Rivaroxaban for treatment in venous thrombosis in children

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-000565-47-AT
• Date of registration: 23/06/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Rivaroxaban for treatment in venous thrombosis in children
• Scientific title: Multicenter, open-label, active-controlled, randomized study to evaluate the efficacy and safety of an age-and body weight-adjusted rivaroxaban regimen compared to standard of care in children with acute venous thromboembolism - EINSTEIN Junior Phase III: oral rivaroxaban in young children with venous thrombosis
• Date of first enrolment: 25/07/2014
• Target sample size: 170
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000565-47
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Finland, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Children aged 6 months 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.
2. Informed consent provided and, if applicable, child assent provided
3. 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 170
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Active bleeding or bleeding risk contraindicating anticoagulant therapy
2. An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (in children younger than 1 year, serum creatinine results above 97.5th percentile excludes participation)
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 (fluconazole is allowed). For exceptions, see Section 4.4 of the Study Protocol.
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
10. Hypersensitivity or any other contraindication listed in the local labeling for the comparator treatment or experimental treatment
11. Inability to cooperate with the study procedures
12. Participation in a study with an investigational drug or medical device within 30 days prior to randomization


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Venous Thrombosis
MedDRA version: 20.0 Level: LLT Classification code 10066899 Term: Venous thromboembolism System Organ Class: 100000004866

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Xarelto
Product Code: BAY59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Xarelto
Product Code: BAY59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-

Trade Name: Xarelto 10 mg
Product Name: Xarelto
Product Code: BAY59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Xarelto 15 mg
Product Name: Xarelto
Product Code: BAY59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-7939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Xarelto 20 mg
Product Name: Xarelto
Product Code: BAY59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIVAROXABAN
CAS Number: 366789-02-8

Primary Outcome(s)

Main Objective: The primary efficacy objective is: To assess the incidence of symptomatic recurrent venous thromboembolism

The principal safety objective is: ? To assess the incidence of overt major and clinically relevant non-major bleeding.

Primary end point(s): 1. Efficacy: The composite of all symptomatic recurrent venous thromboembolism

2. Safety: The composite of overt major and clinically relevant non-major bleeding.

Timepoint(s) of evaluation of this end point: 1. At the end of the main study treatment period: After 90 days of treatment and again at 30 days post Treatment (for children below 2 years + catheter related thrombosis: after 30 days of treatment and again at 30 days post Treatment)

2. At the end of main study treatment period: After 90 days of treatment and again at 30 days post Treatment (for children below 2 years + catheter related thrombosis: after 30 days of Treatment and again at 30 days post treatment)

Secondary Objective: The secondary efficacy objective is: To assess the incidence of symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging.
An additional objective is: To characterize the pharmacokinetic / pharmacodynamics profile of rivaroxaban.

Secondary Outcome(s)

Secondary end point(s): 1. The composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging.

2. Results of pharmacokinetics (PK)/ pharmacodynamics (PD) analyses

Timepoint(s) of evaluation of this end point: 1. After the end of main study Treatment period: After 90 days of treatment and again at 30 days post Treatment (for children below 2 years + catheter related thrombosis: after 30 days of treatment and again at 30 days post treatment)

2. PK and PD as defined in the protocol

Secondary ID(s)

BAY59-7939/14372

2014-000565-47-ES

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 14/08/2019
• Date Completed: 30/01/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000565-47/results