer Institute

Osaka, Osaka, Japan

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Osaka Metropolitan University Hospital

Osaka, Osaka, Japan

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Kindai University Hospital

Ōsaka-sayama, Osaka, Japan

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The Jikei University Hospital

Minato-Ku, Tokyo, Japan

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Toranomon Hospital

Minatoku, Tokyo to, Japan

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Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital

Bunkyō City, , Japan

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Nagasaki University Hospital

Nagasaki, , Japan

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Okayama University Hospital

Okayama, , Japan

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Saitama Medical Center Jichi Medical University

Saitama, , Japan

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Jichi Medical University Hospital

Shimotsuke, , Japan

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Radboud Nijmegen

Nijmegen, , Netherlands

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UMC Utrecht

Utrecht, , Netherlands

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Wellington Regional Hospital

Newtown, Wellington Region, New Zealand

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Auckland City Hospital

Auckland, , New Zealand

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National University Hospital

Singapore, , Singapore

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Singapore General Hospital- Parent

Singapore, , Singapore

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The Catholic University of Korea

Bucheon-si, Seoul, South Korea

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Samsung Medical Center

Irwon-dong, Seoul, South Korea

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Hospital General Universitario Gregorio Marañón

Retiro, Madrid, Spain

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Hospital Universitari Vall d'Hebron

Barcelona, , Spain

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Hospital Clinic de Barcelona

Barcelona, , Spain

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Hospital Universitario Ramon y Cajal

Madrid, , Spain

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Hospital Universitario 12 de Octubre

Madrid, , Spain

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Hospital Universitario La Paz

Madrid, , Spain

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Hospital Universitari i Politecnic La Fe

Valencia, , Spain

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Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

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Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare

New Taipei City, , Taiwan

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China Medical University Hospital

Taichung, , Taiwan

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Taipei Veterans General Hospital

Taipei, , Taiwan

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National Taiwan University Hospital

Taipei, , Taiwan

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Siriraj Hospital

Bangkok Noi, Bangkok, Thailand

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Srinagarind Hospital

Khon Kaen, , Thailand

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Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Dicle University, Medical Faculty

Diyarbakır, , Turkey (Türkiye)

Site Status

Acibadem Atakent Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Site Status

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Site Status

University Hospital of Wales

Cardiff, Wales, United Kingdom

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Kings College Hospital

London, , United Kingdom

Site Status

Imperial College London

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada China France Germany Israel Italy Japan Netherlands New Zealand Singapore South Korea Spain Taiwan Thailand Turkey (Türkiye) United Kingdom

Other Identifiers

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F901318/0041

Identifier Type: -

Identifier Source: org_study_id

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