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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2019-004975-37
    Sponsor's Protocol Code Number:LIMIT
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-23
    Trial 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 ConcernedSpain - AEMPS
    A.2EudraCT number2019-004975-37
    A.3Full title of the trial
    Low INR to Minimize bleeding with mechanical valves Trial
    INR bajo para minimizar el sangrado con válvulas mecánicas.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Low INR to Minimize bleeding with mechanical valves Trial
    INR bajo para minimizar el sangrado con válvulas mecánicas.
    A.3.2Name or abbreviated title of the trial where available
    LIMIT
    LIMIT
    A.4.1Sponsor's protocol code numberLIMIT
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03636295
    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 SponsorHamilton Health Sciences through the Population Health Research Institute
    B.1.3.4CountryCanada
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportHamilton Health Sciences through the Population Health Research Institute
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPHRI
    B.5.2Functional name of contact pointLIMIT Project Office
    B.5.3 Address:
    B.5.3.1Street AddressDavid Braley Cardiac Vascular Stroke Research Institute, 237 Barton Street East
    B.5.3.2Town/ cityHamilton
    B.5.3.3Post codeL8L 2X2
    B.5.3.4CountryCanada
    B.5.4Telephone number1905905 297 3479
    B.5.5Fax number1905905 297 3779
    B.5.6E-maillimit@phri.ca
    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 Yes
    D.2.1.1.1Trade name Acenocumarol
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameAcenocumarol
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 No
    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 Yes
    D.2.1.1.1Trade name Warfarin
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment with a Vitamin K Antagonist due to having a mechanical heart valve.
    Tratamiento con un antagonista de la vitamina K por tener una válvula cardíaca mecánica.
    E.1.1.1Medical condition in easily understood language
    A vitamin K antagonist is a blood thinner used to prevent blood clot formation in patients with mechanical heart valves.
    Un antagonista de la vitamina K es un anticoagulante que se utiliza para prevenir la formación de coágulos sanguíneos en pacientes con válvulas cardíacas mecánicas.
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The objective in the vanguard phase of the LIMIT trial is to assess the feasibility of recruiting 400 subjects over approximately 3 years at 5 centres.

    The objectives in the full trial are to evaluate the safety and effectiveness of a common, lower INR target range in patients with bileaflet aortic mechanical valves.
    El objetivo en la fase de vanguardia del ensayo LIMIT es evaluar la viabilidad de reclutar 400 sujetos durante aproximadamente 3 años en 5 centros.

    Los objetivos del ensayo completo son evaluar la seguridad y la eficacia de un rango objetivo común de INR más bajo en pacientes con válvulas mecánicas aórticas biliares.
    E.2.2Secondary objectives of the trial
    NA
    NA
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Have had a bileaflet mechanical heart valve implant in the aortic position ≥3 months ago,
    2) Be ≥18 years of age at the time of enrolment,
    3) Provide written informed consent (either from the patient or a substitute decision-maker).
    1) Tener un implante de válvula cardíaca mecánica bileaflet en la posición aórtica de hace ≥3 meses,
    2) Tener ≥18 años de edad en el momento de la inscripción,
    3) Proporcionar un consentimiento informado por escrito (ya sea del paciente o de una persona que tome las decisiones).
    E.4Principal exclusion criteria
    1) Have a second implanted mechanical valve (any position),
    2) Lower boundary of planned INR range is less than 2.0,
    3) Pregnant or expecting to become pregnant during the study follow-up.
    1) Tener una segunda válvula mecánica implantada (en cualquier posición),
    2) El límite inferior del rango de INR planificado sea inferior a 2,0,
    3) Estar embarazada o en espera de quedarse embarazada durante el seguimiento del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome for the vanguard phase of the trial will be the ability to recruit 400 subjects over 3 years.

    The primary outcome for the full trial will be the incidence of major bleeding over follow up.
    El resultado principal de la fase de vanguardia del ensayo será la capacidad de reclutar 400 sujetos durante 3 años.

    El resultado primario del ensayo completo será la incidencia de hemorragia mayor durante el seguimiento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    For the vanguard phase, feasibility measures will be analyzed upon reaching 400 patients. The DSMB will review safety data in the vanguard phase after 150 patients have been recruited and have completed 6 months of follow-up.

    Follow up for the full trial will occur every 6 months until 120 primary outcome events have occurred. We expect this to occur after a mean of 2 to 3 years of follow-up. After reaching 120 events, a final phone follow-up will occur with all randomized patients to allow a more thorough assessment of outcomes.
    Para la fase de vanguardia se analizarán las medidas de viabilidad al llegar a 400 pacientes. El DSMB revisará los datos de seguridad en la fase de vanguardia después de que se hayan reclutado 150 pacientes y hayan completado 6 meses de seguimiento.

    El seguimiento del ensayo completo se realizará cada 6 meses hasta que se hayan producido 120 eventos de resultado primario. Esperamos que esto ocurra después de una media de 2 a 3 años de seguimiento. Después de alcanzar los 120 eventos, se realizará un seguimiento telefónico final con todos los pacientes asignados al azar para permitir una evaluación más completa de los resultados.
    E.5.2Secondary end point(s)
    The secondary outcomes of the vanguard phase are:
    1) Proportion of established prevalent (>1 year) valve patients consented/approached,
    2) Proportion of new valve (< 1 year) patients consented/approached,
    3) Proportion of patients that crossover INR target arms,
    4) Proportion of patients prescribed concomitant antiplatelet agent,
    5) The proportion of participants at low vs. high risk (as per the PROACT definition: those without 1 of the following conditions were considered in the low-risk group: chronic atrial fibrillation, left ventricular ejection fraction <30%, left atrial dimension >50 mm, spontaneous echocardiographic contrast in the left atrium, significant vascular disease, history of neurological events within 1 year, hypercoagulability, left or right ventricular aneurysm, and women receiving estrogen replacement therapy),
    6) The estimated time in the therapeutic range in each group


    The secondary outcomes of the full trial are:
    1) All-cause mortality (selected rather than cardiovascular mortality, as cause-specific mortality is often difficult to ascertain or define in complex cardiovascular patients in whom multi-end-organ dysfunction may accompany cardiovascular decline),
    2) All bleeding,
    3) All stroke,
    4) Ischemic stroke,
    5) Hemorrhagic stroke,
    6) Type 1, 2 or 3 myocardial infarction,
    7) Systemic thromboembolism,
    8) Valve thrombosis,
    9) Pulmonary embolism,
    10) Deep vein thrombosis,
    11) New renal replacement therapy,
    12) Time in therapeutic range,
    13) Proportion of patients with extreme INR values (>4)
    Los resultados secundarios de la fase de vanguardia son:
    1) Proporción de pacientes valvulares prevalentes establecidos (> 1 año) consentidos / abordados,
    2) Proporción de pacientes con válvula nueva (<1 año) que dieron su consentimiento / se acercaron,
    3) Proporción de pacientes que superan el objetivo de INR,
    4) Proporción de pacientes a los que se prescribe un agente antiplaquetario concomitante,
    5) La proporción de participantes con riesgo bajo versus alto (según la definición de PROACT: aquellos sin 1 de las siguientes condiciones se consideraron en el grupo de bajo riesgo: fibrilación auricular crónica, fracción de eyección del ventrículo izquierdo <30%, dimensión auricular izquierda > 50 mm, contraste ecocardiográfico espontáneo en la aurícula izquierda, enfermedad vascular significativa, antecedentes de eventos neurológicos en 1 año, hipercoagulabilidad, aneurisma del ventrículo izquierdo o derecho y mujeres que reciben terapia de reemplazo de estrógenos),
    6) El tiempo estimado en el rango terapéutico en cada grupo.


    Los resultados secundarios del ensayo completo son:
    1) Mortalidad por todas las causas (seleccionada en lugar de la mortalidad cardiovascular, ya que la mortalidad por causas específicas a menudo es difícil de determinar o definir en pacientes cardiovasculares complejos en los que la disfunción multiorgánica puede acompañar al deterioro cardiovascular),
    2) Todo tipo sangrado,
    3) Todo accidentes vasculares;
    4) Accidente cerebrovascular isquémico,
    5) Accidente cerebrovascular hemorrágico,
    6) Infarto de miocardio tipo 1, 2 o 3,
    7) Tromboembolismo sistémico,
    8) Trombosis valvular,
    9) Embolia pulmonar,
    10) Trombosis venosa profunda,
    11) Nueva terapia de transplante renal,
    12) Tiempo en rango terapéutico,
    13) Proporción de pacientes con valores extremos de INR (> 4)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Follow up for the full trial will occur every 6 months until 120 primary outcome events have occurred. We expect this to occur after a mean of 2 to 3 years of follow-up. After reaching 120 events, a final phone follow-up will occur with all randomized patients to allow a more thorough assessment of outcomes.
    El seguimiento del ensayo completo se realizará cada 6 meses hasta que se hayan producido 120 eventos de resultado primario. Esperamos que esto ocurra después de una media de 2 a 3 años de seguimiento. Después de alcanzar los 120 eventos, se realizará un seguimiento telefónico final con todos los pacientes asignados al azar para permitir una evaluación más completa de los resultados.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    The vanguard phase of this trial assesses feasibility of the full trial.
    La fase de vanguardia de este ensayo evalúa la viabilidad del ensayo completo.
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    punto final ciego
    blinded end-point
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    El ensayo comparará las diferencias en un rango de INR objetivo para los pacientes que reciben terap
    Trial will compare differences in a target INR range for patients receiving ongoing VKA therapy.
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Russian Federation
    Belgium
    Germany
    Italy
    Netherlands
    Spain
    E.8.7Trial 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
    The end of the trial will be once 120 primary outcome events have occurred. We expect this to occur after a mean of 2 to 3 years of follow-up. After reaching 120 events, a final phone follow-up will occur with all randomized patients to allow a more thorough assessment of outcomes. At any point during the trial, the DSMB may recommend to stop the trial for safety reasons.
    El final del ensayo será una vez que hayan ocurrido 120 eventos de resultado primario. Esperamos que esto ocurra después de una media de 2 a 3 años de seguimiento. Después de alcanzar los 120 eventos, se realizará un seguimiento telefónico final con todos los pacientes asignados al azar para permitir una evaluación más completa de los resultados. En cualquier momento durante la prueba, el DSMB puede recomendar detener la prueba por razones de seguridad.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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.1.2.1Number of subjects for this age range: 1820
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 840
    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 No
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1000
    F.4.2.2In the whole clinical trial 2660
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    As per standard care.
    Según el cuidado estándar.
    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 Decision2021-09-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-21
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 04 16:52:19 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA