Oral direct factor Xa inhibitor rivaroxaban in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism.

• Register: EUCTR
• Last refreshed on: 28 August 2012
• Main ID: EUCTR2006-004495-13-HU
• Date of registration: 03/04/2007
• Prospective Registration: Yes
• Primary sponsor: Bayer Healthcare AG
• Public title: Oral direct factor Xa inhibitor rivaroxaban in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism.
• Scientific title: Oral direct factor Xa inhibitor rivaroxaban in patients with acute symptomatic deep-vein thrombosis or pulmonary embolism.
• Date of first enrolment: 17/05/2007
• Target sample size: 7400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004495-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
For Einstein-DVT:
confirmed acute symptomatic proximal DVT without symptomatic PE , or
For Einstein-PE:
confirmed acute symptomatic PE with or without symptomatic DVT

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Legal lower age limitations (country specific)
2. Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE
3. Other indication for VKA than DVT and/or PE
4. More than 48 hours pre-randomization treatment with therapeutic dosages of anti-coagulant treatment or more than a single dose of VKA prior to randomization.
5. Participation in another pharmacotherapeutic study within 30 days
6. Creatinine clearance < 30 ml/min,
7. Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT > 3 x ULN
8. Bacterial endocarditis
9. Life expectancy <3 months
10. Active bleeding or high risk for bleeding contraindicating treatment with
enoxaparin or VKA
11. Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
12. Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
13. Any other contraindication listed in the local labeling of warfarin,
acenocoumarol, or enoxaparin
14. Concomitant use of strong CYP3A4 inhibitors (e.g., HIV protease inhibitors, systemic ketokonazole) or strong CYP 3A4 inducers like rifampicin


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

Health Condition(s) or Problem(s) studied

Treatment and secondary prevention of venous thromboembolism in patients with acute symptomatic deep- vein thrombosis or pulmonary embolism

Intervention(s)

Product Name: rivaroxaban
Product Code: BAY 59-7939
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

Product Name: rivaroxaban
Product Code: BAY 59-7939
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

Product Name: warfarin
Pharmaceutical Form: Tablet
INN or Proposed INN: warfarin
Concentration unit: mg milligram(s)
Concentration type: equal

Product Name: enoxaparin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: enoxaparin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal

Product Code: acenocoumarol
Pharmaceutical Form: Tablet
INN or Proposed INN: acenocoumarol
Concentration unit: mg milligram(s)
Concentration type: equal

Primary Outcome(s)

Primary end point(s): The primary efficacy outcome is symptomatic recurrent VTE, i.e., the composite of recurrent DVT or fatal or non-fatal PE occurring during the 3-, 6,- and 12-month study treatment periods.
The following definitions are applied by the CIAC to confirm a suspected episode of symptomatic recurrent PE/DVT. (3;4)
1. Suspected (recurrent) PE with one of the following findings
• a (new) intraluminal filling defect in segmental or more proximal branches on spiral CT scan
• a (new) intraluminal filling defect or an extension of an existing defect or a new sudden cutoff of vessels more than 2.5 mm in diameter on the pulmonary angiogram
• a (new) perfusion defect of at least 75% of a segment with a local normal
ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
• inconclusive sCT, pulmonary angiography or VPLS with demonstration of DVT in the lower extremities by compression ultrasound or venography.
or
2. Suspected (recurrent) DVT with one of the following findings
if there were no previous DVT investigations:
• abnormal compression ultrasound (CUS)
• an intraluminal filling defect on venography
if there was a DVT investigation at screening:
• abnormal CUS where compression had been normal or, if non-compressible during screening, a substantial increase (4 mm or more) in diameter of the thrombus during full compression
• an extension of an intraluminal filling defect, or a new intraluminal filling defect or an extension of non-visualization of veins in the presence of a sudden
cut-off on venography
3. Fatal PE
• PE based on objective diagnostic testing, autopsy, or
• death which can not be attributed to a documented cause and for which PE/DVT can not be ruled out (unexplained death).
In the absence of objective testing, a suspected episode of DVT or PE will be considered as confirmed if it led to a change in anticoagulant treatment at
therapeutic dosages for more than 48 hours.

Secondary Objective:

Main Objective: For the Einstein-DVT evaluation. The primary efficacy objective is to evaluate whether rivaroxaban is at least as effective as enoxaparin/VKA in the treatment of patients with acute symptomatic deep-vein thrombosis (DVT) without
symptomatic pulmonary embolism (PE) for the prevention of recurrent venous thromboembolic events.
For the Einstein-PE evaluation. The primary efficacy objective is to evaluate whether rivaroxaban is at least as effective as enoxaparin/VKA in the treatment of patients with acute symptomatic PE with or without symptomatic DVT for the prevention of recurrent venous thromboembolic events.

Secondary ID(s)

BAY 59-7939/11702

2006-004495-13-BE