Venous Thromboembolism (VTE)Phase 3NCT02798471
Hokusai Study in Pediatric Patients With Confirmed Venous Thromboembolism (VTE)
A Phase 3 study testing Edoxaban in people with Venous Thromboembolism (VTE) and Pulmonary Embolism, run by Daiichi Sankyo at 140 sites in 34 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 day to 17 years
- Conditions the study is for
- Venous Thromboembolism (VTE), Pulmonary Embolism, Deep Vein Thrombosis (DVT)
- What is being tested?
- Edoxaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 290 participants
- Where
- 140 sitesin 34 countries
- Study dates
- 27 Mar 2017to 24 May 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
140 sites in 34 countries.
140 sites in 34 countries
United States22 sites
University North Carolina- Chapel Hill
Chapel Hill, North Carolina, 27517
Levine Children's Hospital Charlotte
Charlotte, North Carolina, 28204
The Presbyterian Hospital
Charlotte, North Carolina, 28210
Rush University Medical Center
Chicago, Illinois, 60612
Spectrum Health Helen DeVos Children's Hospital Grand Rapids
Grand Rapids, Michigan, 49503
East Carolina University
Greenville, North Carolina, 27858
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
Children's Hospital Los Angeles
Los Angeles, California, 90027
UCLA Medical Center CAR
Los Angeles, California, 90095
University of Louisville
Louisville, Kentucky, 40202
Le Bonheur Childrens Hospital
Memphis, Tennessee, 38105
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami Miller School of Medicine
Miami, Florida, 33136
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Hasbro Children's Hospital
Providence, Rhode Island, 02903
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305
University of South Florida
Tampa, Florida, 33606
Banner University Medical Center
Tucson, Arizona, 85724
Brazil16 sites
Hospital de Câncer de Barretos - Fundação Pio XII
Barretos, São Paulo, 14784-400
Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP
Campinas, São Paulo, 13083-878
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Paraná, 81520-060
Hospital São Vicente de Paulo
Passo Fundo, Rio Grande do Sul, 99010-080
Hospital da Cidade de Passo Fundo
Passo Fundo, Rio Grande do Sul, 99010-260
IMIP - Instituto de Medicina Integral Professor Fernando Figueira
Pernambuco, Recife, 50070-550
Instituto de Cardiologia do Rio Grande do Sul
Pôrto Alegre, Rio Grande do Sul, 90620-001
Centro Multidisciplinar de Estudos Clínicos - CEMEC
Santo André, São Paulo, 09190-510
Hospital Samaritano
São Paulo, 01232-010
Hospital da Luz Amico Saude LTDA
São Paulo, 04013-060
Hospital Infantil Pequeno Príncipe
São Paulo, 04013-060
GRAACC - Grupo de Apoio ao Adolescente e à Criança com Câncer
São Paulo, 04039-001
UNIFESP - Universidade Federal de São Paulo
São Paulo, 04039-032
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, 05403-000
HMCG - Hospital e Maternidade Dr. Christovão da Gama
São Paulo, 09030-010
Santa Casa de Votuporanga
Votuporanga, São Paulo, 15500-003
Turkey (Türkiye)10 sites
Cukurova University Faculty of Medicine Balcali Hospital Pediatry Department
Adana, 1330
Hacettepe University Medical Faculty
Ankara, 6100
Ankara Çocuk Sağlığı Ve Hastalıkları Hematoloji Onkoloji Eğitim Araştırma Hastanesi
Ankara, 6110
Istanbul University Istanbul Medical Faculty
Istanbul, 34093
Yeditepe University Oncology Hospital
Istanbul, 34718
Ege University Medical Faculty
Izmir, 35040
Izmir Tepecik Training and Research Hospital
Izmir, 35170
Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
Izmir, 35210
Erciyes University Medical Faculty
Kayseri, 38039
Mersin University Health Research and Practice Hospital
Mersin, 33343
India9 sites
Jain Institute of Vascular Sciences
Bangalore, Karnataka, 560052
M. S. Ramaiah Medical College and Hospital
Bangalore, Karnataka, 560054
Indraprastha Apollo Hospitals
Delhi, 110076
Shree Krishna Hospital & Medical Research Centre, H M Patel Centre for Medical Care and Education
Karamsad, Gujarat, 388325
Institute of Child Health
Kolkata, West Bengal, 700017
Christian Medical College
Ludhiana, Punjab, 141008
Government Medical College and Hospital
Nagpur, Maharashtra, 440003
Sir Ganga Ram Hospital
New Delhi, National Capital Territory of Delhi, 110060
Nirmal Hospital
Surat, Gujarat, 395002
France7 sites
CHU Angers - Hôpital Hôtel Dieu
Angers, 49100
Clinical Hospital Centre Cavale Blanche BREST
Brest, Finistere, 29200
CHU Clermont Ferrand - Hôpital d'Estaing
Clermont-Ferrand, 63003
CHU Arnaud de Villeneuve
Montpellier, 34295
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
Pessac, Gironde, 33600
CHU Rennes - Hopital Sud
Rennes, Ille Et Vilaine, 35203
Hôpital des enfants, CHU Toulouse
Toulouse, Haute Garonne, 31059
Thailand6 sites
Ramathibodi Hospital
Bangkok, 10300
King Chulalongkorn Memorial Hospital
Bangkok, 10330
Phramongkutklao Hospital
Bangkok, 10400
Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University
Chiang Mai, 50200
Srinagarind Hospital
Khon Kaen, 40002
Songklanagarind Hospital
Songkhla, 90110
Taiwan5 sites
Buddhist Tzu Chi General Hospital
Hualien City, 970
Kaohsiung Veterans General Hospital
Kaohsiung City, 81362
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
Taipei Medical University Hospital
Taipei, 11031
Bulgaria4 sites
UMHAT "Sv. Georgi", EAD
Plovdiv, 4000
MHAT - "National Heart Hospital" EAD
Sofia, 1309
MHAT 'Tokuda Hospital Sofia', EAD
Sofia, 1407
Medical Center for Specialized Ambulatory Medical Assistance for Children's Diseases
Sofia, 1612
Croatia4 sites
Clinical Hospital Centre Rijeka
Rijeka, 51000
General Hospital Zadar
Zadar, 23000
Children's Hospital Zagreb
Zagreb, 10 000
University Hospital Centre Zagreb, University of Zagreb School of Medicine
Zagreb, 10000
Czechia4 sites
Fakultni nemocnice Brno
Brno, 613 00
CTC Hodonin s.r.o.
Hodonín, 69501
Dětská klinika Fakultní nemocnice
Hradec Králové, 500 05
University Hospital Pilsen, CZ
Pilsen, 305 99
Hungary4 sites
Semmelweis University 2nd Department of Pediatrics
Budapest, 1094
Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases
Budapest, H-1097
Debreceni Egyetem Klinikai Kozpont
Debrecen, 4032
University of Szeged, Department of Pediatrics
Szeged, 6720
Israel4 sites
Rambam Medical Center
Haifa, 3109601
Shaare Zedek Medical Center
Jerusalem, 9103102
Hadassah ein Kerem
Jerusalem, 91120
Chaim Sheba Medical Center
Ramat Gan, 52621
Portugal4 sites
Hospital de Braga
Braga, 4710-243
Hospital da Senhora da Oliveira
Guimarães, 4835-044
Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santa Marta
Lisbon, 1169-1024
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035
South Korea4 sites
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, 3080
Severance Hospital, Yonsei University
Seoul, 3722
Samsung Medical Center
Seoul, 6351
Spain4 sites
Hospital Universitari Vall d'Hebron
Barcelona, 8035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Araba
Vitoria-Gasteiz, Álava, 01009
Canada3 sites
Edmonton Clinic Health Academy
Edmonton, Alberta, T6G 2B7
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Lebanon3 sites
American University of Beirut Medical Center
Beirut, 1107 2020
Saint George University Hospital Medical Center
Beirut, 166378
Hotel Dieu de France Hospital
Beirut, 166830
Ukraine3 sites
Regional Children's Clinical Hospital
Dnipro, 49100
CI of Healthcare Regional Children CH Gastroenterology Center Kharkiv NMU
Kharkiv, 61093
Children City Clinical Hospital
Poltava, 36004
Argentina2 sites
Hospital Italiano Regional del Sur
Buenos Aires, B8001HXM
Sanatorio Allende
Córdoba, X5000JHQ
Chile2 sites
Hospital El Carmen Dr. Luis Valentin Ferrada
Maipú, 9251521
Clinica Las Condes
Santiago, 7591047
Germany2 sites
Charite - Campus Virchow-Klinikum
Berlin, 13353
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45122
Guatemala2 sites
Unidad de Cirugía Cardiovascular de Guatemala (UNICAR)
Guatemala City
Unidad Nacional de Oncología Pediátrica (UNOP)
Guatemala City
Panama2 sites
INDICASAT AIP Site 7871
Panama City, 0843-01103
INDICASAT AIP Site 7872
Panama City, 0843-01103
Russia2 sites
FSBI of Science "Kirov Scientific and Research Institute of Hematology and Blood Transfusion, FMBA"
Kirov, 610027
Russian Scientific Center of Radiology and Nuclear Medicine of Ministry of Health of Russian Federation, Department of Pediatric Oncology
Moscow, 117997
Serbia2 sites
Mother and Child Health Care Institute of Serbia "Dr. Vukan Cupic"
Belgrade, 11070
Clinical Center Kragujevac
Kragujevac, 34000
Singapore2 sites
National University Hospital
Singapore, 119074
KK Women's And Children's Hospital
Singapore, 229899
El Salvador1 site
Hospital Nacional de Niños Benjamín Bloom
San Salvador, Salvador
About this study
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)
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.
Read the 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.
- Being tested
- Edoxaban, Standard of Care
- Keywords
- Pediatric, Venous thrombolism, Pulmonary embolism
- Medical subject headings
- Venous Thromboembolism, Pulmonary Embolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EdoxabanDrug
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 CareDrug
Also called Warfarin/heparin, Enoxaparin, Fondaparinux
Standard of care could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors.
| Study group | Role | What they receive |
|---|---|---|
| Edoxaban | Experimental | 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. Receives: Drug: Edoxaban |
| Standard of Care | Experimental | Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule. Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
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.
Measured: Randomization to Month 3
Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
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.
Measured: Randomization to Month 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)
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).
Measured: Randomization to Month 3
Secondary outcomes (11)
Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
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.
Measured: From randomization up to Month 12
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)
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.
Measured: Randomization to Month 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)
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.
Measured: From randomization up to Month 12
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)
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.
Measured: Randomization to Month 3
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)
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).
Measured: From randomization up to Month 12
Number of Participants With Adjudicated Individual Component of Primary Efficacy Endpoints During the Main Treatment Period Following Edoxaban or Standard of Care Treatment
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).
Measured: Randomization to Month 3
Number of Participants Reporting Adjudicated All-Cause Mortality During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated)
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.
Measured: From randomization up to Month 12
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
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.
Measured: From randomization up to Month 12
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)
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).
Measured: Randomization to Month 3
Number of Participants With All Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
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.
Measured: From randomization up to Month 12
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)
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).
Measured: From randomization up to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study start27 Mar 2017
- Primary completion24 May 2022
- Study completion24 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous Thromboembolism (VTE)Studies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02798471
- Sponsor's protocol ID
- DU176b-D-U312
- Other IDs
- 2016-000991-49, CTRI/2018/01/011249, NCT02798471, 2016
- Status last verified
- Feb 2025
- First submitted
- 11 May 2016
- Last updated
- 28 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
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.
PubMed 23991658
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02798471
- Acronym / sponsor ID
- DU176b-D-U312
- Keywords
- Pediatric, Venous thrombolism, Pulmonary embolism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 290 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2017 (actual)
- Primary completion
- 24 May 2022 (actual)
- Study completion
- 24 May 2022 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 6 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Edoxaban | Experimental | Drug: EdoxabanEdoxaban 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. |
| Standard of Care | Experimental | Drug: Standard of CareStandard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule. |
Who may qualify
- Ages
- 1 day to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Edoxaban15 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 | Drug | Edoxaban |
| Standard of CareAlso: Warfarin/heparin, Enoxaparin, FondaparinuxStandard of care could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors. | Drug | Standard of Care |
Primary outcome
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.
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.
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).
11 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23991658Hokusai-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.
- Related InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
140 sites in 34 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Edoxaban in people with Venous Thromboembolism (VTE) and Pulmonary Embolism, run by Daiichi Sankyo at 140 sites in 34 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 140 sites in United States, Brazil, Turkey (Türkiye), India, France and 29 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02798471, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.