- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00786422
Deep Vein Thrombosis Treatment With the Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients Using a Strong CYP 3A4 Inducer
October 20, 2015 updated by: Bayer
The EINSTEIN CYP Cohort Study Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep-vein Thrombosis or Pulmonary Embolism Using a Strong CYP 3A4 Inducer
This is a multicenter, cohort study evaluating an adapted rivaroxaban dose regimen in patients with acute, proximal deep-vein thrombosis (DVT) or acute pulmonary embolism (PE) who concomitantly use a strong cytochrome P450 isoenzyme 3A4 (CYP 3A4) inducer for the entire 3-month study duration.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The following laboratory variables were determined at baseline at the local laboratories: Hemoglobin, platelets, activated partial thromboplastin time (aPTT), international normalized ratio (INR), alanine aminotransferase (ALT), and creatinine.
Study Type
Interventional
Enrollment (Actual)
25
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Queensland
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Redcliffe, Queensland, Australia, 4020
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Wien, Austria, 1090
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Sao Paulo
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São Paulo, Sao Paulo, Brazil, 01323-001
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Bayern
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München, Bayern, Germany, 80331
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Debrecen, Hungary, 4032
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Ashkelon, Israel, 7830604
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Holon, Israel, 58100
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Pavia, Italy, 27100
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Amsterdam, Netherlands, 1105 AZ
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Gauteng
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Johannesburg, Gauteng, South Africa, 2132
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Johannesburg, Gauteng, South Africa, 2193
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Pretoria, Gauteng, South Africa, 0084
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Pretoria, Gauteng, South Africa, 0157
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Roodepoort, Gauteng, South Africa, 1724
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Western Cape
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Somerset West, Western Cape, South Africa, 7130
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Worcester, Western Cape, South Africa, 6850
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Confirmed acute symptomatic proximal deep- vein thrombosis and/or pulmonary embolism
- Concomitant use of a strong CYP 3A4 inducer, (i.e., carbamazepine, phenytoin, rifampicin/rifampin, and rifabutin)
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 deep -vein thrombosis and/or pulmonary embolism
- Other indication for vitamin K antagonist (VKA) than deep -vein thrombosis and/or pulmonary embolism
- Concomitant use of strong CYP3A4 inhibitors (e.g., HIV protease inhibitors, systemic ketoconazole)
- Use of the strong CYP 3A4 inducers phenobarbital/primidone or St John's Wort
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Rivaroxaban (Xarelto, BAY59-7939)
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Participants received 30 mg rivaroxaban bid (twice-daily) orally for the first 3 weeks followed by 20 mg rivaroxaban bid for the remainder of the 3-month treatment period.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Pharmacodynamics - Prothrombin Time (PT), Baseline Value
Time Frame: The baseline value of prothrombin time is measured or calculated at a rivaroxaban concentration of 0 µg/L and is based on the observations that were made during the 3 months treatment period
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Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade.
The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II.
The initial read-out is in seconds.
Mean and standard deviation (SD) values are presented for PT baseline.
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The baseline value of prothrombin time is measured or calculated at a rivaroxaban concentration of 0 µg/L and is based on the observations that were made during the 3 months treatment period
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Pharmacodynamics - Prothrombin Time (PT), Slope
Time Frame: Up to 3 months treatment
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Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade.
The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II.
The initial read-out of PT is in seconds.
The PT slope describes the linear increase of PT for one unit increase in concentration, thus the unit of PT slope is s*(µg/L)^-1.
The final population PK/PD model included a fixed slope that was fitted to the data of the 19 patients that were eligible for evaluation.
The estimated mean value (fixed/ the same for all patients in this study) is presented for PT slope.
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Up to 3 months treatment
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Pharmacokinetics - AUC(0-24)ss (Area Under the Measurement Versus Time Curve From Time 0 to 24 Hours After First Dosing on a Day at Steady State) of Rivaroxaban
Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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AUC(0-24)ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inducer.
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0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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Pharmacokinetics - Cmax,ss (Maximum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban
Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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Cmax,ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.
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0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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Pharmacokinetics - Cmin,ss (Minimum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban
Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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Cmin,ss was predicted for each individual participant from rivaroxaban plasma concentrations and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.
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0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
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Percentage of Participants With Clinically Relevant Bleeding (i.e. Major Bleeding and Clinically Relevant Non-major Bleeding)
Time Frame: Up to 3 months treatment and during subsequent 2 days
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All events were adjudicated and confirmed by a central independent adjudication committee.
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.
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Up to 3 months treatment and during subsequent 2 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With Symptomatic Recurrent Venous Thromboembolism [VTE] (i.e. the Composite of Recurrent Deep Vein Thrombosis [DVT] or Non-fatal or Fatal Pulmonary Embolism [PE]) Until the Intended End of Study Treatment
Time Frame: Up to 3 months treatment and during subsequent 30-day observational period for an individual participant
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All events were adjudicated and confirmed by a central independent adjudication committee.
The composite efficacy outcome symptomatic recurrent VTE was analyzed descriptively, with the components: Death due to PE, death for which PE cannot be excluded, symptomatic PE and DVT, symptomatic recurrent PE only, and symptomatic recurrent DVT only up to the end of intended treatment period (3 months; 98 study days) and on-treatment (up to 2 days after stop of study drug).
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Up to 3 months treatment and during subsequent 30-day observational period for an individual participant
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Percentage of Participants With All Deaths
Time Frame: Up to 3 months and on-treatment (up to 2 days after stop of study drug) plus an observational period planned for one month
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All deaths were adjudicated by a central independent adjudication committee.
Participants who died for any reason were counted for this measure.
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Up to 3 months and on-treatment (up to 2 days after stop of study drug) plus an observational period planned for one month
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Percentage of Participants With Treatment Emergent Deaths - 7 Days Window
Time Frame: Up to 3 months treatment and during subsequent 7 days
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Treatment emergent deaths were adjudicated by a central independent adjudication committee.
Participants who died from treatment emergent adverse events were counted for this measure.
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Up to 3 months treatment and during subsequent 7 days
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Percentage of Participants With Other Vascular Events
Time Frame: Up to 3 months treatment and during subsequent 1 day
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All events were adjudicated and confirmed by a central independent adjudication committee.
Other vascular events comprised ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), unstable angina (UA), ischemic stroke, transient ischemic attack (TIA), non-central nervous system systemic embolism and vascular death.
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Up to 3 months treatment and during subsequent 1 day
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2009
Primary Completion (Actual)
May 1, 2011
Study Completion (Actual)
June 1, 2011
Study Registration Dates
First Submitted
November 5, 2008
First Submitted That Met QC Criteria
November 5, 2008
First Posted (Estimate)
November 6, 2008
Study Record Updates
Last Update Posted (Estimate)
November 18, 2015
Last Update Submitted That Met QC Criteria
October 20, 2015
Last Verified
October 1, 2015
More Information
Terms related to this study
Keywords
- Additional relevant MeSH terms:
- Respiratory Tract Diseases
- Vascular Diseases
- Cardiovascular Diseases
- Embolism
- Thrombosis
- Lung Diseases
- Enzyme Inhibitors
- Pharmacologic Actions
- Human Immunodeficiency Virus (HIV)
- Cohort Study
- Anticoagulants
- Therapeutic Uses
- Pulmonary Embolism
- Cardiovascular Agents
- Venous Thrombosis
- Embolism and Thrombosis
- Hematologic Agents
- Fibrin Modulating Agents
- Neurologic disease
- Enzyme Inducers
- CYP Inducers
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13238
- 2008-003303-31 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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