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Trial record 17 of 656 for:    Russian Federation | Chile

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

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ClinicalTrials.gov Identifier: NCT02798471
Recruitment Status : Recruiting
First Posted : June 14, 2016
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE May 11, 2016
First Posted Date  ICMJE June 14, 2016
Last Update Posted Date February 12, 2019
Actual Study Start Date  ICMJE March 27, 2017
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 8, 2016)
  • Composite and adjudicated endpoint: symptomatic recurrent VTE [ Time Frame: During the First 3-Month Period ]
    Diagnosis of recurrent 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
  • Composite and adjudicated endpoint: death as a result of VTE [ Time Frame: During the First 3-Month Period ]
    Death from VTE is based on objective diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out
  • Composite and adjudicated endpoint: no change or extension of thrombotic burden [ Time Frame: During the First 3-Month Period ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02798471 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2017)
  • Composite and adjudicated endpoints: Major bleeding [ Time Frame: During the First 3-Month Period ]
    Major bleeding is defined as a composite of any of the following: fatal bleeding, clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the central nervous system.
  • Composite and adjudicated endpoints: Clinically relevant non-major bleeding [ Time Frame: During the First 3-Month Period ]
    Defined as either of the following: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition, bleeding that requires medical or surgical or percutaneous intervention to restore hemostasis other than in an operating suite.
  • Composite and adjudicated endpoints of: Symptomatic recurrent VTE, death as a result of VTE and major and clinically relevant non-major bleeding. [ Time Frame: During the First 3-Month Period + 30 Days ]
    Assessments of this outcome is similar to those identified for outcomes 1, 2, 4, 5
  • Pharmacokinetics of Edoxaban: Peak plasma concentration (Cmax) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PK parameter
  • Pharmacokinetics of Edoxaban: Area under the plasma concentration vs. time curve (AUC) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PK parameter
  • Pharmacokinetics of Edoxaban: Apparent systemic clearance (CL/F) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PK parameter
  • Pharmacokinetics of Edoxaban: Apparent volume of distribution (V/F) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PK parameter
  • Pharmacodynamics of Edoxaban: Prothrombin time (PT) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PD parameter
  • Pharmacodynamics of Edoxaban: Activated partial thromboplastin time (aPTT) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PD parameter
  • Pharmacodynamics of Edoxaban: Anti-activated factor X (Anti-FXa) [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PD parameter
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2016)
  • Composite and adjudicated endpoints: Major bleeding [ Time Frame: During the First 3-Month Period ]
    Major bleeding is defined as a composite of any of the following: fatal bleeding, clinically overt bleeding associated with a decrease in hemoglobin of at least 20 g/L in a 24-hour period, bleeding that is retroperitoneal, pulmonary, intracranial, or otherwise involves the central nervous system.
  • Composite and adjudicated endpoints: Clinically relevant non-major bleeding [ Time Frame: During the First 3-Month Period ]
    Defined as either of the following: overt bleeding for which blood product is administered and not directly attributable to the subject's underlying medical condition, bleeding that requires medical or surgical or percutaneous intervention to restore hemostasis other than in an operating suite.
  • Composite and adjudicated endpoints of: Symptomatic recurrent VTE, death as a result of VTE and major and clinically relevant non-major bleeding. [ Time Frame: During the First 3-Month Period + 30 Days ]
    Assessments of this outcome is similar to those identified for outcomes 1, 2, 4, 5
  • Pharmacokinetics of Edoxaban - Cmax [ Time Frame: Treatment Day 5 sparse blood sampling ]
    Peak plasma concerntration
  • Pharmacokinetics of Edoxaban- AUC [ Time Frame: Treatment Day 5 sparse blood sampling ]
    Area under the plasma concerntration vs. time curve
  • Pharmacokinetics of Edoxaban- CL/F [ Time Frame: Treatment Day 5 sparse blood sampling ]
    Apparent systemic clearance
  • Pharmacokinetics of Edoxaban- V/F [ Time Frame: Treatment Day 5 sparse blood sampling ]
    Apparent volume of distribution
  • Pharmacodynamics of Edoxaban - Anticoagulation parameters [ Time Frame: Treatment Day 5 sparse blood sampling ]
    PT, aPTT, anti-FXa.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hokusai Study in Pediatric Patients With Confirmed Venous Thromboembolism (VTE)
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Venous Thromboembolism (VTE)
  • Pulmonary Embolism
  • Deep Vein Thrombosis (DVT)
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Edoxaban
  • Experimental: Standard of Care
    Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule.
    Intervention: Drug: Standard of Care
Publications * Hokusai-VTE Investigators, Büller HR, Décousus 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 8, 2016)
274
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Brazil,   Bulgaria,   Canada,   Croatia,   Czechia,   Denmark,   El Salvador,   France,   Germany,   Guatemala,   Hungary,   India,   Israel,   Kenya,   Korea, Republic of,   Lebanon,   Malaysia,   Netherlands,   Norway,   Panama,   Portugal,   Serbia,   Singapore,   Slovenia,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United States
Removed Location Countries Colombia,   Egypt,   Italy,   Mexico,   Poland,   Romania
 
Administrative Information
NCT Number  ICMJE NCT02798471
Other Study ID Numbers  ICMJE DU176b-D-U312
2016-000991-49 ( EudraCT Number )
CTRI/2018/01/011249 ( Registry Identifier: Clinical Trials Registry - India (CTRI) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP