E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Splanchnic vein thrombosis (SVT) is an unusual site manifestation of venous thromboembolism (VTE). It includes the Budd-Chiari syndrome (BCS), portal vein thrombosis (PVT), mesenteric vein thrombosis (MVT) and splenic vein thrombosis (spVT). PVT is the most frequent manifestation of SVT, followed by MVT.
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Splanchische veneuze trombose (SVT) is wat locatie betreft een ongewoonlijke manifestatie van veneuze trombo-embolie (VTE). Het bevat de Budd-Chiari syndrome, vena porta trombose, vena mesenterica trombose en vena lienalis/splenica trombose. |
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E.1.1.1 | Medical condition in easily understood language |
The condition called splanchnic vein thrombosis (SVT) which causes decreased blood flow through one of your splanchnic veins (portal, mesenteric, or splenic vein). d.
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Bij splanchnische veneuze trombose wordt obstructie veroorzaakt in 1 van de aderen van het maagdarmstelsel, hierdoor kan het zuurstofarme bloed niet meer goed verder kan stromen.
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In this prospective cohort study, patients presenting with acute SVT will receive rivaroxaban 15 mg bid for 3 weeks followed by rivaroxaban 20 mg once daily for a total of 3 months. The primary safety and efficacy outcomes will be measured at 3 months. |
Om de veiligheid en effectiviteit van rivaroxaban 20mg 1dd1 gedurende een 3-maand behandeling voor splanchnische veneuze trombose te evalueren.
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Niet van toepassing |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
4.1 Inclusion criteria: 1. Patients aged 18 years or older 2. First episode of symptomatic, objectively diagnosed PVT, MVT, or spVT (diagnosed by CT, MRI and/or Doppler ultrasound). 3. Signed informed consent. |
1. Patiënten 18 jaar of ouder 2. Eerste episode van symptomatische, objectief gediagnosticeerde vena porta trombose (PVT), mesenterica trombose (MVT) of splenische trombose (spVT) (gediagnosticeerd via CT, MRI en/of Doppler echo) 3. Getekend informed consent |
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E.4 | Principal exclusion criteria |
1. Known liver cirrhosis (biopsy proven or with clinical, laboratory, or imaging evidence of chronic liver disease, within a context of chronic alcoholism, viral hepatitis, autoimmunity, Wilson's disease, iron overload) 2. Alanine aminotransferase level that is three times the upper limit of the normal range or higher 3. Budd-Chiari syndrome 4. Previous or ongoing variceal bleeding 5. Presence of portal vein cavernoma at the time of diagnosis 6. Anticipated abdominal surgical procedure 7. Known bleeding diathesis 8. Platelet count <100.000 mm3 9. Creatinine clearance <30 mL/min (Cockroft-Gault formula) 10. Life expectancy of less than 3 months 11. Expected inability to take oral medications 12. Concomitant treatment with azole antimycotics and human immunodeficiency virus protease inhibitors 13. Treatment with therapeutic doses of LMWH or UFH for more than 7 days 14. Ongoing treatment with VKA 15. Pregnancy or lactation. Note: Women of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy throughout the study. Acceptable methods of contraception include tubal ligation, oral contraceptive, barrier methods (intra-uterine device, diaphragm, femalecondom, male condom). Abstinence is an acceptable form of contraception, only insofar as patients agree to use another acceptable method of birth control, preferably a barrier method, if they become sexually active |
1. Bekende levercirrose 2. ALAT waarde > 3 keer hoger dan bovenste grens van normaalwaarde 3. Budd-Chiari syndrome 4. Eerdere of ongoing varices bloeding 5. Aanwezigheid van vena porta cavernoma ten tijde van diagnose 6. Geanticipeerde abdominale chirurgische procedure 7. Bekende versterkte bloedingsneiging 8. Trombocyten aantal <100 10^9/L 9. Kreatinine klaring < 30 ml/min (COckroft-Gault formule) 10. Levensverwachting minder dan 3 maanden 11. Verwachte onmogelijkheid inname orale medicatie 12. Gelijktijdige behandeling met azole antimycotica en HIV protease inhibitoren 13. Behandeling met therapeutische dosering LMWH of UFH voor meer dan 7 dagen 14. Lopende behandeling met vitamine K antagonisten (VKA) 15. Zwangerschap of het geven van borstvoeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome of the study is the occurrence of major bleeding events during the 3 months of active treatment and up to 2 days after the end of study treatment.
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Primaire onderzoeksvariabelen/uitkomstmaten: - major bleeding events gedurende de 3 maanden behandeling + tot 2 dagen nadat de behandeling is gestaakt
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 3 - Month 2 - Month 6 |
Week 3 - 2 maand - 6 maand |
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E.5.2 | Secondary end point(s) |
Secondary outcomes include:
o Mortality (overall and SVT related); o Clinically relevant, non-major bleeding occurred during the 3 months of active treatment and up to 2 days after the end of study treatment; o Detection of alanine aminotransferase levels of three times the upper limit of the normal range or higher with or without bilirubin levels of two times the upper limit of the normal range or higher during follow-up; o Patency of the portal vein trunk and at least one of its main right or left branches and patency of the superior and inferior mesenteric veins and of the splenic veins, defined as the normal appearance of a previously obstructed segment (as opposed to “obstruction”, defined as the presence of solid material in the vascular lumen); o Recurrent SVT, defined as thrombus extension or occurrence in a previously patent segment; o Symptomatic VTE in other sites, as diagnosed by appropriate imaging tests according to the site of thrombosis; o Mesenteric infarction as evidenced by a pathology specimen. |
Secundaire onderzoeksvariabelen/uitkomstmaten (indien van toepassing): Klik voor meer informatie - mortaliteit (overall en SVT gerelateerd) - klinisch relevante non-major bleeding events gedurende de 3 maanden behandeling + tot 2 dagen nadat de behandeling is gestaakt - detectie van alanine aminotransferase waarden van 3 x hoger dan de bovesnte grens van de normaal waarde gedurende follow up - doorgankelijkheid van de trunk van de vena porta en minstens 1 van de hoofdtakken links of rechts. Doorgankelijkheid van de superior en inferior mesenterica bemem em van de vena lienalis. Gedefinieerd als normale verschijning van een eerder geobstrueerd segment. - recidief SVT, gedefinieerd als trombus uitbreiding of event in een eerder doorgankelijk segment - symptomatische VTE op andere locaties (gediagnosticeerd door gepaste beeldvormende technieken) - mesenterisch infarct (op basis van pathologie) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Same as primary endpoints |
Zelfde als primaire eindpunten |
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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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Canada |
France |
Germany |
Italy |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |