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

• ClinicalTrials.gov Identifier: NCT02798471
• Recruitment Status: Completed
• First Posted: June 14, 2016
• Results First Posted: March 6, 2023
• Last Update Posted: March 6, 2023
• Sponsor: Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism (VTE); Pulmonary Embolism; Deep Vein Thrombosis (DVT)	Drug: Edoxaban; Drug: Standard of Care	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 290 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-label, Randomized, Multi-center, Controlled Trial to Evaluate the Pharmacokinetics and Pharmacodynamics of Edoxaban and to Compare the Efficacy and Safety of Edoxaban With Standard of Care Anticoagulant Therapy in Pediatric Subjects From Birth to Less Than 18 Years of Age With Confirmed Venous Thromboembolism (VTE)
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: May 24, 2022
• Actual Study Completion Date: May 24, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Edoxaban; 15 or 30 mg tablets for participants 12 years of age to <18, and 60 mg edoxaban suspension for oral administration to participants under 12 years of age
Experimental: Standard of Care; Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule.	Drug: Standard of Care; Standard of care could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors.; Other Names: Warfarin/heparin; Enoxaparin; Fondaparinux

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite) [ Time Frame: 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.
2. Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite) [ Time Frame: 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.
3. 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) [ Time Frame: 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 :

1. Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite) [ Time Frame: 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.
2. 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) [ Time Frame: 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.
3. Number of Participants Who Died as a Result of VTE During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite) [ Time Frame: 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.
4. 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) [ Time Frame: 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.
5. 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) [ Time Frame: 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).
6. Number of Participants With Adjudicated Individual Component of Primary Efficacy Endpoints During the Main Treatment Period Following Edoxaban or Standard of Care Treatment [ Time Frame: 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).
7. Number of Participants Reporting Adjudicated All-Cause Mortality During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated) [ Time Frame: 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.
8. 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 [ Time Frame: 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.
9. 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) [ Time Frame: 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).
10. Number of Participants With All Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite) [ Time Frame: 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.
11. 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) [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 1 Day to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.
2. Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days.
3. 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.
4. 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.
5. 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:

1. 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).
2. Subjects who have been or are being treated with thrombolytic agents, thrombectomy or insertion of a caval filter for the newly identified index VTE.
3. 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.
4. Administration of rifampin is prohibited during the study and subjects on concomitant use of rifampin are excluded.
5. 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.
6. Subjects with glomerular filtration rate (GFR) < 30% of normal for age and size as determined by the Schwartz formula.
7. Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed > 99th percentile + 5 mmHg.
8. 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.
9. Life expectancy less than the expected study treatment duration (3 months).
10. Subjects who are known to be pregnant or breastfeeding.
11. 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.
12. 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.

Contacts and Locations

Locations

United States, Arizona

Banner University Medical Center

Tucson, Arizona, United States, 85724

United States, California

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

UCLA Medical Center CAR

Los Angeles, California, United States, 90095

Stanford University Medical Center

Stanford, California, United States, 94305-2200

United States, Florida

University of Miami Miller School of Medicine

Miami, Florida, United States, 33136

University of South Florida

Tampa, Florida, United States, 33606

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States, 60453-2699

United States, Indiana

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States, 46260

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Michigan

Spectrum Health Helen DeVos Children's Hospital Grand Rapids

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Children's Hospital & Clinics of Minnesota

Minneapolis, Minnesota, United States, 55404

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, North Carolina

University North Carolina- Chapel Hill

Chapel Hill, North Carolina, United States, 27517

Levine Children's Hospital Charlotte

Charlotte, North Carolina, United States, 28204

The Presbyterian Hospital

Charlotte, North Carolina, United States, 28210

East Carolina University

Greenville, North Carolina, United States, 27858

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Rhode Island

Hasbro Children's Hospital

Providence, Rhode Island, United States, 02903

United States, Tennessee

Le Bonheur Childrens Hospital

Memphis, Tennessee, United States, 38105

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Wisconsin

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226-4874

Argentina

Hospital Italiano Regional del Sur

Buenos Aires, Argentina, B8001HXM

Sanatorio Allende

Cordoba, Argentina, X5000JHQ

Brazil

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba, Paraná, Brazil, 81520-060

IMIP - Instituto de Medicina Integral Professor Fernando Figueira

Pernambuco, Recife, Brazil, 50070-550

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080

Hospital da Cidade de Passo Fundo

Passo Fundo, Rio Grande Do Sul, Brazil, 99010-260

Instituto de Cardiologia do Rio Grande do Sul

Pôrto Alegre, Rio Grande Do Sul, Brazil, 90620-001

Hospital de Câncer de Barretos - Fundação Pio XII

Barretos, São Paulo, Brazil, 14784-400

Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP

Campinas, São Paulo, Brazil, 13083-878

Centro Multidisciplinar de Estudos Clínicos - CEMEC

Santo André, São Paulo, Brazil, 09190-510

Santa Casa de Votuporanga

Votuporanga, São Paulo, Brazil, 15500-003

Hospital Samaritano

São Paulo, Brazil, 01232-010

Hospital da Luz Amico Saude LTDA

São Paulo, Brazil, 04013-060

Hospital Infantil Pequeno Príncipe

São Paulo, Brazil, 04013-060

GRAACC - Grupo de Apoio ao Adolescente e à Criança com Câncer

São Paulo, Brazil, 04039-001

UNIFESP - Universidade Federal de São Paulo

São Paulo, Brazil, 04039-032

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, Brazil, 05403-000

HMCG - Hospital e Maternidade Dr. Christovão da Gama

São Paulo, Brazil, 09030-010

Bulgaria

UMHAT "Sv. Georgi", EAD

Plovdiv, Bulgaria, 4000

MHAT - "National Heart Hospital" EAD

Sofia, Bulgaria, 1309

MHAT 'Tokuda Hospital Sofia', EAD

Sofia, Bulgaria, 1407

Medical Center for Specialized Ambulatory Medical Assistance for Children's Diseases

Sofia, Bulgaria, 1612

Canada, Alberta

Edmonton Clinic Health Academy

Edmonton, Alberta, Canada, T6G 2B7

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Ontario

McMaster Children's Hospital

Hamilton, Ontario, Canada, L8N 3Z5

Chile

Hospital El Carmen Dr. Luis Valentin Ferrada

Maipu, Chile, 9251521

Clinica Las Condes

Santiago, Chile, 7591047

Croatia

Clinical Hospital Centre Rijeka

Rijeka, Croatia, 51000

General Hospital Zadar

Zadar, Croatia, 23000

Children's Hospital Zagreb

Zagreb, Croatia, 10 000

University Hospital Centre Zagreb, University of Zagreb School of Medicine

Zagreb, Croatia, 10000

Czechia

Fakultni nemocnice Brno

Brno, Czechia, 613 00

CTC Hodonin s.r.o.

Hodonin, Czechia, 69501

Dětská klinika Fakultní nemocnice

Hradec Králové, Czechia, 500 05

University Hospital Pilsen, CZ

Plzen, Czechia, 305 99

Denmark

Ålborg Universitetshospital

Aalborg, Denmark, 9000

El Salvador

Hospital Nacional de Niños Benjamín Bloom

San Salvador, Salvador, El Salvador

France

Clinical Hospital Centre Cavale Blanche BREST

Brest, Finistere, France, 29200

Groupe Hospitalier Sud - Hôpital Haut-Lévêque

Pessac, Gironde, France, 33600

Hôpital des enfants, CHU Toulouse

Toulouse, Haute Garonne, France, 31059

CHU Rennes - Hopital Sud

Rennes, Ille Et Vilaine, France, 35203

CHU Angers - Hôpital Hôtel Dieu

Angers, France, 49100

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, France, 63003

CHU Arnaud de Villeneuve

Montpellier, France, 34295

Germany

Universitaetsklinikum Essen

Essen, Nordrhein Westfalen, Germany, 45122

Charite - Campus Virchow-Klinikum

Berlin, Germany, 13353

Guatemala

Unidad de Cirugía Cardiovascular de Guatemala (UNICAR)

Guatemala, Guatemala

Unidad Nacional de Oncología Pediátrica (UNOP)

Guatemala, Guatemala

Hungary

Semmelweis University 2nd Department of Pediatrics

Budapest, Hungary, 1094

Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases

Budapest, Hungary, H-1097

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

University of Szeged, Department of Pediatrics

Szeged, Hungary, 6720

India

Sir Ganga Ram Hospital

New Delhi, Delhi, India, 110060

Shree Krishna Hospital & Medical Research Centre, H M Patel Centre for Medical Care and Education

Karamsad, Gujarat, India, 388325

Nirmal Hospital

Surat, Gujarat, India, 395002

Jain Institute of Vascular Sciences

Bangalore, Karnataka, India, 560052

M. S. Ramaiah Medical College and Hospital

Bangalore, Karnataka, India, 560054

Government Medical College and Hospital

Nagpur, Maharashtra, India, 440003

Christian Medical College

Ludhiana, Punjab, India, 141008

Institute of Child Health

Kolkata, West Bengal, India, 700017

Indraprastha Apollo Hospitals

Delhi, India, 110076

Israel

Rambam Medical Center

Haifa, Israel, 3109601

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Hadassah ein Kerem

Jerusalem, Israel, 91120

Chaim Sheba Medical Center

Ramat Gan, Israel, 52621

Kenya

Strathmore University Medical Centre

Nairobi, Kenya, 59857-00200

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Seoul National University Hospital

Seoul, Korea, Republic of, 3080

Severance Hospital, Yonsei University

Seoul, Korea, Republic of, 3722

Samsung Medical Center

Seoul, Korea, Republic of, 6351

Lebanon

American University of Beirut Medical Center

Beirut, Lebanon, 1107 2020

Saint George University Hospital Medical Center

Beirut, Lebanon, 166378

Hotel Dieu de France Hospital

Beirut, Lebanon, 166830

Malaysia

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, Malaysia, 15586

Netherlands

Erasmus MC Sophia

Rotterdam, Netherlands, 3000 CB

Norway

Oslo University Hospital

Oslo, Norway, 15-274

Panama

INDICASAT AIP Site 7871

Panamá, Panama, 0843-01103

INDICASAT AIP Site 7872

Panamá, Panama, 0843-01103

Portugal

Hospital de Braga

Braga, Portugal, 4710-243

Hospital da Senhora da Oliveira

Guimarães, Portugal, 4835-044

Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santa Marta

Lisboa, Portugal, 1169-1024

Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisboa, Portugal, 1649-035

Romania

S.C Centrul Clinic Mediquest S.R.L

Sângeorgiu De Mureş, Romania, 547530

Russian Federation

FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion, FMBA"

Kirov, Russian Federation, 610027

Russian Scientific Center of Radiology and Nuclear Medicine of Ministry of Health of Russian Federation, Department of Pediatric Oncology

Moscow, Russian Federation, 117997

Serbia

Mother and Child Health Care Institute of Serbia "Dr. Vukan Cupic"

Belgrade, Serbia, 11070

Clinical Center Kragujevac

Kragujevac, Serbia, 34000

Singapore

National University Hospital

Singapore, Singapore, 119074

KK Women's And Children's Hospital

Singapore, Singapore, 229899

Slovenia

University Medical Centre Ljubljana

Ljubljana, Slovenia, 1000

Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 8035

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario Virgen Macarena

Sevilla, Spain, 41009

Hospital Universitario Araba

Vitoria, Álava, Spain, 01009

Taiwan

Buddhist Tzu Chi General Hospital

Hualien City, Taiwan, 970

Kaohsiung Veterans General Hospital

Kaohsiung, Taiwan, 81362

China Medical University Hospital

Taichung, Taiwan, 40447

Taichung Veterans General Hospital

Taichung, Taiwan, 40705

Taipei Medical University Hospital

Taipei City, Taiwan, 11031

Thailand

Ramathibodi Hospital

Bangkok, Thailand, 10300

King Chulalongkorn Memorial Hospital

Bangkok, Thailand, 10330

Phramongkutklao Hospital

Bangkok, Thailand, 10400

Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University

Chiang Mai, Thailand, 50200

Srinagarind Hospital

Khon Kaen, Thailand, 40002

Songklanagarind Hospital

Songkhla, Thailand, 90110

Turkey

Cukurova University Faculty of Medicine Balcali Hospital Pediatry Department

Adana, Turkey, 1330

Hacettepe University Medical Faculty

Ankara, Turkey, 6100

Ankara Çocuk Sağlığı Ve Hastalıkları Hematoloji Onkoloji Eğitim Araştırma Hastanesi

Ankara, Turkey, 6110

Istanbul University Istanbul Medical Faculty

Istanbul, Turkey, 34093

Yeditepe University Oncology Hospital

Istanbul, Turkey, 34718

Ege University Medical Faculty

Izmir, Turkey, 35040

Izmir Tepecik Training and Research Hospital

Izmir, Turkey, 35170

Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi

Izmir, Turkey, 35210

Erciyes University Medical Faculty

Kayseri, Turkey, 38039

Mersin University Health Research and Practice Hospital

Mersin, Turkey, 33343

Ukraine

Regional Children's Clinical Hospital

Dnipro, Ukraine, 49100

CI of Healthcare Regional Children CH Gastroenterology Center Kharkiv NMU

Kharkiv, Ukraine, 61093

Children City Clinical Hospital

Poltava, Ukraine, 36004

Sponsors and Collaborators

Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] June 8, 2021

More Information

Publications:

Hokusai-VTE Investigators; Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31. Erratum In: N Engl J Med. 2014 Jan 23;370(4):390.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02798471
• Other Study ID Numbers: DU176b-D-U312; 2016-000991-49 ( EudraCT Number ); CTRI/2018/01/011249 ( Registry Identifier: Clinical Trials Registry - India (CTRI) )
• First Posted: June 14, 2016
• Results First Posted: March 6, 2023
• Last Update Posted: March 6, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:

Pediatric; Venous thrombolism; Pulmonary embolism

Additional relevant MeSH terms:

Edoxaban; Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Heparin; Enoxaparin; Warfarin; Fondaparinux; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors