Hokusai Study in Pediatric Patients With Confirmed Venous Thromboembolism (VTE)
Condition: Venous Thromboembolism (VTE); Pulmonary Embolism; Deep Vein Thrombosis (DVT)
MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis
Intervention: Edoxaban; Standard of Care
Intervention description: 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 could include low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors.
Intervention MeSH terms: Heparin; Enoxaparin; Warfarin; Edoxaban; Fondaparinux
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 290.0
Sex: All
Minimum age: 1 Day
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatric; Venous thrombolism; Pulmonary embolism

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.
    

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.