Venous Thromboembolism
Conditions
Keywords
Pediatric
Brief summary
The purpose of this study is to evaluate comparative efficacy and safety of rivaroxaban to standard of care in children with acute venous thromboembolism.
Interventions
DRUGRivaroxaban (Xarelto, BAY59-7939)
Age and body weight-adjusted dosing equivalent to 20 mg rivaroxaban in adults, once daily or twice daily, as tablets
DRUGStandard of Care
LMWH (low molecular weight heparin) or fondaparinux or vitamin K antagonist (VKA) therapy. dose : as per standard of care
Sponsors
Janssen Research & Development, LLC
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Children aged birth to \< 18 years with confirmed venous thromboembolism who receive initial treatment with therapeutic dosages of UFH (unfractionated heparin), LMWH (low molecular weight heparin) or fondaparinux and require anticoagulant therapy for at least 90 days. However, children aged birth to \< 2 years with catheter-related thrombosis require anticoagulant therapy for at least 30 days. * For children younger than 6 months: * Gestational age at birth of at least 37 weeks. * Oral feeding/nasogastric/gastric feeding for at least 10 days. * Body weight ≥2600 g
Exclusion criteria
* Active bleeding or bleeding risk contraindicating anticoagulant therapy * An estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\*2 (in children younger than 1 year, serum creatinine results above 97.5th percentile excludes participation) * Hepatic disease which is associated with either: coagulopathy leading to a clinically relevant bleeding risk, or ALT\> 5x upper level of normal (ULN) or total bilirubin \> 2x ULN with direct bilirubin \> 20% of the total * Platelet count \< 50 x 109/L * Sustained uncontrolled hypertension defined as \> 95th age percentile * Life expectancy \< 3 months * Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), including but not limited to all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically * Concomitant use of strong inducers of CYP3A4, including but not limited to rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine * Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | During the main study treatment period (i.e., 3 months, except for children with central venous catheter venous thromboembolism (CVC-VTE) aged <2 years for whom it was 1 month) | The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population |
| Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | During extended treatment period: up to month 12. | Incidence rates for all children except those aged \< 2 years with catheter-related thrombosis. If no participant in the specific subgroup entered in the specific optional extension period, no analysis of an outcome was possible., The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference Population. |
| Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | More than 2 and up to 30 days after stop of study medication | The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported. |
| Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month) | The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization). |
| Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | During extended treatment period: up to month 12. | Incidence rates for all children except those aged \< 2 years with catheter-related thrombosis. If no participant entered in the specific optional extension period, no analysis of an outcome was possible. The CIAC classified bleeding as: Major bleeding defined as overt bleeding and: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 | 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. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 | 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. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 | 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. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 | 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. 'NA' denotes the data that cannot be calculated. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 | 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. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 | 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. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60 | 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. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated. |
| Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60 | 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. 'NA' denotes the data that cannot be calculated. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. |
| Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. |
| Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. |
| Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. |
| Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. |
| Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated. |
| Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, and up to 16 hours on Day 90 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated. |
| Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, up to 16 hours on Day 90 and follow-up up to 30 days | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated. |
| Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60 | This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. |
| Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60 | The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated. |
| Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month) | The secondary efficacy outcome defined as the composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging as assessed by central independent adjudication committee. (CIAC) Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population |
| AUC(0-24)ss in Plasma | over 24 hours | AUC(0-24)ss: Area under the concentration vs. time curve from time 0 to 24 hours at steady state. |
| Cmax,ss in Plasma | 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state) | Maximum drug concentration in measured matrix at steady state during a dosage interval |
| Ctrough,ss in Plasma | 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state) | Ctrough,ss refers to the drug concentration at the end of the dosage interval at steady state |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Finland, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Russia, Singapore, Slovakia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at 109 study centers in 28 countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Finland, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Russia, Singapore, Slovakia, Spain, Sweden, Switzerland, Turkey, UK, and USA between 13 Nov 2014 and 30 Jan 2019.
Pre-assignment details
A total of 520 children were screened for this study. Twenty children did not pass the screen of inclusion/exclusion criteria. A total of 500 children were randomized 2:1 to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban, Aged 12-<18 Children aged 12-\<18 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. | 184 |
| Rivaroxaban, Aged 6-<12 Children aged 6-\<12 years randomized to rivaroxaban received either tablet or oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of \< 20 kg received rivaroxaban as oral suspension. | 67 |
| Rivaroxaban, Aged 2-<6 Children aged 2-\<6 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of ≥ 20 kg received rivaroxaban tablets or oral suspension. Children with body weight of \< 20 kg received rivaroxaban as oral suspension. | 47 |
| Rivaroxaban, Aged 0.5-<2 Children aged 0.5-\<2 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of \< 20 kg received rivaroxaban as oral suspension. | 21 |
| Rivaroxaban, Aged Birth-<0.5 Children aged birth-\<0.5 years randomized to rivaroxaban received oral suspension after at least 5 days administration of initial therapy with UFH/LMWH/fondaparinux . Children with body weight of \< 20 kg received rivaroxaban as oral suspension. | 16 |
| Comparator, Aged 12-<18 Children aged 12-\<18 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. | 92 |
| Comparator, Aged 6-<12 Children aged 6-\<12 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. | 34 |
| Comparator, Aged 2-<6 Children aged 2-\<6 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. | 22 |
| Comparator, Aged 0.5-<2 Children aged 0.5-\<2 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. | 9 |
| Comparator, Aged Birth-<0.5 Children aged birth-\<0.5 years randomized to the comparator group continued with unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux or may switch to VKA therapy. VKA dosages were adjusted to maintain the INR within the therapeutic range (target 2.5, range 2.0 - 3.0). UFH, LMWH or fondaparinux could be discontinued once the INR was above 2.0 on two separate occasions, 24 hours apart. | 8 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 | 1 | 3 | 2 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Efficacy outcome reached | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Non-compliance with study drug | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Patient convenience | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 4 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Recovery | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 1 | 0 | 0 | 7 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Rivaroxaban, Aged 12-<18 | Rivaroxaban, Aged 6-<12 | Rivaroxaban, Aged 2-<6 | Rivaroxaban, Aged 0.5-<2 | Rivaroxaban, Aged Birth-<0.5 | Comparator, Aged 12-<18 | Comparator, Aged 6-<12 | Comparator, Aged 2-<6 | Comparator, Aged 0.5-<2 | Comparator, Aged Birth-<0.5 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 0.5-<2 years | 0 Participants | 0 Participants | 0 Participants | 21 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants | 0 Participants | 30 Participants |
| Age, Customized 12-<18 years | 184 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 92 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 276 Participants |
| Age, Customized 2-<6 years | 0 Participants | 0 Participants | 47 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 22 Participants | 0 Participants | 0 Participants | 69 Participants |
| Age, Customized 6-<12 years | 0 Participants | 67 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 34 Participants | 0 Participants | 0 Participants | 0 Participants | 101 Participants |
| Age, Customized Birth-<0.5 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 164 Participants | 58 Participants | 42 Participants | 15 Participants | 12 Participants | 79 Participants | 26 Participants | 19 Participants | 8 Participants | 6 Participants | 429 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 7 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 42 Participants |
| Sex: Female, Male Female | 97 Participants | 24 Participants | 24 Participants | 10 Participants | 5 Participants | 55 Participants | 15 Participants | 9 Participants | 5 Participants | 1 Participants | 245 Participants |
| Sex: Female, Male Male | 87 Participants | 43 Participants | 23 Participants | 11 Participants | 11 Participants | 37 Participants | 19 Participants | 13 Participants | 4 Participants | 7 Participants | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 162 | 2 / 329 |
| other Total, other adverse events | 121 / 162 | 275 / 329 |
| serious Total, serious adverse events | 35 / 162 | 78 / 329 |
Outcome results
Primary
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period
Incidence rates for all children except those aged \< 2 years with catheter-related thrombosis. If no participant in the specific subgroup entered in the specific optional extension period, no analysis of an outcome was possible., The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference Population.
Time frame: During extended treatment period: up to month 12.
Population: Full analysis set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 2.6 Percentage of participants |
| Rivaroxaban Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Rivaroxaban Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 5.3 Percentage of participants |
| Comparator Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 2.2 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 12-<18 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 6-<12 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 6-<12 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator, Aged 6-<12 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Comparator, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged Birth-<0.5 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
Primary
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 2.2 Percentage of participants | 95% Confidence Interval 0.7 |
| Comparator Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged 12-<18 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 3.3 Percentage of participants | 95% Confidence Interval 0.9 |
| Comparator, Aged 6-<12 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 2.9 Percentage of participants | 95% Confidence Interval 0.2 |
| Comparator, Aged 2-<6 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 4.5 Percentage of participants | 95% Confidence Interval 0.2 |
| Comparator, Aged 0.5-<2 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged Birth-<0.5 | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
Primary
Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period
The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time frame: During the main study treatment period (i.e., 3 months, except for children with central venous catheter venous thromboembolism (CVC-VTE) aged <2 years for whom it was 1 month)
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 1.2 Percentage of participants |
| Comparator Group | Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period | 3.0 Percentage of participants |
p-value: 0.150995% CI: [0.11, 1.41]Expl. Cox Proportional Hazards Model
Primary
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period
Incidence rates for all children except those aged \< 2 years with catheter-related thrombosis. If no participant entered in the specific optional extension period, no analysis of an outcome was possible. The CIAC classified bleeding as: Major bleeding defined as overt bleeding and: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life.
Time frame: During extended treatment period: up to month 12.
Population: Safety analysis set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rivaroxaban Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 2.6 Percentage of participants |
| Rivaroxaban Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 1.1 Percentage of participants |
| Rivaroxaban Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 5.3 Percentage of participants |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 12-<18 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 12-<18 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Comparator, Aged 12-<18 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator, Aged 6-<12 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Comparator, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 2 (month 6 to 9) | 0.0 Percentage of participants |
| Comparator, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 3 (month 9 to 12) | 0.0 Percentage of participants |
| Comparator, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
| Comparator, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period | Extension 1 (month 3 to 6) | 0.0 Percentage of participants |
Primary
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period
The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization).
Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Population: Safety analysis set (SAF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivaroxaban Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 3 Percentage of participants |
| Comparator Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 1.9 Percentage of participants |
Primary
Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period
The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization).
Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Population: Safety analysis set (SAF)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 1.7 Percentage of participants | 95% Confidence Interval 0.5 |
| Comparator Group | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 3.0 Percentage of participants | 95% Confidence Interval 0.5 |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 6.5 Percentage of participants | 95% Confidence Interval 1.8 |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 4.8 Percentage of participants | 95% Confidence Interval 0.2 |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 6.7 Percentage of participants | 95% Confidence Interval 0.3 |
| Comparator, Aged 12-<18 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 2.2 Percentage of participants | 95% Confidence Interval 0.4 |
| Comparator, Aged 6-<12 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged 2-<6 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged 0.5-<2 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 11.1 Percentage of participants | 95% Confidence Interval 0.6 |
| Comparator, Aged Birth-<0.5 | Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
Primary
Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication)
The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported.
Time frame: More than 2 and up to 30 days after stop of study medication
Population: Full analysis set (FAS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rivaroxaban Group | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator Group | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 2 Participants |
| Rivaroxaban, Aged 2-<6 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Rivaroxaban, Aged 0.5-<2 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Rivaroxaban, Aged Birth-<0.5 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator, Aged 12-<18 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator, Aged 6-<12 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator, Aged 2-<6 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator, Aged 0.5-<2 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
| Comparator, Aged Birth-<0.5 | Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication) | 0 Participants |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (0.5-1.5h) n=154 | 1.17 ratio | Standard Deviation 0.28 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (2.5-4h) n=149 | 1.38 ratio | Standard Deviation 0.5 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 60 (2-8h) n=153 | 1.33 ratio | Standard Deviation 0.38 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=17 | 1.27 ratio | Standard Deviation 0.2 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=17 | 1.39 ratio | Standard Deviation 0.26 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=19 | 1.24 ratio | Standard Deviation 0.2 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-3h) n=9 | 1.20 ratio | Standard Deviation 0.39 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 60 (2-6h) n=6 | 1.10 ratio | Standard Deviation 0.47 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (0.5-3h) n=4 | 1.50 ratio | Standard Deviation 0.83 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-6h) n=4 | 1.13 ratio | Standard Deviation 0.06 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 30 (0.5-3h) n=9 | 1.31 ratio | Standard Deviation 0.15 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 60 (2-6h) n=3 | 1.21 ratio | Standard Deviation 0.16 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=31 | 1.18 ratio | Standard Deviation 0.24 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=30 | 1.11 ratio | Standard Deviation 0.24 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=30 | 1.15 ratio | Standard Deviation 0.22 |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (2.5-4h) n=1 | 1.13 ratio | — |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 60 (2-8h) n=2 | 1.10 ratio | Standard Deviation 0.02 |
| Unknown | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-1.5h) n=0 | — ratio | — |
Secondary
Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
The aPTT is a screening test for the intrinsic pathway and is sensitive for deficiencies of Factors I, II, V,VIII, IX, X, XI and XII. The initial read-out is in seconds. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (0.5-1.5h) n=1 | 0.90 ratio | — |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (2.5-4h) n=32 | 1.29 ratio | Standard Deviation 0.33 |
| Rivaroxaban Group | Activated Partial Thromboplastin Time (aPTT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-8h) n=29 | 1.23 ratio | Standard Deviation 0.21 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time frame: Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (0.5-1.5h) n=141 | 164.46 microgram per liter (mcg/L) | Standard Deviation 124.46 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (2.5-4h) n=164 | 254.66 microgram per liter (mcg/L) | Standard Deviation 188.64 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 60 (2-8h) n=167 | 255.40 microgram per liter (mcg/L) | Standard Deviation 171.59 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 90 (20-24h) n=58 | 62.12 microgram per liter (mcg/L) | Standard Deviation 175.87 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time frame: Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 24 hours on Day 90
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=22 | 206.89 microgram per liter (mcg/L) | Standard Deviation 105.01 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=23 | 263.24 microgram per liter (mcg/L) | Standard Deviation 156.73 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=22 | 243.45 microgram per liter (mcg/L) | Standard Deviation 124.92 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 90 (20-24h) n=9 | 27.39 microgram per liter (mcg/L) | Standard Deviation 14.66 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, up to 16 hours on Day 90 and follow-up up to 30 days
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-3h) n=12 | 111.35 microgram per liter (mcg/L) | Standard Deviation 97.03 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (2-6h) n=11 | 147.24 microgram per liter (mcg/L) | Standard Deviation 125.4 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 90 (10-16h) n=3 | 23.40 microgram per liter (mcg/L) | Standard Deviation 4.51 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Follow-up n=1 | 71.30 microgram per liter (mcg/L) | — |
Secondary
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 3 hours post dose on Day 30, up to 6 hours post dose on Day 60, and up to 16 hours on Day 90
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 90 (10-16h) n=1 | 62.56 microgram per liter (mcg/L) | — |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (0.5-3h) n=4 | 209.67 microgram per liter (mcg/L) | Standard Deviation 127.86 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-6h) n=4 | 140.46 microgram per liter (mcg/L) | Standard Deviation 78.82 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time frame: Up to 3 hours post dose on Day 30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 30 (0.5-3h) n=10 | 118.12 microgram per liter (mcg/L) | Standard Deviation 82.08 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 60 (2-6h) n=5 | 228.03 microgram per liter (mcg/L) | Standard Deviation 181.08 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time frame: Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=35 | 126.53 microgram per liter (mcg/L) | Standard Deviation 81.78 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 90 (10-16h) n=20 | 47.49 microgram per liter (mcg/L) | Standard Deviation 66.88 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=37 | 96.82 microgram per liter (mcg/L) | Standard Deviation 76.77 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=36 | 139.10 microgram per liter (mcg/L) | Standard Deviation 102.19 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 4 hours post dose on Day 30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-1.5h) n=1 | 247.54 microgram per liter (mcg/L) | — |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (2.5-4h) n=2 | 160.71 microgram per liter (mcg/L) | Standard Deviation 153.84 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 60 (2-8h) n=4 | 121.09 microgram per liter (mcg/L) | Standard Deviation 81.94 |
Secondary
Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
This is a method for measuring the inhibition of Factor Xa activity determined by an ex vivo using a photometric method.
Time frame: Up to 4 hours post dose on Day 30, up to 8 hours post dose on Day 60, and up to 16 hours on Day 90
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (2.5-4h) n=37 | 177.78 microgram per liter (mcg/L) | Standard Deviation 147.29 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-8h) n=36 | 150.03 microgram per liter (mcg/L) | Standard Deviation 95.77 |
| Rivaroxaban Group | Anti-Xa Values: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 90 (10-16h) n=18 | 54.40 microgram per liter (mcg/L) | Standard Deviation 51.52 |
Secondary
AUC(0-24)ss in Plasma
AUC(0-24)ss: Area under the concentration vs. time curve from time 0 to 24 hours at steady state.
Time frame: over 24 hours
Population: Pharmacokinetics analysis set (PKS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | AUC(0-24)ss in Plasma | 2120 microgram*hour per liter | Geometric Coefficient of Variation 26.4 |
| Comparator Group | AUC(0-24)ss in Plasma | 1960 microgram*hour per liter | Geometric Coefficient of Variation 31.7 |
| Rivaroxaban, Aged 2-<6 | AUC(0-24)ss in Plasma | 2380 microgram*hour per liter | Geometric Coefficient of Variation 40.7 |
| Rivaroxaban, Aged 0.5-<2 | AUC(0-24)ss in Plasma | 1840 microgram*hour per liter | Geometric Coefficient of Variation 36.4 |
| Rivaroxaban, Aged Birth-<0.5 | AUC(0-24)ss in Plasma | 1590 microgram*hour per liter | Geometric Coefficient of Variation 29.6 |
Secondary
Cmax,ss in Plasma
Maximum drug concentration in measured matrix at steady state during a dosage interval
Time frame: 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours (one dosing interval in steady state)
Population: Pharmacokinetics analysis set (PKS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | Cmax,ss in Plasma | 237 microgram per liter | Geometric Coefficient of Variation 20.6 |
| Comparator Group | Cmax,ss in Plasma | 184 microgram per liter | Geometric Coefficient of Variation 36.2 |
| Rivaroxaban, Aged 2-<6 | Cmax,ss in Plasma | 182 microgram per liter | Geometric Coefficient of Variation 31.2 |
| Rivaroxaban, Aged 0.5-<2 | Cmax,ss in Plasma | 136 microgram per liter | Geometric Coefficient of Variation 29.4 |
| Rivaroxaban, Aged Birth-<0.5 | Cmax,ss in Plasma | 119 microgram per liter | Geometric Coefficient of Variation 24.1 |
Secondary
Ctrough,ss in Plasma
Ctrough,ss refers to the drug concentration at the end of the dosage interval at steady state
Time frame: 0 hours to 24 hours, 0 hours to 12 hours or 0 hours to 8 hours(one sampling interval in steady state)
Population: Pharmacokinetics analysis set (PKS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | Ctrough,ss in Plasma | 20.7 microgram per liter | Geometric Coefficient of Variation 45.8 |
| Comparator Group | Ctrough,ss in Plasma | 21.4 microgram per liter | Geometric Coefficient of Variation 62.7 |
| Rivaroxaban, Aged 2-<6 | Ctrough,ss in Plasma | 31.6 microgram per liter | Geometric Coefficient of Variation 70.1 |
| Rivaroxaban, Aged 0.5-<2 | Ctrough,ss in Plasma | 22.9 microgram per liter | Geometric Coefficient of Variation 68.6 |
| Rivaroxaban, Aged Birth-<0.5 | Ctrough,ss in Plasma | 18.5 microgram per liter | Geometric Coefficient of Variation 50.4 |
Secondary
Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period
The secondary efficacy outcome defined as the composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration on repeat imaging as assessed by central independent adjudication committee. (CIAC) Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population
Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)
Population: Full analysis set (FAS)
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Rivaroxaban Group | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 2.2 Percentage of participants | 95% Confidence Interval 0.7 |
| Comparator Group | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Rivaroxaban, Aged 2-<6 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 2.1 Percentage of participants | 95% Confidence Interval 0.1 |
| Rivaroxaban, Aged 0.5-<2 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Rivaroxaban, Aged Birth-<0.5 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged 12-<18 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 4.3 Percentage of participants | 95% Confidence Interval 1.5 |
| Comparator, Aged 6-<12 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 2.9 Percentage of participants | 95% Confidence Interval 0.2 |
| Comparator, Aged 2-<6 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 4.5 Percentage of participants | 95% Confidence Interval 0.2 |
| Comparator, Aged 0.5-<2 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
| Comparator, Aged Birth-<0.5 | Incidence Rates of the Composite of All Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging During the Main Treatment Period | 0.0 Percentage of participants | 95% Confidence Interval 0 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years
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.
Time frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (2.5-4h) n=150 | 1.57 ratio | Standard Deviation 0.36 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 60 (2-8h) n=156 | 1.52 ratio | Standard Deviation 0.29 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 12-<18 Years | Day 30 (0.5-1.5h) n=156 | 1.29 ratio | Standard Deviation 0.28 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years
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.
Time frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=18 | 1.46 ratio | Standard Deviation 0.25 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=20 | 1.67 ratio | Standard Deviation 0.39 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Once Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=20 | 1.52 ratio | Standard Deviation 0.33 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years
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.
Time frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-3h) n=9 | 1.25 ratios | Standard Deviation 0.18 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 0.5-<2 Years | Day 60 (2-6h) n=7 | 2.00 ratios | Standard Deviation 2.22 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years
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.
Time frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (0.5-3h) n=4 | 1.87 ratio | Standard Deviation 1.09 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-6h) n=4 | 1.32 ratio | Standard Deviation 0.12 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years
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.
Time frame: Up to 3 hours post dose on Day30, and up to 6 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 30 (0.5-3h) n=11 | 1.35 ratio | Standard Deviation 0.2 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Three Times Daily (Suspension) in the Age Group Birth-<0.5 Years | Day 60 (2-6h) n=4 | 1.45 ratio | Standard Deviation 0.16 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years
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.
Time frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 60 (2-8h) n=34 | 1.21 ratio | Standard Deviation 0.19 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (0.5-1.5h) n=33 | 1.17 ratio | Standard Deviation 0.23 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension and Tablet) in the Age Group 6-<12 Years | Day 30 (2.5-4h) n=33 | 1.26 ratio | Standard Deviation 0.22 |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years
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. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (2.5-4h) n=1 | 1.41 ratio | — |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 60 (2-8h) n=2 | 1.05 ratio | Standard Deviation 0.17 |
| Unknown | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 0.5-<2 Years | Day 30 (0.5-1.5h) n=0 | — ratio | — |
Secondary
Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years
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. 'NA' denotes the data that cannot be calculated.
Time frame: Up to 4 hours post dose on Day30, and up to 8 hours post dose on Day 60
Population: Participants in pharmacodynamics set (PDS) were analyzed for this endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (2.5-4h) n=34 | 1.36 ratio | Standard Deviation 0.28 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 60 (2-8h) n=32 | 1.33 ratio | Standard Deviation 0.26 |
| Rivaroxaban Group | Prothrombin Time (PT) Ratios to Baseline: Rivaroxaban Administered Twice Daily (Suspension) in the Age Group 2-<6 Years | Day 30 (0.5-1.5h) n=1 | 0.99 ratio | — |