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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-003303-31 | EudraCT Number |
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| Name | Class |
|---|---|
| Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rivaroxaban (Xarelto, BAY59-7939) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rivaroxaban (Xarelto, BAY59-7939) | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics - Prothrombin Time (PT), Baseline Value | 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. | 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 |
| Pharmacodynamics - Prothrombin Time (PT), Slope | 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. | Up to 3 months treatment |
| 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 | 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. | 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
| Pharmacokinetics - Cmax,ss (Maximum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Redcliffe | Queensland | 4020 | Australia | |||
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| Label | URL |
|---|---|
| Click here and search for information of Bayer products for Europe | View source |
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Out of 25 participants screened, 25 participants were assigned to treatment.
Participants with confirmed acute proximal symptomatic deep vein thrombosis (DVT) or acute pulmonary embolism (PE) were recruited at specialized study sites.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rivaroxaban (Xarelto, BAY59-7939) | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Rivaroxaban Treatment |
|
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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.
| 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
| Pharmacokinetics - Cmin,ss (Minimum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban | 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. | 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
| Percentage of Participants With Clinically Relevant Bleeding (i.e. Major Bleeding and Clinically Relevant Non-major Bleeding) | 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. | Up to 3 months treatment and during subsequent 2 days |
| Up to 3 months treatment and during subsequent 30-day observational period for an individual participant |
| Percentage of Participants With All Deaths | All deaths were adjudicated by a central independent adjudication committee. Participants who died for any reason were counted for this measure. | Up to 3 months and on-treatment (up to 2 days after stop of study drug) plus an observational period planned for one month |
| Percentage of Participants With Treatment Emergent Deaths - 7 Days Window | Treatment emergent deaths were adjudicated by a central independent adjudication committee. Participants who died from treatment emergent adverse events were counted for this measure. | Up to 3 months treatment and during subsequent 7 days |
| Percentage of Participants With Other Vascular Events | 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. | Up to 3 months treatment and during subsequent 1 day |
| Vienna |
| State of Vienna |
| 1090 |
| Austria |
| São Paulo | São Paulo | 01323-001 | Brazil |
| München | Bavaria | 80331 | Germany |
| Debrecen | 4032 | Hungary |
| Ashkelon | 7830604 | Israel |
| Holon | 58100 | Israel |
| Pavia | 27100 | Italy |
| Amsterdam | 1105 AZ | Netherlands |
| Johannesburg | Gauteng | 2132 | South Africa |
| Johannesburg | Gauteng | 2193 | South Africa |
| Pretoria | Gauteng | 0084 | South Africa |
| Pretoria | Gauteng | 0157 | South Africa |
| Roodepoort | Gauteng | 1724 | South Africa |
| Somerset West | Western Cape | 7130 | South Africa |
| Worcester | Western Cape | 6850 | South Africa |
| COMPLETED |
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| NOT COMPLETED |
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| Follow-up Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | Rivaroxaban (Xarelto, BAY59-7939) | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | Participants |
| ||||||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||||||||
| Race | Number | Participants |
| ||||||||||||||||||||||||||
| Creatinine clearance | Volume of blood plasma cleared of creatinine per time unit | Number | Participants |
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| Region of recruitment | Number | Participants |
| ||||||||||||||||||||||||||
| Participants with history of tuberculosis | Number | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacodynamics - Prothrombin Time (PT), Baseline Value | 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. | The pharmacokinetics/pharmacodynamics (PK/PD) population included all participants who received at least 1 dose of rivaroxaban and had at least 1 valid PK/PD sample after first administration | Posted | Mean | Standard Deviation | Seconds | 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 |
|
|
| |||||||||||||||||||||||||
| Primary | Pharmacodynamics - Prothrombin Time (PT), Slope | 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. | The pharmacokinetics/pharmacodynamics (PK/PD) population included all participants who received at least 1 dose of rivaroxaban and had at least 1 valid PK/PD sample after first administration | Posted | Number | s*(µg/L)^-1 | Up to 3 months treatment |
|
| |||||||||||||||||||||||||||
| Primary | 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 | 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. | The pharmacokinetics/pharmacodynamics (PK/PD) population included all participants who received at least 1 dose of rivaroxaban and had at least 1 valid PK/PD sample after first administration | Posted | Median | 90% Confidence Interval | (µg*h)/L | 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
|
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| Primary | Pharmacokinetics - Cmax,ss (Maximum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban | 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. | The pharmacokinetics/pharmacodynamics (PK/PD) population included all participants who received at least 1 dose of rivaroxaban and had at least 1 valid PK/PD sample after first administration | Posted | Median | 90% Confidence Interval | µg/L | 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
|
| ||||||||||||||||||||||||||
| Primary | Pharmacokinetics - Cmin,ss (Minimum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban | 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. | The pharmacokinetics/pharmacodynamics (PK/PD) population included all participants who received at least 1 dose of rivaroxaban and had at least 1 valid PK/PD sample after first administration | Posted | Median | 90% Confidence Interval | µg/L | 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban |
|
| ||||||||||||||||||||||||||
| Primary | Percentage of Participants With Clinically Relevant Bleeding (i.e. Major Bleeding and Clinically Relevant Non-major Bleeding) | 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. | The safety population consisted of all participants who received at least 1 dose of rivaroxaban. | Posted | Number | Percentage of participants | Up to 3 months treatment and during subsequent 2 days |
|
| |||||||||||||||||||||||||||
| Secondary | 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 | 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). | The safety population consisted of all participants who received at least 1 dose of rivaroxaban. | Posted | Number | Percentage of participants | Up to 3 months treatment and during subsequent 30-day observational period for an individual participant |
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With All Deaths | All deaths were adjudicated by a central independent adjudication committee. Participants who died for any reason were counted for this measure. | All participants | Posted | Number | Percentage of participants | Up to 3 months and on-treatment (up to 2 days after stop of study drug) plus an observational period planned for one month |
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Treatment Emergent Deaths - 7 Days Window | Treatment emergent deaths were adjudicated by a central independent adjudication committee. Participants who died from treatment emergent adverse events were counted for this measure. | All participants | Posted | Number | Percentage of participants | Up to 3 months treatment and during subsequent 7 days |
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Other Vascular Events | 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. | The safety population consisted of all participants who received at least 1 dose of rivaroxaban. | Posted | Number | Percentage of participants | Up to 3 months treatment and during subsequent 1 day |
|
|
For the whole study, adverse event (AE) data were collected during the study course of 25 months. For the individual patient, AE were collected during a treatment period planned for three months plus an observational period planned for one month.
Abbreviations used:Human Immunodeficiency Virus (HIV)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rivaroxaban (Xarelto, BAY59-7939) | 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. | 5 | 25 | 14 | 25 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Meningitis cryptococcal | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vascular dementia | Nervous system disorders | MedDRA (14.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Non-systematic Assessment |
| |
| HIV test positive | Investigations | MedDRA (14.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
| |
| Vein pain | Vascular disorders | MedDRA (14.0) | Non-systematic Assessment |
|
The investigator, whilst free to utilize data derived from the study for scientific purposes, must discuss any publication with Bayer prior to release and obtain written consent of Bayer on the intended publication. The investigator must send a draft manuscript of the publication or abstract to Bayer thirty days in advance of submission in order to obtain approval prior to submission of the final version for publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | BAYER | clinical-trials-contact@bayerhealthcare.com |
| ID | Term |
|---|---|
| D020246 | Venous Thrombosis |
| D016769 | Embolism and Thrombosis |
| D011655 | Pulmonary Embolism |
| D004617 | Embolism |
| D013927 | Thrombosis |
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
| D014652 | Vascular Diseases |
| D000163 | Acquired Immunodeficiency Syndrome |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069552 | Rivaroxaban |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Title | Measurements |
|---|---|
|
| Other (mixed South African descent) |
|
| 50 - <80 mL/min |
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| > 80 mL/min |
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