Clinical trial NCT00558259: Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE
Official title: Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long-term Prevention of Recurrent Symptomatic Proximal Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 1353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary efficacy objective is to evaluate whether dabigatran etexilate is superior to placebo in the long-term prevention of recurrent symptomatic venous thrombo-embolism (VTE) in patients with symptomatic deep-vein thrombosis (DVT) or pulmonary embolism (PE) who completed 6 to 18 months of treatment with vitamin K antagonist (VKA).


Eligibility criteria: Inclusion criteria:

1. Patients with confirmed symptomatic PE or proximal DVT of the leg(s) who have been treated for 6 to 18 months with therapeutic dosages (intended INR between 2-3) of an oral VKA (e.g. warfarin, acenocoumarol, phenprocoumon, or fluindione) or RE-COVER study medication up to the moment of screening for the current study.
2. Written informed consent

Exclusion criteria:

1. Younger then 18 years of age
2. Indication for VKA other than DVT and/or PE
3. Patients in whom anticoagulant treatment for their index PE or DVT should be continued
4. Active liver disease or liver disease decreasing survival (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT \> 3 x ULN
5. Creatinine clearance \< 30 ml/min
6. Acute bacterial endocarditis
7. Active bleeding or high risk for bleeding.
8. Uncontrolled hypertension (investigators judgement)
9. Intake of another experimental drug within the 30 days prior to randomization into the study
10. Life expectancy \<6 months
11. Childbearing potential without proper contraceptive measures\*, pregnancy or breast feeding

Primary outcomes:
measure: Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Including Unexplained Death During the Intended Treatment Period
timeFrame: 6 months
Secondary outcomes:
measure: Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Excluding Unexplained Death During the Intended Treatment Period
timeFrame: 6 months
measure: Centrally Confirmed Symptomatic Recurrent Deep Venous Thrombotic (DVT) Events During the Intended Treatment Period
timeFrame: 6 months
measure: Centrally Confirmed Symptomatic Pulmonary Embolism (PE) Events During the Intended Treatment Period
timeFrame: 6 months
measure: Centrally Confirmed Unexplained Deaths During the Intended Treatment Period
timeFrame: 6 months
measure: Centrally Confirmed Bleeding Event During the Treatment Period
timeFrame: 6 months
measure: Centrally Confirmed Cardiovascular Events During the Treatment Period
timeFrame: 6 months
measure: Laboratory Measures, Especially Liver Function Tests (LFTs)
timeFrame: 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1160.63.01025 Boehringer Ingelheim Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: 1160.63.01023 Boehringer Ingelheim Investigational Site
state: Alabama
city: Laguna Hills
country: United States
facility: 1160.63.01002 Boehringer Ingelheim Investigational Site
state: California
city: Colorado Springs
country: United States
facility: 1160.63.01014 Boehringer Ingelheim Investigational Site
state: Colorado
city: Jacksonville
country: United States
facility: 1160.63.01003 Boehringer Ingelheim Investigational Site
state: Florida
city: Key West
country: United States
facility: 1160.63.01030 Boehringer Ingelheim Investigational Site
state: Florida
city: Lafayette
country: United States
facility: 1160.63.01022 Boehringer Ingelheim Investigational Site
state: Louisiana
city: New Iberia
country: United States
facility: 1160.63.01044 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Biddeford
country: United States
facility: 1160.63.01017 Boehringer Ingelheim Investigational Site
state: Maine
city: Salisbury
country: United States
facility: 1160.63.01004 Boehringer Ingelheim Investigational Site
state: Maryland
city: Worcester
country: United States
facility: 1160.63.01016 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: St. Louis
country: United States
facility: 1160.63.01037 Boehringer Ingelheim Investigational Site
state: Missouri
city: Missoula
country: United States
facility: 1160.63.01019 Boehringer Ingelheim Investigational Site
state: Montana
city: Columbus
country: United States
facility: 1160.63.01032 Boehringer Ingelheim Investigational Site
state: Ohio
city: Uniontown
country: United States
facility: 1160.63.01001 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Uniontown
country: United States
facility: 1160.63.01024 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1160.63.01005 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1160.63.01020 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Salt Lake City
country: United States
facility: 1160.63.01011 Boehringer Ingelheim Investigational Site
state: Utah
city: Richmond
country: United States
facility: 1160.63.01007 Boehringer Ingelheim Investigational Site
state: Virginia
city: Bellevue
country: United States
facility: 1160.63.01035 Boehringer Ingelheim Investigational Site
state: Washington
city: Greenslopes
country: Australia
facility: 1160.63.61002 Boehringer Ingelheim Investigational Site
state: Queensland
city: Elizabeth Vale
country: Australia
facility: 1160.63.61003 Boehringer Ingelheim Investigational Site
state: South Australia
city: Clayton
country: Australia
facility: 1160.63.61001 Boehringer Ingelheim Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: 1160.63.61004 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Graz
country: Austria
facility: 1160.63.43005 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 1160.63.43006 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1160.63.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1160.63.43002 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1160.63.43004 Boehringer Ingelheim Investigational Site
city: Aalst
country: Belgium
facility: 1160.63.32005 Boehringer Ingelheim Investigational Site
city: Duffel
country: Belgium
facility: 1160.63.32004 Boehringer Ingelheim Investigational Site
city: Kortrijk
country: Belgium
facility: 1160.63.32003 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1160.63.32001 Boehringer Ingelheim Investigational Site
city: Lier
country: Belgium
facility: 1160.63.32002 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1160.63.02013 Boehringer Ingelheim Investigational Site
state: Alberta
city: Saint John
country: Canada
facility: 1160.63.02004 Boehringer Ingelheim Investigational Site
state: New Brunswick
city: Hamilton
country: Canada
facility: 1160.63.02005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: 1160.63.02020 Boehringer Ingelheim Investigational Site
city: Ceske Budejovice
country: Czech Republic
facility: 1160.63.42004 Boehringer Ingelheim Investigational Site
city: Jablonec nad Nisou
country: Czech Republic
facility: 1160.63.42003 Boehringer Ingelheim Investigational Site
city: Kladno
country: Czech Republic
facility: 1160.63.42008 Boehringer Ingelheim Investigational Site
city: Liberec
country: Czech Republic
facility: 1160.63.42012 Boehringer Ingelheim Investigational Site
city: Nymburk
country: Czech Republic
facility: 1160.63.42010 Boehringer Ingelheim Investigational Site
city: Ostrava-Vitkovice
country: Czech Republic
facility: 1160.63.42011 Boehringer Ingelheim Investigational Site
city: Ostrava
country: Czech Republic
facility: 1160.63.42009 Boehringer Ingelheim Investigational Site
city: Prague 4-Krc
country: Czech Republic
facility: 1160.63.42002 Boehringer Ingelheim Investigational Site
city: Prague 4
country: Czech Republic
facility: 1160.63.42001 Boehringer Ingelheim Investigational Site
city: Praha 4
country: Czech Republic
facility: 1160.63.42006 Boehringer Ingelheim Investigational Site
city: Prostejov
country: Czech Republic
facility: 1160.63.42005 Boehringer Ingelheim Investigational Site
city: Rakovnik
country: Czech Republic
facility: 1160.63.42007 Boehringer Ingelheim Investigational Site
city: Slany
country: Czech Republic
facility: 1160.63.42013 Boehringer Ingelheim Investigational Site
city: Tabor
country: Czech Republic
facility: 1160.63.42014 Boehringer Ingelheim Investigational Site
city: Kohtla-Järve
country: Estonia
facility: 1160.63.37202 Boehringer Ingelheim Investigational Site
city: Tallin
country: Estonia
facility: 1160.63.37203 Boehringer Ingelheim Investigational Site
city: Tartu
country: Estonia
facility: 1160.63.37201 Boehringer Ingelheim Investigational Site
city: Darmstadt
country: Germany
facility: 1160.63.49013 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1160.63.49017 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1160.63.49018 Boehringer Ingelheim Investigational Site
city: Gießen
country: Germany
facility: 1160.63.49014 Boehringer Ingelheim Investigational Site
city: Ludwigshafen
country: Germany
facility: 1160.63.49011 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1160.63.49005 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1160.63.49010 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1160.63.49007 Boehringer Ingelheim Investigational Site
city: Püttlingen
country: Germany
facility: 1160.63.49009 Boehringer Ingelheim Investigational Site
city: Bergamo
country: Italy
facility: 1160.63.39006 Boehringer Ingelheim Investigational Site
city: Castelfranco Veneto (TV)
country: Italy
facility: 1160.63.39015 Boehringer Ingelheim Investigational Site
city: Chieti Scalo (CH)
country: Italy
facility: 1160.63.39019 Boehringer Ingelheim Investigational Site
city: Cosenza
country: Italy
facility: 1160.63.39003 Boehringer Ingelheim Investigational Site
city: Fidenza (PR)
country: Italy
facility: 1160.63.39008 Boehringer Ingelheim Investigational Site
city: Firenze
country: Italy
facility: 1160.63.39011 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1160.63.39009 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1160.63.39004 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1160.63.39010 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1160.63.39020 Boehringer Ingelheim Investigational Site
city: Napoli
country: Italy
facility: 1160.63.39022 Boehringer Ingelheim Investigational Site
city: Palermo
country: Italy
facility: 1160.63.39001 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1160.63.39007 Boehringer Ingelheim Investigational Site
city: Rimini
country: Italy
facility: 1160.63.39012 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1160.63.39017 Boehringer Ingelheim Investigational Site
city: Treviso
country: Italy
facility: 1160.63.39014 Boehringer Ingelheim Investigational Site
city: Udine
country: Italy
facility: 1160.63.39002 Boehringer Ingelheim Investigational Site
city: Vittorio veneto (TV)
country: Italy
facility: 1160.63.39016 Boehringer Ingelheim Investigational Site
city: Gwangju-si
country: Korea, Republic of
facility: 1160.63.82010 Boehringer Ingelheim Investigational Site
city: Incheon
country: Korea, Republic of
facility: 1160.63.82003 Boehringer Ingelheim Investigational Site
city: Kyeonggi-do
country: Korea, Republic of
facility: 1160.63.82005 Boehringer Ingelheim Investigational Site
city: Kyunggi-do
country: Korea, Republic of
facility: 1160.63.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1160.63.82004 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1160.63.82006 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1160.63.82008 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1160.63.82011 Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: 1160.63.82007 Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: 1160.63.37101 Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: 1160.63.37102 Boehringer Ingelheim Investigational Site
city: Kaunas
country: Lithuania
facility: 1160.63.37002 Boehringer Ingelheim Investigational Site
city: Vilnius
country: Lithuania
facility: 1160.63.37001 Boehringer Ingelheim Investigational Site
city: Assen
country: Netherlands
facility: 1160.63.31010 Boehringer Ingelheim Investigational Site
city: Breda
country: Netherlands
facility: 1160.63.31006 Boehringer Ingelheim Investigational Site
city: Den Haag
country: Netherlands
facility: 1160.63.31007 Boehringer Ingelheim Investigational Site
city: Den Helder
country: Netherlands
facility: 1160.63.31011 Boehringer Ingelheim Investigational Site
city: Dirksland
country: Netherlands
facility: 1160.63.31012 Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: 1160.63.31003 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 1160.63.31001 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 1160.63.31009 Boehringer Ingelheim Investigational Site
city: Oss
country: Netherlands
facility: 1160.63.31008 Boehringer Ingelheim Investigational Site
city: Christchurch
country: New Zealand
facility: 1160.63.64002 Boehringer Ingelheim Investigational Site
city: Kielce
country: Poland
facility: 1160.63.48010 Boehringer Ingelheim Investigational Site
city: Poznan
country: Poland
facility: 1160.63.48003 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48001 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48002 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48004 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48005 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48006 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48007 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.63.48008 Boehringer Ingelheim Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: 1160.63.07007 Boehringer Ingelheim Investigational Site
city: Kursk
country: Russian Federation
facility: 1160.63.07004 Boehringer Ingelheim Investigational Site
city: Ufa
country: Russian Federation
facility: 1160.63.07014 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1160.63.07005 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1160.63.07006 Boehringer Ingelheim Investigational Site
city: Singapore
country: Singapore
facility: 1160.63.65001 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1160.63.27003 Boehringer Ingelheim Investigational Site
city: Centurion
country: South Africa
facility: 1160.63.27007 Boehringer Ingelheim Investigational Site
city: Krugersdorp
country: South Africa
facility: 1160.63.27009 Boehringer Ingelheim Investigational Site
city: Somerset West
country: South Africa
facility: 1160.63.27001 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1160.63.46001 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1160.63.46006 Boehringer Ingelheim Investigational Site
city: Lund
country: Sweden
facility: 1160.63.46002 Boehringer Ingelheim Investigational Site
city: Mölndal
country: Sweden
facility: 1160.63.46004 Boehringer Ingelheim Investigational Site
city: Skövde
country: Sweden
facility: 1160.63.46007 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1160.63.46005 Boehringer Ingelheim Investigational Site
city: Värnamo
country: Sweden
facility: 1160.63.46003 Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: 1160.63.41012 Boehringer Ingelheim Investigational Site
city: Bruderholz
country: Switzerland
facility: 1160.63.41011 Boehringer Ingelheim Investigational Site
city: Cham
country: Switzerland
facility: 1160.63.41003 Boehringer Ingelheim Investigational Site
city: Glarus
country: Switzerland
facility: 1160.63.41001 Boehringer Ingelheim Investigational Site
city: Luzern 16
country: Switzerland
facility: 1160.63.41016 Boehringer Ingelheim Investigational Site
city: Luzern
country: Switzerland
facility: 1160.63.41014 Boehringer Ingelheim Investigational Site
city: Schiers
country: Switzerland
facility: 1160.63.41005 Boehringer Ingelheim Investigational Site
city: Thun
country: Switzerland
facility: 1160.63.41009 Boehringer Ingelheim Investigational Site
city: Wetzikon
country: Switzerland
facility: 1160.63.41022 Boehringer Ingelheim Investigational Site
city: Zug
country: Switzerland
facility: 1160.63.41008 Boehringer Ingelheim Investigational Site
city: Zurich
country: Switzerland
facility: 1160.63.41006 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1160.63.66002 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1160.63.66003 Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: 1160.63.66004 Boehringer Ingelheim Investigational Site
city: Chiang Mai
country: Thailand
facility: 1160.63.66001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, Brueckmann M, Fraessdorf M, Yusuf S, Schulman S. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013 Nov 19;128(21):2325-32. doi: 10.1161/CIRCULATIONAHA.113.002332. Epub 2013 Sep 30.
citation: Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697.