The primary efficacy objective is to assess the incidence of symptomatic recurrent venous thromboembolism.The secondary efficacy objective is to assess the incidence of symptomatic recurrent venous thromboembolism and asymptomatic deterioration on…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Assessment of incidence of symptomatic recurrent venous thromboembolism.
Secondary outcome
- Assessment of all symptomatic recurrent venous thromboembolism and
asymptomatic deterioration on repeat imaging
- Assessment of the incidence of over major and clinically relevant non major
bleeding
- Characterize the pharmacokinetic/pharmacodynamics profile of rivaroxaban
Background summary
Treatment with heparins and VKA (vitamin K antagonist) has several unsatisfying
aspects. For heparins, this includes the requirement for intravenous or
subcutaneous injection and monitoring of the activated partial thromboplastin
time (aPTT). For VKA, this includes a slow onset and offset of action, a narrow
therapeutic window requiring frequent INR (international normalized ratio)
monitoring, and subsequent dose adjustments, caused by food and drug
interactions. An oral anticoagulant drug that requires no monitoring of its
effect, with a rapid onset of action and a high benefit-risk ratio is of
considerable interest for the pediatric population.
Study objective
The primary efficacy objective is to assess the incidence of symptomatic
recurrent venous thromboembolism.
The secondary efficacy objective is to assess the incidence of symptomatic
recurrent venous thromboembolism and asymptomatic deterioration on repeat
imaging.
The principal safety objective is to assess the incidence of overt major and
clinically relevant non major bleeding.
An additional objective is to characterize the pharmacokinetic /
pharmacodynamics profile of rivaroxaban.
Study design
This is a multicenter, open-label, active-controlled, randomized study to
evaluate the efficacy and safety of an age- and body weight-adjusted
rivaroxaban regimen in children with acute venous thromboembolism.
Intervention
Randomization into three arms:
1. Rivaroxaban (suspension) once, twice or three times daily (depending on body
weight) for at least 3 months up to maximum 12 months (for children aged < 2
years with catheter related thrombosis: at least one month up to maximum of
three months).
2. Standard treatment in the Netherlands, consisting of VKA (tablets) or LMWH
(injections) for 3 months up to a maximum of 12 months
Children aged 0 months - 6 years will be given the rivaroxaban suspension,
children aged 6 - 12 years will be given the choice between rivaroxaban tablets
or suspension, children aged 12 - 18 years will be given the rivaroxaban
tablets.
Protocol V3.0: all children will receive the rivaroxaban suspension; tablets
are no longer used (sufficient data collected).
Protocol V4.0: all children will receive the rivaroxaban suspension; tablets
are no longer used (sufficient data collected).
Protocol V5.0: all children will receive the rivaroxaban suspension; tablets
are no longer used (sufficient data collected).
Study burden and risks
The study has 5 to 8 planned visits, depending on the elected study duration.
Patients randomized to the rivaroxaban-arm, who receive a three times daily
dose, will have an additional visit (visit 1A).
At the end of the initial 3 month treatment period, the decision is made to
stop study treatment or to continue for an additional 3 months (for children
aged < 2 years with catheter related thrombosis this will be decided after 1
month). The need to continue with anticoagulant treatment will be assessed
every 3 months (for children aged < 2 years with catheter related thrombosis
every month) for up to 9 additional months (up to 3 months for children aged <
2 years with catheter related thrombosis).
Regardless of the duration of study treatment (3, 6, 9 or 12 months), an
additional 1-month post-treatment observational period will be completed for
all children. If the child is treated with rivaroxaban, 4 blood samples
(children 12 kg and above 12 kg) or 6 blood samples (children below 12 kg) will
be taken for PK/PD evaluation and if the child is treated with VKA, at least 1
blood sample will be taken every 2 weeks for monitoring anticoagulant
treatment.
Diagnostic imaging test will be obtained at baseline and if clinically feasible
will be repeated at the end of the initial 3 month treatment period (after one
month for children aged < 2 years with catheter related thrombosis).
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
1. - Children aged birth to < 18 years with confirmed venous thromboembolism who receive initial treatment with therapeutic dosages of UFH, LMWH or fondaparinux and require anticoagulant therapy for at least 90 days. However, children aged birth to < 2 years with catheter-related thrombosis require anticoagulant therapy for at least 30 days.
For children younger than 6 months:
- Gestational age at birth of at least 37 weeks.
- Oral feeding/nasogastric/gastric feeding for at least 10 days.
- Body weight *2600 g ;2. Informed consent provided and, if applicable, child assent provided
Exclusion criteria
1. Active bleeding or bleeding risk contraindicating anticoagulant therapy;2. An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 ;3. Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase (ALT) > 5x upper level of normal (ULN) or total bilirubin (TB) > 2x ULN with direct bilirubin > 20% of the total;4. Platelet count < 50 x 109/L;5. Sustained uncontrolled hypertension defined as systolic and/or diastolic blood pressure > 95th age percentile;6. Life expectancy < 3 months;7. Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), including but not limited to all human immunodeficiency virus protease
inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically ;8. Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine;9. Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000565-47-NL |
| CCMO | NL49368.078.14 |