Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37720   clinical trials with a EudraCT protocol, of which   6181   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2006-004595-13
    Sponsor's Protocol Code Number:BAY59-7939/11630
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-04-03
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2006-004595-13
    A.3Full title of the trial
    A Prospective, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Multicenter, Event-Driven, Non-Inferiority Study Comparing the Efficacy and Safety of Once-Daily Oral Rivaroxaban (BAY 59-7939) with Adjusted-Dose Oral Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Subjects With Non-Valvular Atrial Fibrillation
    Studio multicentrico, prospettico, randomizzato, in doppio cieco, per gruppi paralleli, con doppio placebo, event-driven, per dimostrare la non inferiorita` in termini di efficacia e sicurezza del rivaroxaban (BAY 59-7939) orale somministrato una volta al giorno rispetto al warfarin orale con aggiustamento della dose, nel trattamento preventivo dell'ictus e dell'embolia sistemica del sistema nervoso non centrale nei pazienti affetti da fibrillazione atriale non valvolare
    A.4.1Sponsor's protocol code numberBAY59-7939/11630
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBAYER
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namerivaroxaban
    D.3.2Product code NA
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNrivaroxaban
    D.3.9.1CAS number 366789-02-8
    D.3.9.2Current sponsor codeBAY 59-7939
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namerivaroxaban
    D.3.2Product code NA
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNrivaroxaban
    D.3.9.1CAS number 366789-02-8
    D.3.9.2Current sponsor codeBAY 59-7939
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namewarfarin
    D.3.2Product code NA
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNWarfarin
    D.3.9.1CAS number 129-06-6
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namewarfarin
    D.3.2Product code NA
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNWarfarin
    D.3.9.1CAS number 129-06-6
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namewarfarin
    D.3.2Product code NA
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNWarfarin
    D.3.9.1CAS number 129-06-6
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 5
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Prevention of Stroke and Non-CNS Systemic Embolism in Non-Valvular Atrial Fibrillation
    Prevenzione di ictus ed embolia sistemica del sistema nervoso non centrale in pazienti affetti da fibrillazione atriale non valvolare.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10003658
    E.1.2Term Atrial fibrillation
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to demonstrate that the efficacy of rivaroxaban, a direct FXa inhibitor, is non-inferior to that of dose-adjusted warfarin for the prevention of thromboembolic events in subjects with non-valvular atrial fibrillation as measured by the composite of stroke and non-central nervous system (non-CNS) systemic embolism. The principal safety objective of this study is to demonstrate that rivaroxaban is superior to dose-adjusted warfarin as assessed by the composite of major and non-major clinically relevant bleeding events.
    L'obiettivo principale dello studio e' dimostrare che l'efficacia del rivaroxaban, un inibitore diretto dell'FXa, e' non-inferiore a quella del warfarin con aggiustamento della dose nella terapia preventiva degli eventi tromboembolici indicata per i pazienti affetti da fibrillazione atriale non valvolare. L'efficacia sara' misurata in base all'endpoint composito di ictus ed embolia sistemica del sistema nervoso periferico. L'obiettivo principale relativo alla sicurezza e' dimostrare che il rivaroxaban e' superiore al warfarin con aggiustamento della dose. La sicurezza sara' misurata in base all'endpoint composito di eventi di sanguinamento maggiori ed eventi di sanguinamento minori clinicamente rilevanti.
    E.2.2Secondary objectives of the trial
    The major secondary efficacy objectives are to compare the effects of rivaroxaban and warfarin with respect to the composite of stroke, non-CNS systemic embolism, and vascular death and the composite of stroke, non-CNS systemic embolism, myocardial infarction, and vascular death. Other secondary efficacy objectives are to compare the effects of rivaroxaban and warfarin with respect to the individual components of the composite primary and major secondary endpoints, disabling stroke (modified Rankin Scale score of 3 to 5 inclusive), and all-cause mortality. Other safety objectives are to compare rivaroxaban and warfarin with respect to the individual bleeding event categories, adverse events, and clinical laboratory evaluations (including liver function tests LFTs]).
    Gli obiettivi secondari piu' rilevanti in relazione all'eff sono il confronto degli effetti del rivaroxaban e del warfarin rispetto all'endpoint composito di ictus,embolia sistemica del sistema nervoso non centrale e morte vascolare e all'endpoint composito di ictus,embolia sistemica del sistema nervoso non centrale,infarto miocardico e morte vascolare.Altri obiettivi secondari in relazione all'eff sono il confronto degli effetti del rivaroxaban e del warfarin rispetto ai singoli eventi compresi nell'endpoint composito principale e negli endpoint compositi secondari piu' rilevanti,all'ictus invalidante(punteggio della scala Rankin modificata da 3 a 5 compreso)e alla mortalita' per qualsiasi causa.Altri obiettivi in relazione alla sicurezza sono il confronto degli effetti del rivaroxaban e del warfarin rispetto alle singole categorie comprese negli eventi di sanguinamento,agli eventi indesiderati e alle valutazioni cliniche di laboratorio(compresi i test della funzione epatica [LFT]).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    ALTRI SOTTOSTUDI:
    Farmacogenomica

    E.3Principal inclusion criteria
    Men or women aged &#8805;18 years • Non-valvular atrial fibrillation documented by ECG on at least 2 occasions. One occasion must be between 1 to 6 months before the screening visit and the second within 14 days before randomization • History of prior ischemic stroke, TIA or non-CNS systemic embolism believed to be cardioembolic in origin or has 2 or more of the following risk factors: - Heart failure and/or left ventricular ejection fraction &#8804;35% - Hypertension (defined as use of antihypertensive medications within 6 months before the screening visit or persistent systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg) - Age &#8805;75 years - Diabetes mellitus (defined as a history of type 1 or type 2 diabetes mellitus or use of antidiabetic medications within 6 months before screening visit) • Female subjects must be postmenopausal (for at least 2 years), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, have a negative serum &#946;-hCG pregnancy test at screening. • Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study • In order to participate in the optional pharmacogenomic component, subjects must have signed the informed consent for DNA research document indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit)
    1.Maschi e femmine di eta' &#8805;18, che abbiano firmato il modulo di consenso informato, affetti da fibrillazione atriale senza disfunzione valvolare, a rischio di ictus e di embolie non a carico del sistema nervoso centrale.
    2.Saranno considerati idonei i pazienti precedentemente colpiti da ictus, TIA o embolia sistemica non a carico del sistema nervoso centrale, oppure i pazienti che presenteranno due o piu' di due dei seguenti fattori di rischio:
    •eta' &#8805; 75 anni,
    •ipertensione,
    •insufficienza cardiaca e/o frazione di eiezione ventricolare sinistra &#8804; 35%
    •diabete mellito.
    3.I soggetti di sesso femminile dovranno essere chirurgicamente sterili, non attive sessualmente, o, se attive sessualmente, praticare un efficace metodo di contraccezione prima dell'ammissione allo studio e durante lo stesso. Le donne in eta' fertile dovranno essere sottoposte a un test urinario di gravidanza (&#61538;-hCG) con esito negativo alla visita di screening. Ulteriori test di gravidanza sul siero o sulle urine potranno essere eseguiti nel corso dello studio se ritenuti necessari dallo sperimentatore o richieste dai dispositivi di legge locali, per escludere lo stato di gravidanza, e dovranno risultare negativi per consentire la permanenza della paziente nello studio.
    4.I soggetti dovranno specificatamente essere d'accordo di adeguarsi nel corso dello studio alla lista di terapie consentite e non consentite contenute nella Sezione 9 pag 52 del protocollo 'Concomitant Therapy'
    E.4Principal exclusion criteria
    Cardiac-Related Conditions • Hemodynamically significant mitral valve stenosis • Prosthetic heart valve • Planned cardioversion (electrical or pharmacological) • Transient atrial fibrillation caused by a reversible disorder (e.g., thyrotoxicosis, PE, recent surgery, MI) • Known presence of atrial myxoma or left ventricular thrombus • Active endocarditis Hemorrhage Risk-Related Criteria • Active internal bleeding • History of or condition associated with increased bleeding risk including, but not limited to: - Major surgical procedure or trauma within 30 days before the randomization visit - Clinically significant gastrointestinal bleeding within 6 months before the randomization visit - History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding - Chronic hemorrhagic disorder - Known intracranial neoplasm, arteriovenous malformation, or aneurysm • Planned invasive procedure with potential for uncontrolled bleeding, including major surgery • Platelet count <90,000/&#956;L at the screening visit • Sustained uncontrolled hypertension: systolic blood pressure &#8805;180 mmHg or diastolic blood pressure &#8805;100 mmHg Concomitant Conditions and Therapies • Severe, disabling stroke (modified Rankin score of 3 to 5, inclusive [Attachment 2]) within 6 months or any stroke within 30 days before the randomization visit • Transient ischemic attack within 3 days before the randomization visit Indication for anticoagulant therapy for a condition other than atrial fibrillation (e.g., VTE) • Concomitant treatment with an oral or intravenous antiplatelet agent or use within 5 days before randomization (except aspirin and thienopyridines as outlined in Section 9.0, Concomitant Therapy) or concomitant treatment with a fibrinolytic agent or use within 10 days of randomization • Anticipated need for chronic treatment with a non-steroidal anti-inflammatory drug • Treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease inhibitors, within 4 days before randomization, or planned treatment during the time period of the study • Anemia (hemoglobin <10 g/dL) at the screening visit • Pregnancy or breast feeding • Any other contraindication to warfarin • Known HIV infection at time of screening • Calculated CLCR <30 mL/min at the screening visit (refer to Attachment 4 for calculating CLCR) • Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis), or ALT >3 x the ULN Study Participation and Follow-up-Related Criteria: • Serious concomitant illness associated with a life expectancy of less than 2 years • Drug addiction or alcohol abuse within 3 years before the randomization visit • Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment • Previous randomization in the present study or other study of rivaroxaban • Known allergy or hypersensitivity to any component of rivaroxaban, warfarin or placebo excipients (includes lactose, microcrystalline cellulose, magnesium stearate, hypromellose, macrogol, croscarmellose sodium, sodium lauryl sulfate, titanium oxide/ferric oxide red, titanium dioxide/ferric oxide red, anhydrous lactose, pregelatinized starch, FD&C Red #6 barium lake, FD&C Yellow #10 aluminum lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, cornstarch, lactose monohydrate) • Inability or unwillingness to comply with study-related procedures • Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
    Di tipo generale
    1.Allergia nota a uno qualsiasi dei componenti (compresi gli eccipienti) delle compresse di rivaroxaban, warfarin o relative formulazioni placebo.
    2.Trattamento con un qualsiasi farmaco sperimentale o uso di qualsiasi dispositivo medico sperimentale entro i 30 giorni precedenti l'inizio del previsto trattamento di studio.
    3.Donne in stato di gravidanza o che allattano o che abbiano in programma l'inizio di una gravidanza durante il periodo previsto per la partecipazione allo studio.
    4.Donne in eta' fertile che non utilizzino adeguati metodi contraccettivi.
    5.Soggetti che abbiano in precedenza completato o siano usciti da questo studio o qualsiasi altro studio su rivaroxaban.
    6.Impiegati del centro di sperimentazione clinica o dello sperimentatore, persone coinvolte direttamente nello studio o in altri studi sotto la direzione dello sperimentatore o del centro di sperimentazione clinica, familiari degli impiegati o dello sperimentatore.
    Condizioni cardiache:
    1.Stenosi mitralica clinicamente significativa.
    2.Presenza di protesi valvolari cardiache.
    3.Cardioversione (sia elettrica che farmacologica) gia' programmata.
    4.Fibrillazione atriale transitoria causata da un disturbo reversibile (ad es.tireotossicosi, embolia polmonare, interventi chirurgici recenti, infarto miocardico).
    5.Presenza nota di mixoma atriale o trombo ventricolare sinistro.
    6.Endocardite attiva.
    Condizioni che possono aumentare il rischio emorragico.
    1.Emorragia interna in atto.
    2.Intervento chirurgico maggiore o trauma nei 30 giorni precedenti la visita di randomizzazione.
    3.Emorragia gastrointestinale clinicamente significativa n ei 6 mesi precedenti la visita di randomizzazione.
    4.Anamnesi di emorragia intracranica, intraoculare, spinale, o intraarticolare non traumatica.
    5.Malattie emorragiche croniche
    6.Neoplasia intracranica nota, malformazione arteriovenosa, o aneurisma.
    7.Procedure invasive gia' programmate (compresi interventi chirurgici maggiori) potenzialmente in grado di provocare fenomeni emorragici incontrollati.
    8.Conta piastrinica &lt; 90.000/&#61549;L alla visita di screening
    9.Ipertensione arteriosa non controllata protratta (pressione sistolica &gt;/= 180 mm Hg o pressione diastolica &gt;/= 100 mm Hg)
    10.Qualsiasi altra condizione nota per aumentare il rischio di emorragia.
    Condizioni concomitanti e terapie
    1.Ictus grave
    2.Attacco cerebrale ischemico transitorio (TIA) nei 3 gg.precedenti la visita di randomizzazione
    3.Indicazione alla terapia anticoagulante per qualsiasi condizione diversa dalla fibrillazione atriale (ad es.per tromboembolismo venoso).
    4.Trattamento concomitante o uso nei 5 gg.precedenti la visita di randomizzazione con/di farmaci antipiastrinici per via orale o endovenosa (ad ecc.di aspirina e derivati tienopiridinici - vd.Sez.9.0 del protocollo).
    5.Trattamento concomitante o uso nei 10 gg.precedenti la visita di randomizzazione con/di farmaci fibrinolitici.
    6.Prevista necessita' di trattamento cronico con farmaci antiinfiammatori (FANS)
    7.Trattamento con un forte inibitore del Citocromo P450 3A4 come come ketoconazolo o inibitori delle proteasi, praticato entro i 4 gg.precedenti la randomizzazione, o programmato nel periodo previsto per lo studio.
    8.Anemia (emoglobina &lt; 10 g/dL) alla visita di screening.
    9.Qualsiasi altra controindicazione al warfarin.
    10.Infezione nota da HIV alla visita di screening.
    11.Clearance della creatinina &lt; 30mL/min alla visita di screening.
    12.Epatopatia significativa nota (epatite acuta, epatite cronica attiva, cirrosi) o ALT &gt; 3 volte il limite superiore dell'intervallo di normalita'.
    13.Problemi per abuso di sostanze (droghe o alcool) nei 3 anni precedenti.
    14.Qualsiasi grave condizione che limiti l'attesa di vita a meno di 2 anni.
    15.Impossibita' o non volonta' di sottoporsi alle procedure sperimentali
    E.5 End points
    E.5.1Primary end point(s)
    The principal safety endpoint is the composite of major and non-major clinically relevant bleeding events.
    Il parametro principale relativo alla sicurezza e' rappresentato dall'endpoint composito di eventi di sanguinamento maggiori e minori clinicamente rilevanti
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    warfarin
    warfarin
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned39
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months48
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    donne in eta' fertile con adeguato sistema di contraccezione
    F.4 Planned number of subjects to be included
    F.4.1In the member state420
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 9000
    F.4.2.2In the whole clinical trial 14000
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2007-04-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-02-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-09-03
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA