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

NCT ID: NCT02798471

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 290 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-27
• Study Completion Date: 2022-05-24

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.

Conditions

Venous Thromboembolism (VTE); Pulmonary Embolism; Deep Vein Thrombosis (DVT)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

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

Standard of Care

Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule.

Group Type: EXPERIMENTAL

Standard of Care

Intervention Type: DRUG

Standard of care could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors.

Interventions

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

Intervention Type: DRUG

Standard of Care

Standard of care could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors.

Intervention Type: DRUG

Other Intervention Names

Warfarin/heparin; Enoxaparin; Fondaparinux

Eligibility 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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Banner University Medical Center

Tucson, Arizona, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

UCLA Medical Center CAR

Los Angeles, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

University of Louisville

Louisville, Kentucky, United States

Spectrum Health Helen DeVos Children's Hospital Grand Rapids

Grand Rapids, Michigan, United States

Children's Hospital & Clinics of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

University North Carolina- Chapel Hill

Chapel Hill, North Carolina, United States

Levine Children's Hospital Charlotte

Charlotte, North Carolina, United States

The Presbyterian Hospital

Charlotte, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Hasbro Children's Hospital

Providence, Rhode Island, United States

Le Bonheur Childrens Hospital

Memphis, Tennessee, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Hospital Italiano Regional del Sur

Buenos Aires, , Argentina

Sanatorio Allende

Córdoba, , Argentina

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba, Paraná, Brazil

IMIP - Instituto de Medicina Integral Professor Fernando Figueira

Pernambuco, Recife, Brazil

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

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

Hospital de Câncer de Barretos - Fundação Pio XII

Barretos, São Paulo, Brazil

Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP

Campinas, São Paulo, Brazil

Centro Multidisciplinar de Estudos Clínicos - CEMEC

Santo André, São Paulo, Brazil

Santa Casa de Votuporanga

Votuporanga, São Paulo, Brazil

Hospital Samaritano

São Paulo, , Brazil

Hospital da Luz Amico Saude LTDA

São Paulo, , Brazil

Hospital Infantil Pequeno Príncipe

São Paulo, , Brazil

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

São Paulo, , Brazil

UNIFESP - Universidade Federal de São Paulo

São Paulo, , Brazil

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

São Paulo, , Brazil

HMCG - Hospital e Maternidade Dr. Christovão da Gama

São Paulo, , Brazil

UMHAT "Sv. Georgi", EAD

Plovdiv, , Bulgaria

MHAT - "National Heart Hospital" EAD

Sofia, , Bulgaria

MHAT 'Tokuda Hospital Sofia', EAD

Sofia, , Bulgaria

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

Sofia, , Bulgaria

Edmonton Clinic Health Academy

Edmonton, Alberta, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

McMaster Children's Hospital

Hamilton, Ontario, Canada

Hospital El Carmen Dr. Luis Valentin Ferrada

Maipú, , Chile

Clinica Las Condes

Santiago, , Chile

Clinical Hospital Centre Rijeka

Rijeka, , Croatia

General Hospital Zadar

Zadar, , Croatia

Children's Hospital Zagreb

Zagreb, , Croatia

University Hospital Centre Zagreb, University of Zagreb School of Medicine

Zagreb, , Croatia

Fakultni nemocnice Brno

Brno, , Czechia

CTC Hodonin s.r.o.

Hodonín, , Czechia

Dětská klinika Fakultní nemocnice

Hradec Králové, , Czechia

University Hospital Pilsen, CZ

Pilsen, , Czechia

Ålborg Universitetshospital

Aalborg, , Denmark

Hospital Nacional de Niños Benjamín Bloom

San Salvador, Salvador, El Salvador

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

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, , France

CHU Arnaud de Villeneuve

Montpellier, , France

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Charite - Campus Virchow-Klinikum

Berlin, , Germany

Unidad de Cirugía Cardiovascular de Guatemala (UNICAR)

Guatemala City, , Guatemala

Unidad Nacional de Oncología Pediátrica (UNOP)

Guatemala City, , Guatemala

Semmelweis University 2nd Department of Pediatrics

Budapest, , Hungary

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

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

University of Szeged, Department of Pediatrics

Szeged, , Hungary

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

Karamsad, Gujarat, India

Nirmal Hospital

Surat, Gujarat, India

Jain Institute of Vascular Sciences

Bangalore, Karnataka, India

M. S. Ramaiah Medical College and Hospital

Bangalore, Karnataka, India

Government Medical College and Hospital

Nagpur, Maharashtra, India

Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, India

Christian Medical College

Ludhiana, Punjab, India

Institute of Child Health

Kolkata, West Bengal, India

Indraprastha Apollo Hospitals

Delhi, , India

Rambam Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah ein Kerem

Jerusalem, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Strathmore University Medical Centre

Nairobi, , Kenya

American University of Beirut Medical Center

Beirut, , Lebanon

Saint George University Hospital Medical Center

Beirut, , Lebanon

Hotel Dieu de France Hospital

Beirut, , Lebanon

Hospital Raja Perempuan Zainab II

Kota Bharu, Kelantan, Malaysia

Erasmus MC Sophia

Rotterdam, , Netherlands

Oslo University Hospital

Oslo, , Norway

INDICASAT AIP Site 7871

Panama City, , Panama

INDICASAT AIP Site 7872

Panama City, , Panama

Hospital de Braga

Braga, , Portugal

Hospital da Senhora da Oliveira

Guimarães, , Portugal

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

Lisbon, , Portugal

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

Lisbon, , Portugal

S.C Centrul Clinic Mediquest S.R.L

Sângeorgiu de Mureş, , Romania

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

Kirov, , Russia

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

Moscow, , Russia

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

Belgrade, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

National University Hospital

Singapore, , Singapore

KK Women's And Children's Hospital

Singapore, , Singapore

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Araba

Vitoria-Gasteiz, Álava, Spain

Buddhist Tzu Chi General Hospital

Hualien City, , Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

Ramathibodi Hospital

Bangkok, , Thailand

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Phramongkutklao Hospital

Bangkok, , Thailand

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

Chiang Mai, , Thailand

Srinagarind Hospital

Khon Kaen, , Thailand

Songklanagarind Hospital

Songkhla, , Thailand

Cukurova University Faculty of Medicine Balcali Hospital Pediatry Department

Adana, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Ankara Çocuk Sağlığı Ve Hastalıkları Hematoloji Onkoloji Eğitim Araştırma Hastanesi

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Yeditepe University Oncology Hospital

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Izmir Tepecik Training and Research Hospital

Izmir, , Turkey (Türkiye)

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

Izmir, , Turkey (Türkiye)

Erciyes University Medical Faculty

Kayseri, , Turkey (Türkiye)

Mersin University Health Research and Practice Hospital

Mersin, , Turkey (Türkiye)

Regional Children's Clinical Hospital

Dnipro, , Ukraine

CI of Healthcare Regional Children CH Gastroenterology Center Kharkiv NMU

Kharkiv, , Ukraine

Children City Clinical Hospital

Poltava, , Ukraine

Countries

United States; Argentina; Brazil; Bulgaria; Canada; Chile; Croatia; Czechia; Denmark; El Salvador; France; Germany; Guatemala; Hungary; India; Israel; Kenya; Lebanon; Malaysia; Netherlands; Norway; Panama; Portugal; Romania; Russia; Serbia; Singapore; Slovenia; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Ukraine

References

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.

Reference Type: BACKGROUND

PMID: 23991658 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-000991-49

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTRI/2018/01/011249

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCT02798471

Identifier Type: REGISTRY

Identifier Source: secondary_id

DU176b-D-U312

Identifier Type: -

Identifier Source: org_study_id