E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aortic valve stenosis |
Aortaklapstenose |
|
E.1.1.1 | Medical condition in easily understood language |
Stenosis of the aortic valve |
Forsnævring af aortaklappen |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002918 |
E.1.2 | Term | Aortic valve stenosis |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
To show that anticoagulation will provide better protection for patients after aortic valve replacement than platelet inhibition with Aspirin |
At vise at antikoagulationsmedicin vil yde bedre beskyttelse for patienter efter udskiftelse af aortaklappen end blodpladeinhibering med Aspirin. |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
Ikke relevant |
|
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 |
|
E.3 | Principal inclusion criteria |
1. Patients 18 years scheduled for surgical bioprosthetic aortic valve replacement. 2. Ability to understand the study background, risk and benefit of treatment and to give written informed consent 3. Scheduled for routine antithrombotic treatment after surgical valve replacement. Patient required to receive aspirin due to simultaneous by-pass operation are allowed in the study - to receive either aspirin along or rivaroxaban in addition to aspirin. |
1. Patienter 18 år, som i forvejen er indstillet til kirurgisk udskiftning af biologisk aorta klap 2. Kan forstå baggrunden for forsøget, risici og fordele ved behandlingen samt kan afgive skrifteligt informeret samtykke 3. Planlagt rutinebehandling mod blodpropper efter kirurgisk udskiftning af aortaklappen. Patienter som skal modtage Aspirin på grund af samtidig by-pass operation kan godt indgå i dette forsøg og vil enten få Aspirin alene eller Rivaroxaban samtidig med Aspirin. |
|
E.4 | Principal exclusion criteria |
1. Ongoing treatment with oral anticoagulants (warfarin, phenprocoumon or thrombin/factorXa oral anticoagulants). 2. Indication for oral anticoagulation treatment even if currently not treated (e.g. chronic atrial fibrillation, recent deep vein thrombosis, recent pulmonary embolism) 3. Indication for dual antiplatelet therapy (e.g. aspirin and ADP receptor inhibitor) 4. Known intolerance to aspirin or rivaroxaban. 5. Stroke within 6 months of study start. 6. Concomitant therapy with systemic drugs that are strong inhibitors of both CYP 3A4 and P-gp (azole antimycotics such as ketoconazole and itraconazole or HIV protease inhibitors such as ritonavir) 7. Concomitant therapy with drugs that are strong CYP 3A4 inducers (e.g. carbamazepine, phenytoin, rifampin, St. John’s wort) 8. Platelet count of less than 90,000 per cubic millimeter 9. Preoperative anemia with hemoglobin <6mmol/l 10. Creatinine clearance (Cockroft formula) <15 ml/min 11. Clinically significant gastrointestinal bleeding within 3 months 12. Previous intracranial hemorrhage; 13. The presence of a severe or active bleeding disorder. 14. Non-adherence to medications 15. Pregnancy or risk of pregnancy. In women of childbearing age, an approved birth control must be ensured. |
1. Varig oral behandling mod blodpropper (Warfarin, Phenoprocoumon eller thrombin/faktorXa orale blodprop behandlinger) 2. Indikation for oral blodprop behandling selvom vedkommende ikke umiddelbart er i behandling (f.eks. kronisk atrieflimren, nylig dyb vene blodprop, nylig lungeemboli) 3. Indikation for behandling mod blodpropper med to forskellige typer medicin (f.eks. Aspirin og ADP receptor hæmmer) 4. Kendt overfølsomhed over for Aspirin eller Rivaroxaban 5. Slagtilfælde indenfor 6 måneder før studiestart 6. Samtidig behandling med systemisk medicin som virker stærkt hæmmende på både leverenzymet CYP 3A4 samt af et protein, der primært findes i tarmene (P-gp) 7. Samtidig behandling med medicin, som virker stærkt fremmende på leverenzymet CYP 3A4 (f.eks. Carbamazepin, Phenytoin, Rifampin og Perikon) 8. Blodpladetælling på mindre end 90.000 pr. kubik millimeter 9. Blodmangel før operation med hæmoglobin <6 mmol/l 10. Kreatininclearance (nyrernes evne til at filtrere blodet for affaldsstoffer) (Cockroft formel) <15 ml/min 11. Klinisk signifikant mave-tarm blødning indenfor de sidste 3 måneder 12. Tidligere hjerneblødning 13. Tilstedeværelse af alvorlig eller aktiv blødningsforstyrrelse 14. At man ikke tager medicinen som anvist af lægen 15. Graviditet eller risiko for graviditet. Hos kvinder i den fødedygtige alder skal godkendt prævention benyttes |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is a combination of all-cause mortality, hospital admission for stroke and hospital admission for myocardial infarction. |
De primære endepunkter er en kombination af død uanset årsag, hospitalisering efter slagtilfælde og hospitalisering af myokardieinfarkt. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after randomization |
6 måneder efter randomisering |
|
E.5.2 | Secondary end point(s) |
Fatal or non-fatal arterial thrombotic event (myocardial infarction, stroke, peripheral arterial embolism). Cardiovascular mortality |
Dødelig eller ikke-dødelig arterial trombose (myokardieinfarkt, slagtilfælde, perifer arteriel emboli). Kardiovaskulær død. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 years after randomization |
2 år efter randomisering |
|
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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
End of trial will be 2 years after the last subject have been randomized |
Afslutning af forsøget vil være 2 år efter den sidste forsøgsperson er blevet randomiseret |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |