Clinical trial NCT00395772: Once-daily Oral Direct Factor Xa Inhibitor BAY59-7939 in Patients With Acute Symptomatic Deep-vein Thrombosis
Official title: Once-daily Oral Direct Factor Xa Inhibitor BAY59-7939 in Patients With Acute Symptomatic Deep-vein Thrombosis The Einstein-DVT Dose-finding Study. A Phase II Evaluation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Treatment of venous thromboembolism
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2006-11-03
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the optimal dose of BAY 59-7939 and to compare the safety and effectiveness of this new drug with the standard way of treatment of deep vein thrombosis (heparin infusion plus one of the vitamin K antagonists), taking into account new events of thrombosis and pulmonary embolism and bleeding risk.

Detailed description: Within the U.S., Johnson \& Johnson is sponsor.

Eligibility criteria: Inclusion Criteria:

* Confirmed acute symptomatic DVT, i.e. proximal or extensive calf-vein thrombosis involving at least the upper third part of the calf veins, without concomitant symptomatic PE
* Written informed consent

Exclusion Criteria:

* Legal lower age limitations (country specific)
* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT
* Other indication for VKA than PE/DVT
* More than 36 hours pre-randomization treatment with therapeutic dosages of (LMW) heparin or more than a single dose of VKA prior to randomization
* Participation in another pharmacotherapeutic study within the prior 30 days
* Creatinine clearance \< 30 mL/min, impaired liver function (transaminases \> 2 x ULN), or bacterial endocarditis
* Life expectancy \< 3 months
* Active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin
* Uncontrolled hypertension: systolic blood pressure \> 200 mmHg and diastolic blood pressure \> 110 mmHg
* Pregnancy or childbearing potential without proper contraceptive measures
* Any other contraindication listed in the labeling of warfarin, acenocoumarol, phenprocoumon, fluindione, UFH, enoxaparin, or tinzaparin
* Systemic treatment with azole compounds or other strong CYP3A4 inhibitors (e.g. ketoconazole, fluconazol, itraconazole, HIV protease inhibitors) within 4 days prior to randomization and during the study

Primary outcomes:
measure: The primary efficacy endpoint was the composite of symptomatic recurrent DVT or symptomatic fatal and non-fatal PE at 12 weeks and deterioration in thrombotic burden, as assessed by CUS and PLS, at baseline and at 12 weeks.
timeFrame: 12 weeks
Secondary outcomes:
measure: The principal safety outcome is all clinically relevant bleeding (i.e. major bleeding and clinically relevant non-major bleeding) within 12 weeks.
timeFrame: 12 weeks
measure: The separate components of the primary efficacy outcome at 12 weeks.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Albuquerque
country: United States
state: New Mexico
city: Albuquerque
country: United States
state: New Mexico
city: Chapel Hill
country: United States
state: North Carolina
city: Fredericksburg
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Canberra
country: Australia
state: Australian Capital Territory
city: Sydney
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Melbourne
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Curitiba
country: Brazil
state: Paraná
city: Porto Alegre
country: Brazil
state: RS
city: Sorocaba
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
state: SP
city: Edmonton
country: Canada
state: Alberta
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Hradec Kralove
country: Czech Republic
city: Karlovy Vary
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Plzen
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Usti nad Labem
country: Czech Republic
city: Aarhus
country: Denmark
city: Brædstrup
country: Denmark
city: Frederiksberg
country: Denmark
city: Brest Cedex
country: France
city: Grenoble
country: France
city: Montpellier Cedex
country: France
city: Paris Cedex 15
country: France
city: Paris
country: France
city: Saint-etienne
country: France
city: Valenciennes Cedex
country: France
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Safed
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Milano
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Padova
country: Italy
city: Pavia
country: Italy
city: Reggio Emilia
country: Italy
city: Venezia
country: Italy
city: Amersfoort
country: Netherlands
city: Amsterdam
country: Netherlands
city: Amsterdam
country: Netherlands
city: Arnhem
country: Netherlands
city: Groningen
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Maastricht
country: Netherlands
city: Sittard-geleen
country: Netherlands
city: Zwolle
country: Netherlands
city: Bydgoszcz
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Wroclaw
country: Poland
city: Johannesburg
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Göteborg
country: Sweden
city: Jönköping
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Västervik
country: Sweden
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Buller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS, Misselwitz F, Raskob G, Schellong S, Segers A; Einstein-DVT Dose-Ranging Study investigators. A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Blood. 2008 Sep 15;112(6):2242-7. doi: 10.1182/blood-2008-05-160143. Epub 2008 Jul 11.