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Once - Daily Oral Direct Factor Xa Inhibitor Rivaroxaban In The Long-Term Prevention Of Recurrent Symptomatic Venous Thromboembolism In Patients With Symptomatic Deep-Vein Thrombosis Or Pulmonary Embolism. The Einstein-Extension Study

Primary Purpose

Venous Thromboembolism

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Rivaroxaban (Xarelto, BAY59-7939)

Placebo

About this trial

This is an interventional prevention trial for Venous Thromboembolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with confirmed symptomatic PE or DVT who have been treated for 6 or 12 months with VKA or rivaroxaban

Exclusion Criteria:

Legal lower age limitations (country specific)
Indication for VKA other than DVT and/or PE
Patients in whom anticoagulant treatment for their index PE or DVT should be continued
Childbearing potential without proper contraceptive measures, pregnancy or breast feeding. Proper contraceptive measures are defined as a method of contraception with a failure rate < 1 % during the course of the study (including the observational period). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP [Committee for Proprietary Medicinal Products]/ICH [International Conference on Harmonization]/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence and vasectomy

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rivaroxaban (Xarelto, BAY59-7939)

Placebo

Arm Description

Participants were to receive rivaroxaban 20 mg oral tablet once daily

Participants were to receive matching placebo oral tablet once daily

Outcomes

Primary Outcome Measures

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

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. For definition of DVT/PE, kindly refer to the link in the Protocol section.

Secondary Outcome Measures

Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE and All Cause Mortality Until the Intended End of Study Treatment

Percentage of Participants With the Composite Variable Comprising Recurrent DVT, Non-fatal PE, All Cause Mortality, Strokes and Myocardial Infarctions Until the Intended End of Study Treatment

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), results/films/images of confirmatory testing, and/or case summaries.

Percentage of Participants With Net Clinical Benefit as Composite of Recurrent DVT or Non-fatal or Fatal PE and Major Bleeding Events Until the Intended End of Study Treatment

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 Recurrent VTE (PE or DVT) Until the Intended End of Study Treatment

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), results/films/images of confirmatory testing, and/or case summaries.

Percentage of Participants With Recurrent DVT Until the Intended End of Study Treatment

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 Major Bleeding

All events were adjudicated and confirmed by a central independent adjudication committee (CIAC) blinded to treatment. Major bleeding event was overt bleeding associated with a 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. Treatment-emergent [after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)] events and all events post randomization were reported.

Percentage of Participants With Clinically Relevant Bleeding

All events adjudicated/confirmed by CIAC blinded to treatment. Clinically relevant bleeding included major bleeding (definition: see outcome 7) 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 daily life activities. Treatment-emergent events (after intake of 1st study medication tablet as randomized up to 2 days after stop of study medication ['time window: 2 days']) and all events post randomization were reported

Percentage of Participants With All Death

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. Treatment-emergent events and all events post randomization were reported. Treatment-emergent: after intake of first tablet of study medication as randomized but not more than 2 days after stop of study medication (referred to as time window: 2 days)

Percentage of Participants With Other Vascular Events

All pre-defined vascular events (acute coronary syndromes, ischemic stroke, transient ischemic attack, non-central nervous system systemic embolism and vascular death) were adjudicated/confirmed by a central independent adjudication committee blinded to treatment, based on results/films/images of confirmatory testing, and/or case summaries. On treatment events and all events post randomization were reported. On treatment: after intake of first tablet of study medication as randomized but not more than 1 day after stop of study medication (referred to as time window: 1 day)

Full Information

NCT ID

NCT00439725

First Posted

February 23, 2007

Last Updated

October 28, 2014

Sponsor

Bayer

Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

1. Study Identification

Unique Protocol Identification Number

NCT00439725

Brief Title

Once - Daily Oral Direct Factor Xa Inhibitor Rivaroxaban In The Long-Term Prevention Of Recurrent Symptomatic Venous Thromboembolism In Patients With Symptomatic Deep-Vein Thrombosis Or Pulmonary Embolism. The Einstein-Extension Study

Official Title

Once-daily Oral Direct Factor Xa Inhibitor Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism. The Einstein-Extension Study

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Completed

Study Start Date

February 2007 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, event-driven, superiority study for efficacy. Patients with confirmed symptomatic DVT (deep vein thrombosis) or PE (pulmonary embolism) who completed 6 or 12 months of treatment with rivaroxaban or VKA (vitamin K antagonist) are eligible for this trial (Einstein-Extension study).

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Venous Thromboembolism

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1197 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rivaroxaban (Xarelto, BAY59-7939)

Arm Type

Experimental

Arm Description

Participants were to receive rivaroxaban 20 mg oral tablet once daily

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants were to receive matching placebo oral tablet once daily

Intervention Type

Drug

Intervention Name(s)

Rivaroxaban (Xarelto, BAY59-7939)

Intervention Description

Patients randomized to rivaroxaban will receive rivaroxaban 20 mg once-daily.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Patients allocated to placebo will receive a matching placebo tablet once daily.

Primary Outcome Measure Information:

Title

Description

Time Frame