Open Label Study Comparing Efficacy and Safety of Dabigatran Etexilate to Standard of Care in Paediatric Patients With Venous Thromboembolism (VTE)
Condition: Venous Thromboembolism
MeSH terms: Thromboembolism; Venous Thromboembolism
Intervention: dabigatran etexilate; standard of care
Intervention description: Age and weight appropriate capsule dose (combination of 50 mg, 75 mg and 110 mg capsules) or pellets or oral liquid formulation; Low molecular weight heparin, vitamin K antagonist or fondaparinux prescribed in an open label fashion for 3 months (these medications will not supplied in this study as IMP)
Intervention MeSH terms: Dabigatran
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 267.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The main objectives of this large phase IIb/III paediatric study are to assess the efficacy
      and safety of dabigatran etexilate relative to standard of care and to document the
      appropriateness of the proposed dabigatran etexilate dosing algorithm for use in patients
      from birth to less than 18 years of age.
    

Eligibility criteria:

        Inclusion criteria:

          -  Male or female subjects 0 to less than 18 years of age at the time of informed consent
             / assent

          -  Documented diagnosis of clinically stable VTE (e.g. DVT, PE, central line thrombosis,
             sinus vein thrombosis) per investigator judgment, initially treated (minimum of 5 to 7
             days, but not longer than 21 days) with parenteral anticoagulation therapy, such as
             unfractionated heparin (UFH) or a low molecular weight heparin (LMWH).

          -  Clinical indication for at least 3 month of treatment with anticoagulants for the VTE
             episode defined under the above inclusion criterion.

          -  Written informed consent provided by the patient's parent or legal guardian and assent
             provided by the patient (if applicable) at the time of informed consent form (ICF)
             signature according to local regulations.

        Exclusion criteria:

          -  Conditions associated with an increased risk of bleeding

          -  Renal dysfunction (eGFR < 50 mL/min/1.73m^2 using the Schwartz formula) or requirement
             for dialysis. eGFR retesting during the screening period is allowed (once).

          -  Active infective endocarditis

          -  Subjects with a heart valve prosthesis requiring anticoagulation.

          -  Hepatic disease:

        Active liver disease, including known active hepatitis A, B or C or, Persistent alanine
        aminotransferase (ALT) or aspartate transaminase (AST) or alkaline phosphatase (AP) > 3 ×
        upper limit of normal (ULN) within 3 months of screening

          -  Pregnant or breast feeding females. Females who have reached menarche and are not
             using a medically accepted contraceptive method per local guidelines. Acceptable
             methods of birth control must be used in a correct and consistent manner

          -  Patients in stratum 3 (0 to < 2 years) with gestational age at birth < 37 weeks or
             with body weight lower than the 3rd percentile

          -  Anemia (hemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109/L) at
             screening. Transfusions during the screening period are allowed, provided that a
             satisfactory hemoglobin or platelet level is attained prior to visit 2

          -  Patients who have taken prohibited or restricted medication within one week of the
             first dose of study medication other than medication for prior VTE treatment and
             P-glycoprotein inhibitors..

          -  Patients who have received an investigational drug in the past 30 days prior to
             screening

          -  Patients who are allergic/sensitive to any component of the study medication including
             solvent

          -  Patients or parents/legal guardians considered unreliable to participate in the trial
             per investigator judgment or any condition which would present a safety hazard to the
             patient based on investigator judgment

          -  Patients or parents/legal guardians who are unwilling or unable to undergo or permit
             repeat of the baseline imaging tests required to confirm thrombus resolution at study
             day 84 (or eEOT, whichever comes first) or in whom repeating such imaging tests at
             these pre-specified time points may not be medically in the patient's best interest.
             Examples may include unwarranted radiation exposure as a result of a repeat CT scan at
             day 84 for a patient with an isolated case of pulmonary embolism evaluated at baseline
             solely by a CT scan. In such cases, the baseline radiological assessment (e.g. CT) may
             be supplemented with an acceptable non-radiological assessment at baseline (e.g. MRI)
             which could then be repeated at day 84 hence alleviating any potential unwarranted
             radiation exposure.

          -  Further exclusion criteria apply