E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of symptomatic venous thromboembolism (VTE) and VTE-related death posthospital discharge in high-risk, medically ill patients. |
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E.1.1.1 | Medical condition in easily understood language |
Prevent the occurrence of a blood clot inside a blood vessel that blocks the flow of blood through the circulatory system in patients who have been discharged from the hospital |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the efficacy and safety of rivaroxaban compared with placebo in the prevention of symptomatic venous thromboembolism (VTE: lower extremity deep vein thrombosis [DVT] and non-fatal pulmonary embolism [PE]) and VTE-related death (death due to PE or death in which PE cannot be ruled out as the cause) post-hospital discharge in high-risk, medically ill patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare rivaroxaban with placebo in the following post-hospital discharge outcomes in high-risk, medically ill patients:
- VTE-related death (death due to PE or death in which PE cannot be ruled out as the cause)
- Symptomatic VTE (lower extremity DVT and non-fatal PE)
- The composite of symptomatic VTE (lower extremity DVT and non-fatal PE) and all-cause mortality (ACM)
- The composite of symptomatic VTE (lower extremity DVT and non-fatal PE), MI, non-hemorrhagic stroke and CV death(death due to a known CV
cause and death in which a CV cause cannot be ruled out; by this definition, a VTE-related death is considered a CV death)
- ACM |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
As part of protocol RIVAROXDVT3002, an optional pharmacokinetic sub-study will be conducted for selected sites only. The objective of the sub-study is to assess the kinetics of rivaroxaban in high-risk, medically ill patients, to describe drug exposure based on CrCl. |
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E.3 | Principal inclusion criteria |
•The duration of the index hospitalization must have been at least 3 and no more than 10 consecutive days
•Must meet venous thromboembolism (VTE) risk criteria with a total modified Improve VTE Risk Score of: greater than or equal 4, or 3 with D-dimer > 2*upper limit of normal (ULN), or 2 with D-dimer > 2*ULN |
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E.4 | Principal exclusion criteria |
•Any serious bleeding within 3 months prior to randomization or occurring during index hospitalization
•Serious trauma within 4 weeks before randomization
•History of hemorrhagic stroke at any time in the past
•Severe head trauma within 4 weeks of randomization
•Any medical condition that requires chronic use of any parenteral or oral anticoagulation
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Time from randomization to the first occurrence of symptomatic venous thromboembolism event (VTE) and VTE-related death
2. Time from randomization to the first occurrence of major bleeding |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From day 1 up to Day 45
2. From day 1 up to Day 45 |
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E.5.2 | Secondary end point(s) |
1. Time from randomization to an occurrence of VTE related death
2. Time from randomization to the first occurrence of a symptomatic VTE
3. Time from randomization to the first occurrence of a composite of symptomatic VTE and all-cause mortality (ACM)
4. Time from randomization to an occurrence of ACM
5. Time from randomization to an occurrence of myocardial infarction
6. Time from randomization to an occurrence of non-hemorrhagic stroke
7. Time from randomization to an occurrence of cardiovascular death |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-7 - From day 1 up to Day 45 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 447 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belarus |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Canada |
Colombia |
Croatia |
Czech Republic |
Denmark |
Estonia |
Georgia |
Germany |
Greece |
Hungary |
Israel |
Italy |
Latvia |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Mexico |
Netherlands |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 23 |