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Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis - The EINSTEIN DVT Study

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00440193
First Posted: February 26, 2007
Last Update Posted: February 27, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
February 23, 2007
February 26, 2007
November 22, 2012
January 24, 2013
February 27, 2014
March 2007
April 2010   (Final data collection date for primary outcome measure)
Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment [ Time Frame: 3-, 6- or 12-month study treatment period ]
All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), and/or case summaries.
Not Provided
Complete list of historical versions of study NCT00440193 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With an Event for Net Clinical Benefit 1 Until the Intended End of Study Treatment [ Time Frame: 3-, 6- or 12-month study treatment period ]
    Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE, and major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With Clinically Relevant Bleeding, Treatment-emergent (Time Window: Until 2 Days After Last Dose) [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life.
  • Percentage of Participants With All Deaths [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either autopsy, results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With Other Vascular Events, On-treatment (Time Window: Until 1 Day After Last Dose) [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All pre-defined vascular events (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism or vascular death) were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based results/films/images of confirmatory testing, and/or case summaries.
Not Provided
  • Percentage of Participants With the Individual Components of Efficacy Outcomes Until the Intended End of Study Treatment [ Time Frame: 3-, 6- or 12-month study treatment period ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
  • Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Fatal or Non-fatal Pulmonary Embolism [PE]) During Observational Period [ Time Frame: Up to 30 days after the last intake of study medication ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for fatal PE) or unexplained death for which DVT/PE could not be ruled out (for fatal PE), results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality During Observational Period [ Time Frame: Up to 30 days after the last intake of study medication ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound (for DVT), venography (for DVT), spiral computed tomography (CT) scanning (for PE), pulmonary angiography (for PE), ventilation/perfusion lung scan (for PE), lung scintigraphy (for PE), autopsy (for deaths), results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With an Event for Net Clinical Benefit 1 During Observational Period [ Time Frame: Up to 30 days after the last intake of study medication ]
    Net clinical benefit 1: composite of recurrent DVT or non-fatal or fatal PE or major bleeding. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death. Net clinical benefit was considered greater in those participants with fewer composite events. All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With Recurrent DVT During Observational Period [ Time Frame: Up to 30 days after the last intake of study medication ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment. Events were assessed based on either compression ultrasound, venography, results/films/images of confirmatory testing, and/or case summaries.
  • Percentage of Participants With the Individual Components of Efficacy Outcomes During Observational Period [ Time Frame: Up to 30 days after the last intake of study medication ]
    All events were adjudicated and confirmed by a central independent adjudication committee blinded to treatment, based on either compression ultrasound, venography, spiral computed tomography scanning, pulmonary angiography, ventilation/perfusion lung scan, lung scintigraphy, autopsy or unexplained death for which DVT/PE could not be ruled out, results/films/images of confirmatory testing, and/or case summaries. Major bleeding was overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of ≥2 units, occurring in a critical site or contributing to death.
Not Provided
 
Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis - The EINSTEIN DVT Study
Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism
This is a multicenter, randomized, open-label, assessor-blind, event-driven, non-inferiority program for efficacy with a study treatment duration of 3, 6 or 12 months in patients with confirmed acute symptomatic DVT without symptomatic PE (Einstein-DVT).

Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

The treatment period was followed by an observational period of 30 days starting the day after the last intake of study medication, regardless of the actual duration of study drug administration. Participants who did not complete the treatment period also entered the observational period. It was also possible that participants did not enter the observational period, e.g. due to withdrawal of consent or termination of study participation. Participants who were transferring from study 11702 DVT (NCT00440193) to the extension study 11899 (NCT00439725) did not enter the observational period.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Venous Thrombosis
  • Drug: Rivaroxaban (Xarelto, BAY59-7939)
    During the first 3 weeks patients will receive 15 mg rivaroxaban twice-daily. Thereafter, patients will receive rivaroxaban 20 mg once-daily. Rivaroxaban will be administered orally and should be taken with food.
  • Drug: Enoxaparin followed by VKA
    Enoxaparin 1.0 mg/kg twice daily with a minimal duration of 5 days. This 5 days treatment could include the period up to 36 h before randomization if enoxaparin twice-daily was used. VKA should be started as soon as possible but not later than 48 hours after randomization.
  • Experimental: Rivaroxaban (Xarelto, BAY59-7939)
    Participants were to receive rivaroxaban 15 mg oral tablet twice daily for 3 weeks, followed by 20 mg once daily
    Intervention: Drug: Rivaroxaban (Xarelto, BAY59-7939)
  • Active Comparator: Enoxaparin/VKA
    Participants were to receive 1.0 mg/kg enoxaparin twice daily (subcutaneous) for at least 5 days, plus vitamin K antagonist (VKA) (oral) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 to 3.0)
    Intervention: Drug: Enoxaparin followed by VKA

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3449
April 2010
April 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Confirmed acute symptomatic proximal DVT without symptomatic PE

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 and/or PE
  • Other indication for VKA than DVT and/or PE
  • The pre-randomization anti-coagulant treatment (Criteria # 4) has been prolonged from 36 hours to a maximum of 48 hours.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Hungary,   India,   Indonesia,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Netherlands,   New Zealand,   Norway,   Philippines,   Poland,   Puerto Rico,   Singapore,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   United Kingdom,   United States
Andorra,   Argentina,   Estonia,   Ireland,   Latvia,   Lithuania,   Peru,   Portugal,   Slovakia
 
NCT00440193
11702a
2006-004495-13 ( EudraCT Number )
11702b ( Other Identifier: Company internal )
Yes
Not Provided
Not Provided
Bayer
Bayer
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study Director: Bayer Study Director Bayer
Bayer
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP