venous thromboembolism

To assess the safety of dabigatran etexilate for secondary prevention of venous thromboembolism

Pradaxa Capsules

Dabigatran etexilate

capsule

50.75.110.150/20.30.40.50.110.150/6.25

Primary endpoints:
 Recurrence of venous thromboembolism (VTE) at 6 and 12 months
 Major and minor (including clinically relevant non-major (CRNM)) bleeding
events at 6 and 12 months
 Mortality overall and related to thrombotic or thromboembolic events at 6
and 12 months
Secondary endpoints:
 Occurrence of post-thrombotic syndrome (PTS) at 6 and 12 months
 Pharmacodynamic assessments (central measurement of aPTT and ECT) at
Visit 4
 Number of dabigatran etexilate dose adjustments during treatment period
Other safety assessments:
 Incidence of adverse events, protocol-specified AESI and serious adverse
events
 Treatment discontinuation due to an adverse event
 Change from baseline in safety laboratory values, vital signs and physical
examination
 Global assessment of tolerability (measured as treatment discontinuation and
adherence) to study medication

Inclusion criteria
1. Male or female subjects from 0 to less than 18 years of age at the time of informed
consent / assent and body weight ≤ 40kg.
2. Previously documented objective diagnosis of VTE, followed by completed course of
initial VTE treatment (for at least 3 months) or completed study treatment (i.e.
reached Visit 8) in the 1160.106 trial, up until Visit 1 of this trial.
3. Presence of an unresolved clinical risk factor requiring further anticoagulation for
secondary VTE prevention (e.g. central venous line, underlying disease,
thrombophilia, etc.)
4. Written informed consent provided by the patient’s parent or legal guardian and
assent provided by the patient (if applicable) at the time of ICF signature according to
local regulations.

Exclusion criteria
1. Conditions associated with an increased risk of bleeding:
a. Any prior intracranial haemorrhage
b. Intracranial or intraspinal surgeries within 6 months of Visit 2 or any other major
surgery within 4 weeks of Visit 2. Major surgeries may include an invasive
operation upon an organ within the cranium, chest, abdomen, pelvic cavity or any
other procedure regarded as major surgery per investigator judgment. In general,
major surgery involves the opening of a mesenchymal barrier (pleural cavity,
peritoneum, meninges). Removal of a central venous line is not considered a
major surgery
c. Any major planned procedure that might put the patient at an increased risk of a
bleed per investigator judgement within 5 days prior to taking study medication
d. History of intraocular, spinal, retroperitoneal or atraumatic intra-articular
bleeding unless the causative factor has been permanently treated (e.g. by
surgery)
e. Gastrointestinal haemorrhage within the past year prior to screening unless the
cause has been permanently eliminated (e.g., by surgery)
f. History of gastroduodenal ulcer disease
g. History of haemorrhagic disorder or bleeding diathesis (e.g. von Willebrand
disease, haemophilia A or B or other hereditary bleeding disorder, history of
spontaneous intra-articular bleeding, history of prolonged bleeding after surgery /
intervention)
h. Administration of a fibrinolytic agents within 48 hours of dabigatran etexilate
administration (Please note the following exception: use of tissue plasminogen
activator (t-PA) e.g. alteplase, or any other thrombolytic agents to re-establish
patency of an obstructed central venous line are allowed as long as the used dose
is devoid of relevant systemic effects)
i. Uncontrolled hypertension on antihypertensive medication (systolic and / or
diastolic above the upper limit of normal for age and sustained over 24 hours)
j. Any other disease, health condition or intervention which in the investigator’s
opinion exposes the patient to a higher risk for bleeding
2. Renal dysfunction (eGFR < 80 mL/min/1.73m2
using the Schwartz formula, refer to
Appendix 10.1) or requirement for dialysis
3. Active infective endocarditis
4. Subjects with a mechanical or a biological heart valve prosthesis
5. Hepatic disease:
a. Active liver disease, including known hepatitis A, B or C or,
b. Persistent alanine aminotransferase (ALT) or aspartate transaminase (AST) or
alkaline phosphatase (AP) > 2 × upper limit of normal (ULN) within 3 months of
screening
6. Pregnant or breast feeding females. Females who have reached menarche and are not
using an acceptable method of birth control, or do not plan to continue using this
method throughout the study and / or do not agree to adhere to pregnancy testing
required by this protocol . Acceptable methods of birth control are listed below and
must be used in a correct and consistent manner:
i. Oral or parenteral (patch, injection, implant) hormonal contraception
which has been used continuously for at least one (1) month prior to the
first dose of study medication
ii. Intrauterine device (IUD) or intrauterine system (IUS)
iii. Double-Barrier method of contraception: condom and spermicidal agent
iv. Complete sexual abstinence. Note: Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
7. Anaemia (haemoglobin < 80g/L) or thrombocytopenia (platelet count < 80 x 109
/L) at
screening. Transfusions during the screening period are allowed, provided that a
satisfactory haemoglobin or platelet level is attained prior to Visit 2
8. Patients who have taken restricted medication prior to first dose of study medication.
For trial restrictions please see Section 4.2.2
9. Patients who have received an investigational drug in the past 30 days prior to
screening, except patients who have completed the treatment period (up to Visit 8) in
1160.106 trial
10. Patients who are allergic / sensitive to any component of the study medication
including solvent
11. 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