Clinical trial NCT00786422: Deep Vein Thrombosis Treatment With the Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients Using a Strong CYP 3A4 Inducer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thrombosis
Deep Vein Thrombosis
Keywords: Embolism and Thrombosis
Pulmonary Embolism
Embolism
Venous Thrombosis
Thrombosis
Enzyme Inducers
CYP Inducers
Cohort Study
Pharmacologic Actions
Respiratory Tract Diseases
Lung Diseases
Vascular Diseases
Human Immunodeficiency Virus (HIV)
Neurologic disease
Additional relevant MeSH terms:
Fibrin Modulating Agents
Anticoagulants
Therapeutic Uses
Hematologic Agents
Enzyme Inhibitors
Cardiovascular Diseases
Cardiovascular Agents
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2008-11-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamics - Prothrombin Time (PT), Baseline Value
timeFrame: 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
measure: Pharmacodynamics - Prothrombin Time (PT), Slope
timeFrame: Up to 3 months treatment
measure: 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
timeFrame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
measure: Pharmacokinetics - Cmax,ss (Maximum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban
timeFrame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
measure: Pharmacokinetics - Cmin,ss (Minimum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban
timeFrame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban
measure: Percentage of Participants With Clinically Relevant Bleeding (i.e. Major Bleeding and Clinically Relevant Non-major Bleeding)
timeFrame: Up to 3 months treatment and during subsequent 2 days
Secondary outcomes:
measure: 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
timeFrame: Up to 3 months treatment and during subsequent 30-day observational period for an individual participant
measure: Percentage of Participants With All Deaths
timeFrame: Up to 3 months and on-treatment (up to 2 days after stop of study drug) plus an observational period planned for one month
measure: Percentage of Participants With Treatment Emergent Deaths - 7 Days Window
timeFrame: Up to 3 months treatment and during subsequent 7 days
measure: Percentage of Participants With Other Vascular Events
timeFrame: Up to 3 months treatment and during subsequent 1 day
Other outcomes:
Locations:
city: Redcliffe
country: Australia
state: Queensland
city: Wien
country: Austria
city: São Paulo
country: Brazil
state: Sao Paulo
city: München
country: Germany
state: Bayern
city: Debrecen
country: Hungary
city: Ashkelon
country: Israel
city: Holon
country: Israel
city: Pavia
country: Italy
city: Amsterdam
country: Netherlands
city: Johannesburg
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Roodepoort
country: South Africa
state: Gauteng
city: Somerset West
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: