Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Pulmonary Embolism - The EINSTEIN PE Study
- Conditions
- Pulmonary Embolism
- Interventions
- Registration Number
- NCT00439777
- Lead Sponsor
- Bayer
- Brief Summary
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 pulmonary embolism (PE) with or without symptomatic Deep-Vein Thrombosis (DVT) (Einstein-PE).
- Detailed Description
Within the US 'Johnson \& Johnson Pharmaceutical Research \& Development, L.L.C.' is sponsor.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4833
- Confirmed acute symptomatic proximal PE with or without symptomatic DVT
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rivaroxaban (Xarelto, BAY59-7939) Rivaroxaban (Xarelto, BAY59-7939) Participants received 15 mg rivaroxaban (oral) twice daily (b.i.d.) for 3 weeks, followed by 20 mg once daily (o.d.) Enoxaparin/VKA Enoxaparin overlapping with and followed by VKA Participants received enoxaparin (subcutaneous) 1.0 mg/kg b.i.d. for minimal 5 days, plus vitamin K antagonist (VKA) at individually titrated doses to achieve a target international normalized ratio (INR) of 2.5 (range: 2.0 - 3.0)
- Primary Outcome Measures
Name Time Method 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment 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 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 PE Until the Intended End of Study Treatment 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 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 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) 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 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) 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.