Hokusai Study in Pediatric Patients With Confirmed Venous Thromboembolism (VTE)

Phase 3

Completed

Conditions: Venous Thromboembolism (VTE)
Deep Vein Thrombosis (DVT)
Pulmonary Embolism

Interventions: Drug: Standard of Care
Drug: Edoxaban

Registration Number: NCT02798471

Lead Sponsor: Daiichi Sankyo

Brief Summary: This is an event driven Phase 3, prospective, randomized, open-label, blinded endpoint evaluation (PROBE) parallel group study in subjects with confirmed VTE. This study is designed to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of edoxaban and to compare the efficacy and safety of edoxaban against standard of care in pediatric subjects with confirmed VTE.

Detailed Description: The objective is to demonstrate the non-inferiority of edoxaban to standard of care (SOC; including low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors) in the treatment and secondary prevention of VTE in pediatric subjects with regard to the composite efficacy endpoint (ie, symptomatic recurrent VTE, death as result of VTE, and no change or extension of thrombotic burden) during the first 3-month treatment period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 290

Inclusion Criteria

Male or female pediatric subjects between birth (defined as 38 weeks gestational age) and less than 18 years of age at the time of consent.
Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days.
Subjects must have received at least 5 days of heparin therapy prior to randomization to treat the newly identified index VTE. In addition, prior to being randomized to edoxaban or SOC, subjects initially treated with VKA are recommended to have an international normalized ratio (INR) < 2.0.
Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study.
Female subjects who have menarche must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using an approved contraception method throughout the study.

Exclusion Criteria

Subjects with active bleeding or high risk of bleeding contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identified high risk of bleeding during prior experimental administration of DOACs).
Subjects who have been or are being treated with thrombolytic agents, thrombectomy or insertion of a caval filter for the newly identified index VTE.
Administration of antiplatelet therapy is contraindicated in both arms except for low dose aspirin defined as 1-5 mg/Kg/day with maximum of 100 mg/day.
Administration of rifampin is prohibited during the study and subjects on concomitant use of rifampin are excluded.
Subjects with hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk (aPTT > 50 seconds or international normalized ratio [INR] > 2.0 not related to anticoagulation therapy) or alanine aminotransferase (ALT) > 5 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total at Screening Visit.
Subjects with glomerular filtration rate (GFR) < 30% of normal for age and size as determined by the Schwartz formula.
Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed > 99th percentile + 5 mmHg.
Subject with thrombocytopenia < 50 × 109/L at Screening Visit. Subjects with a history of heparin-induced thrombocytopenia may be enrolled in the study at the Investigator's discretion.
Life expectancy less than the expected study treatment duration (3 months).
Subjects who are known to be pregnant or breastfeeding.
Subjects with any condition that, as judged by the Investigator, would place the subject at increased risk of harm if he/she participated in the study, including contraindicated medications.
Subjects who participated in another clinical study or treated with an experimental therapy with less than a 30 day washout period prior to identifying the qualifying index VTE.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule.
Edoxaban	Edoxaban	Edoxaban treatment will be dispensed to the participant on a monthly visit schedule. Edoxaban will be started orally at the age/weight/renal function appropriate dose, depending on the results of the ongoing U157 study (NCT02303431) for the Treatment Period.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	Randomization to Month 3	Diagnosis of recurrent venous thromboembolism (VTE) requires the confirmation by diagnostic imaging and at least one of the symptoms of VTE from such areas as lower or upper extremity, catheter related thrombosis, pulmonary embolism, or sinovenous thrombosis.
Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	Randomization to Month 3	Death from venous thromboembolism (VTE) is based on objective diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out.
Number of Participants With No Change or Extension of Thrombotic Burden During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	Randomization to Month 3	No change or extension of thrombotic burden as assessed by quantitative diagnostic imaging of the index qualifying VTE thrombus at baseline and at Month 3. Imaging criteria for VTE included: - Abnormal compression ultrasonography where compression had been normal or, if non-compressible during screening, an increase in diameter of the thrombus during full compression; - An extension of the echogenic intra-luminal thrombus or absence of flow in the central venous system on Doppler ultrasonography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect, or an extension of non-visualization of veins in the presence of a sudden cut-off on venography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect on computed tomography angiogram (CTA).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Deep Vein Thrombosis, Catheter-related Thrombosis, Sino-venous Thrombosis, and Pulmonary Embolism During the Main, Extension, and Overall Treatment Periods Following Edoxaban or Standard of Care Treatment	From randomization up to Month 12	Deep vein thrombosis was assessed by ultrasonography or magnetic resonance venography (MRV), catheter-related thrombosis was assessed by ultrasonography or echocardiography, sino-venous thrombosis was assessed by brain MRI, and pulmonary embolism was assessed by nuclear ventilation/perfusion (V/Q) scanning.
Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events (On Treatment) During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	Randomization to Month 3	Any bleeding event defined as major and clinically relevant non-major bleeding (CRNM) events was reported. Major bleeding was defined as defined as a composite of any of the following: fatal bleeding; and/or symptomatic bleeding in critical area or organ such as intracranial, intra-spinal, intraocular, retroperitoneal, intra-articular, pulmonary, or pericardial, or intramuscular with compartment syndrome; and/or bleeding that causes a decrease in hemoglobin of at least 2 g/dL or more, or leading to transfusion of the equivalent of two or more units of whole blood or red blood cells. CRNM was defined as acute or sub-acute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: a hospital admission for bleeding; a physician-guided medical or surgical treatment for bleeding or a change in antithrombotic therapy (including interruption or discontinuation of study drug).
Number of Participants With All Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	From randomization up to Month 12	All bleeding events included major bleeding defined as a composite of any of the following: fatal bleeding; and/or symptomatic bleeding in critical area or organ such as intracranial, intra-spinal, intraocular, retroperitoneal, intra-articular, pulmonary, or pericardial, or intramuscular with compartment syndrome; and/or bleeding that causes a decrease in hemoglobin of at least 2 g/dL or more, or leading to transfusion of the equivalent of two or more units of whole blood or red blood cells (RBCs), clinically relevant non-major bleeding defined as acute or sub-acute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: a hospital admission for bleeding; a physician-guided medical or surgical treatment for bleeding or a change in antithrombotic therapy (including interruption or discontinuation of study drug), nuisance bleeding, or a combination of bleeding events.
Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	From randomization up to Month 12	Diagnosis of recurrent venous thromboembolism (VTE) requires the confirmation by diagnostic imaging and at least one of the symptoms of VTE from such areas as lower or upper extremity, catheter related thrombosis, pulmonary embolism, or sinovenous thrombosis.
Number of Participants With Symptomatic Recurrent VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Individual Component of Primary Efficacy Endpoint)	Randomization to Month 3	Diagnosis of recurrent venous thromboembolism (VTE) requires the confirmation by diagnostic imaging and at least one of the symptoms of VTE from such areas as lower or upper extremity, catheter related thrombosis, pulmonary embolism, or sinovenous thrombosis.
Number of Participants Who Died as a Result of VTE During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	From randomization up to Month 12	Death from venous thromboembolism (VTE) is based on objective diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out.
Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Individual Component of Primary Efficacy Endpoint)	Randomization to Month 3	Death from venous thromboembolism (VTE) is based on objective diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out.
Number of Participants With No Change or Extension of Thrombotic Burden During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	From randomization up to Month 12	No change or extension of thrombotic burden as assessed by quantitative diagnostic imaging of the index qualifying VTE thrombus. Imaging criteria for VTE included: - Abnormal compression ultrasonography where compression had been normal or, if non-compressible during screening, an increase in diameter of the thrombus during full compression; - An extension of the echogenic intra-luminal thrombus or absence of flow in the central venous system on Doppler ultrasonography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect, or an extension of non-visualization of veins in the presence of a sudden cut-off on venography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect on computed tomography angiogram (CTA).
Number of Participants With Adjudicated Individual Component of Primary Efficacy Endpoints During the Main Treatment Period Following Edoxaban or Standard of Care Treatment	Randomization to Month 3	Diagnosis of recurrent VTE requires the confirmation imaging and ≥1 symptom of VTE. Death from VTE is based on diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out. No change or extension of thrombotic burden (quantitative diagnostic imaging) of the index qualifying VTE thrombus. Imaging criteria for VTE: - Abnormal compression ultrasonography where compression had been normal or, if non-compressible during screening, an increase in diameter of the thrombus during full compression; - An extension of the echogenic intra-luminal thrombus or absence of flow in the central venous system on Doppler ultrasonography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect, or an extension of non-visualization of veins in the presence of a sudden cut-off on venography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect on computed tomography angiogram (CTA).
Number of Participants Reporting Adjudicated All-Cause Mortality During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated)	From randomization up to Month 12	All-cause mortality is defined as death due to any cause. Adjudicated data are reported for overall all-cause mortality, all-cause mortality by the primary cause of death, and primary cause of death further described by additional specifications.
Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)	From randomization up to Month 12	Any bleeding event defined as major and clinically relevant non-major bleeding (CRNM) events was reported. Major bleeding was defined as defined as a composite of any of the following: fatal bleeding; and/or symptomatic bleeding in critical area or organ such as intracranial, intra-spinal, intraocular, retroperitoneal, intra-articular, pulmonary, or pericardial, or intramuscular with compartment syndrome; and/or bleeding that causes a decrease in hemoglobin of at least 2 g/dL or more, or leading to transfusion of the equivalent of two or more units of whole blood or red blood cells. CRNM was defined as acute or sub-acute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: a hospital admission for bleeding; a physician-guided medical or surgical treatment for bleeding or a change in antithrombotic therapy (including interruption or discontinuation of study drug).

Trial Locations

Locations (140): Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Clinical Hospital Centre Rijeka
🇭🇷
Rijeka, Croatia
Erasmus MC Sophia
🇳🇱
Rotterdam, Netherlands
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
Children's Hospital & Clinics of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
🇧🇷
Curitiba, Paraná, Brazil
Hospital Italiano Regional del Sur
🇦🇷
Buenos Aires, Argentina
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Le Bonheur Childrens Hospital
🇺🇸
Memphis, Tennessee, United States
Stanford University Medical Center
🇺🇸
Stanford, California, United States
UCLA Medical Center CAR
🇺🇸
Los Angeles, California, United States
The Presbyterian Hospital
🇺🇸
Charlotte, North Carolina, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸
Oak Lawn, Illinois, United States
St. Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
CHU Clermont Ferrand - Hôpital d'Estaing
🇫🇷
Clermont-Ferrand, France
Banner University Medical Center
🇺🇸
Tucson, Arizona, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Charite - Campus Virchow-Klinikum
🇩🇪
Berlin, Germany
Semmelweis University 2nd Department of Pediatrics
🇭🇺
Budapest, Hungary
GRAACC - Grupo de Apoio ao Adolescente e à Criança com Câncer
🇧🇷
São Paulo, Brazil
Hospital de Câncer de Barretos - Fundação Pio XII
🇧🇷
Barretos, São Paulo, Brazil
Hospital São Vicente de Paulo
🇧🇷
Passo Fundo, Rio Grande Do Sul, Brazil
Cukurova University Faculty of Medicine Balcali Hospital Pediatry Department
🇹🇷
Adana, Turkey
UMHAT "Sv. Georgi", EAD
🇧🇬
Plovdiv, Bulgaria
Phramongkutklao Hospital
🇹🇭
Bangkok, Thailand
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Children City Clinical Hospital
🇺🇦
Poltava, Ukraine
Hacettepe University Medical Faculty
🇹🇷
Ankara, Turkey
CHU Arnaud de Villeneuve
🇫🇷
Montpellier, France
King Chulalongkorn Memorial Hospital
🇹🇭
Bangkok, Thailand
Songklanagarind Hospital
🇹🇭
Songkhla, Thailand
Debreceni Egyetem Klinikai Kozpont
🇭🇺
Debrecen, Hungary
Hadassah ein Kerem
🇮🇱
Jerusalem, Israel
Istanbul University Istanbul Medical Faculty
🇹🇷
Istanbul, Turkey
Izmir Tepecik Training and Research Hospital
🇹🇷
Izmir, Turkey
Nirmal Hospital
🇮🇳
Surat, Gujarat, India
Ramathibodi Hospital
🇹🇭
Bangkok, Thailand
Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University
🇹🇭
Chiang Mai, Thailand
Srinagarind Hospital
🇹🇭
Khon Kaen, Thailand
CI of Healthcare Regional Children CH Gastroenterology Center Kharkiv NMU
🇺🇦
Kharkiv, Ukraine
Yeditepe University Oncology Hospital
🇹🇷
Istanbul, Turkey
Shree Krishna Hospital & Medical Research Centre, H M Patel Centre for Medical Care and Education
🇮🇳
Karamsad, Gujarat, India
Sir Ganga Ram Hospital
🇮🇳
New Delhi, Delhi, India
Hospital da Cidade de Passo Fundo
🇧🇷
Passo Fundo, Rio Grande Do Sul, Brazil
Instituto de Cardiologia do Rio Grande do Sul
🇧🇷
Pôrto Alegre, Rio Grande Do Sul, Brazil
Shaare Zedek Medical Center
🇮🇱
Jerusalem, Israel
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Hospital Nacional de Niños Benjamín Bloom
🇸🇻
San Salvador, Salvador, El Salvador
Jain Institute of Vascular Sciences
🇮🇳
Bangalore, Karnataka, India
M. S. Ramaiah Medical College and Hospital
🇮🇳
Bangalore, Karnataka, India
Oslo University Hospital
🇳🇴
Oslo, Norway
Christian Medical College
🇮🇳
Ludhiana, Punjab, India
Institute of Child Health
🇮🇳
Kolkata, West Bengal, India
Centro Multidisciplinar de Estudos Clínicos - CEMEC
🇧🇷
Santo André, São Paulo, Brazil
Santa Casa de Votuporanga
🇧🇷
Votuporanga, São Paulo, Brazil
Unidad de Cirugía Cardiovascular de Guatemala (UNICAR)
🇬🇹
Guatemala, Guatemala
KK Women's And Children's Hospital
🇸🇬
Singapore, Singapore
University Medical Centre Ljubljana
🇸🇮
Ljubljana, Slovenia
Taipei Medical University Hospital
🇨🇳
Taipei City, Taiwan
Unidad Nacional de Oncología Pediátrica (UNOP)
🇬🇹
Guatemala, Guatemala
Indraprastha Apollo Hospitals
🇮🇳
Delhi, India
Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santa Marta
🇵🇹
Lisboa, Portugal
Mother and Child Health Care Institute of Serbia "Dr. Vukan Cupic"
🇷🇸
Belgrade, Serbia
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
Ankara Çocuk Sağlığı Ve Hastalıkları Hematoloji Onkoloji Eğitim Araştırma Hastanesi
🇹🇷
Ankara, Turkey
Ege University Medical Faculty
🇹🇷
Izmir, Turkey
Erciyes University Medical Faculty
🇹🇷
Kayseri, Turkey
Mersin University Health Research and Practice Hospital
🇹🇷
Mersin, Turkey
UNIFESP - Universidade Federal de São Paulo
🇧🇷
São Paulo, Brazil
Spectrum Health Helen DeVos Children's Hospital Grand Rapids
🇺🇸
Grand Rapids, Michigan, United States
University North Carolina- Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Indiana Hemophilia and Thrombosis Center
🇺🇸
Indianapolis, Indiana, United States
Sanatorio Allende
🇦🇷
Cordoba, Argentina
IMIP - Instituto de Medicina Integral Professor Fernando Figueira
🇧🇷
Pernambuco, Recife, Brazil
Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP
🇧🇷
Campinas, São Paulo, Brazil
Hospital Samaritano
🇧🇷
São Paulo, Brazil
Levine Children's Hospital Charlotte
🇺🇸
Charlotte, North Carolina, United States
Hospital da Luz Amico Saude LTDA
🇧🇷
São Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷
São Paulo, Brazil
Hospital Infantil Pequeno Príncipe
🇧🇷
São Paulo, Brazil
MHAT - "National Heart Hospital" EAD
🇧🇬
Sofia, Bulgaria
HMCG - Hospital e Maternidade Dr. Christovão da Gama
🇧🇷
São Paulo, Brazil
Edmonton Clinic Health Academy
🇨🇦
Edmonton, Alberta, Canada
MHAT 'Tokuda Hospital Sofia', EAD
🇧🇬
Sofia, Bulgaria
Medical Center for Specialized Ambulatory Medical Assistance for Children's Diseases
🇧🇬
Sofia, Bulgaria
Hospital El Carmen Dr. Luis Valentin Ferrada
🇨🇱
Maipu, Chile
Clinica Las Condes
🇨🇱
Santiago, Chile
McMaster Children's Hospital
🇨🇦
Hamilton, Ontario, Canada
General Hospital Zadar
🇭🇷
Zadar, Croatia
Dětská klinika Fakultní nemocnice
🇨🇿
Hradec Králové, Czechia
CTC Hodonin s.r.o.
🇨🇿
Hodonin, Czechia
Fakultni nemocnice Brno
🇨🇿
Brno, Czechia
University Hospital Pilsen, CZ
🇨🇿
Plzen, Czechia
Ålborg Universitetshospital
🇩🇰
Aalborg, Denmark
Clinical Hospital Centre Cavale Blanche BREST
🇫🇷
Brest, Finistere, France
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
🇫🇷
Pessac, Gironde, France
Hôpital des enfants, CHU Toulouse
🇫🇷
Toulouse, Haute Garonne, France
CHU Rennes - Hopital Sud
🇫🇷
Rennes, Ille Et Vilaine, France
CHU Angers - Hôpital Hôtel Dieu
🇫🇷
Angers, France
Universitaetsklinikum Essen
🇩🇪
Essen, Nordrhein Westfalen, Germany
Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases
🇭🇺
Budapest, Hungary
University of Szeged, Department of Pediatrics
🇭🇺
Szeged, Hungary
Rambam Medical Center
🇮🇱
Haifa, Israel
Government Medical College and Hospital
🇮🇳
Nagpur, Maharashtra, India
Chaim Sheba Medical Center
🇮🇱
Ramat Gan, Israel
Strathmore University Medical Centre
🇰🇪
Nairobi, Kenya
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Gyeonggi-do, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
American University of Beirut Medical Center
🇱🇧
Beirut, Lebanon
Hospital Raja Perempuan Zainab II
🇲🇾
Kota Bharu, Kelantan, Malaysia
Saint George University Hospital Medical Center
🇱🇧
Beirut, Lebanon
Hotel Dieu de France Hospital
🇱🇧
Beirut, Lebanon
INDICASAT AIP Site 7871
🇵🇦
Panamá, Panama
Hospital de Braga
🇵🇹
Braga, Portugal
Hospital da Senhora da Oliveira
🇵🇹
Guimarães, Portugal
INDICASAT AIP Site 7872
🇵🇦
Panamá, Panama
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
🇵🇹
Lisboa, Portugal
S.C Centrul Clinic Mediquest S.R.L
🇷🇴
Sângeorgiu De Mureş, Romania
Russian Scientific Center of Radiology and Nuclear Medicine of Ministry of Health of Russian Federation, Department of Pediatric Oncology
🇷🇺
Moscow, Russian Federation
FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion, FMBA"
🇷🇺
Kirov, Russian Federation
Clinical Center Kragujevac
🇷🇸
Kragujevac, Serbia
National University Hospital
🇸🇬
Singapore, Singapore
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario Virgen Macarena
🇪🇸
Sevilla, Spain
Kaohsiung Veterans General Hospital
🇨🇳
Kaohsiung, Taiwan
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Buddhist Tzu Chi General Hospital
🇨🇳
Hualien City, Taiwan
Hospital Universitario Araba
🇪🇸
Vitoria, Álava, Spain
Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
🇹🇷
Izmir, Turkey
Regional Children's Clinical Hospital
🇺🇦
Dnipro, Ukraine
University of South Florida
🇺🇸
Tampa, Florida, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital Zagreb
🇭🇷
Zagreb, Croatia
University Hospital Centre Zagreb, University of Zagreb School of Medicine
🇭🇷
Zagreb, Croatia
Hasbro Children's Hospital
🇺🇸
Providence, Rhode Island, United States