The primary objective is:- to characterize the pharmacokinetic/pharmacodynamic profile of a 7-day treatment with oral rivaroxabanThe secondary objectives are:- to assess the incidence of major bleeding and clinically relevant non-major bleeding- to…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Results of pharmacokinetics (PK) / pharmacodynamics (PD) (prothrombin time,
activated partial thromboplastin time and anti-factor Xa activity).
Secondary outcome
Composite of major and clinically relevant non-major bleeding. Composite of all
symptomatic recurrent thromboembolism and asymptomatic deterioration in
thrombotic burden on repeat imaging.
Background summary
Treatment with heparins and VKA has several unsatisfying aspects. For heparins,
these include the requirement for intravenous or subcutaneous injection and
monitoring of the activated partial thromboplastin time (aPTT). For VKA, these
include a slow onset and offset of action, a narrow therapeutic window
requiring frequent INR 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 not only for adults, but especially for the
pediatric population.
Study objective
The primary objective is:
- to characterize the pharmacokinetic/pharmacodynamic profile of a 7-day
treatment with oral rivaroxaban
The secondary objectives are:
- to assess the incidence of major bleeding and clinically relevant non-major
bleeding
- to assess the incidence of symptomatic recurrent thromboembolism and
- to assess asymptomatic deterioration in the thrombotic burden on repeat
imaging
Study design
This is a non-randomized, open label, multicenter study evaluating the safety,
efficacy and PK/PD profile of a 7-day treatment with age- and body
weight-adjusted oral rivaroxaban in neonates and infants younger than 6 months
with symptomatic or asymptomatic arterial or venous thrombosis.
Intervention
Age- and body weight-adjusted three times daily dosing of rivaroxaban (oral
suspension) during 7 days.
Study burden and risks
The study includes 5 planned visits. In total 5 PK/PD blood samples will be
taken and the total blood volume taken will be 6.6 ml. Additionally, two
regular blood samples will be taken during visit 1 and 4 (if not available from
standard care). General physical exam will be performed during each visit.
There is a chance for (unknown) side effects, as is documented in the SmPC's of
rivaroxaban.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
1. Children from birth to less than 6 months with documented symptomatic or asymptomatic venous or arterial thrombosis who have been treated with anticoagulant therapy for at least 5 days.
2. Gestational age at birth of at least 37 weeks.
3. Hemoglobin, platelets, creatinine, ALT and total and direct bilirubin assessed within
10 days prior to enrollment.
4. Oral feeding/nasogastric/gastric feeding for at least 10 days.
5. Informed consent provided.
6. Body weight >2600 g.
Exclusion criteria
1. Active bleeding or high risk for bleeding contraindicating anticoagulant therapy, including history of intra-ventricular bleeding.
2. Symptomatic progression of thrombosis during preceding anticoagulant treatment.
3. Planned invasive procedures, including lumbar puncture and removal of nonperipherally placed central lines during study treatment.
4. 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
5. Creatinine > 1.5 times of normal.
6. Uncontrolled hypertension defined as > 95th percentile.
7. History of gastrointestinal disease or surgery associated with impaired absorption.
8. Platelet count <100 x 109/L.
9. Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), e.g. all human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically (fluconazole is allowed).
10. Concomitant use of strong inducers of CYP3A4, e.g. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine.
11. Indication for anticoagulant therapy other than current thrombosis.
12. An indication for continued antiplatelet therapy or non-steroid anti-inflammatory drug (NSAID) therapy. Incidental use is allowed.
13. Hypersensitivity to rivaroxaban or its excipients.
14. Participation in a study with an investigational drug or medical device within 30 days prior to enrollment.
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 | EUCTR2014-002385-74-NL |
| CCMO | NL52130.078.15 |