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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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).

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    Summary
    EudraCT Number:2016-001124-66
    Sponsor's Protocol Code Number:15774603
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-03-21
    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 ConcernedFrance - ANSM
    A.2EudraCT number2016-001124-66
    A.3Full title of the trial
    Evaluation of the effect of double inhibition of angiotensin II AT1 receptor and neprilysin activity on sympatic nervous system activity in patient with heart failure (B2AN-SNS)
    Etude de l’effet du blocage combiné des récepteurs AT1 de l’angiotensine II et de l’activité de la néprilysine sur l’activité du système nerveux sympathique chez l’insuffisant cardiaque (B2AN-SNS)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of the Entresto effect on sympatic nervous system in patient with heart failure (B2AN-SNS)
    Etude de l'effet de l'Entresto sur le système nerveux sympathique chez l'insuffisant cardiaque (B2AN-SNS)
    A.4.1Sponsor's protocol code number15774603
    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 SponsorUniversity Hospital Toulouse
    B.1.3.4CountryFrance
    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 supportACCO Association
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospital Toulouse
    B.5.2Functional name of contact pointCaroline Peyrot
    B.5.3 Address:
    B.5.3.1Street AddressDRCI, Hôtel-dieu Saint-Jacques, 2 rue de la Viguerie
    B.5.3.2Town/ cityToulouse
    B.5.3.3Post code31052
    B.5.3.4CountryFrance
    B.5.4Telephone number+330561778486
    B.5.5Fax number+33061778411
    B.5.6E-mailpeyrot.c@chu-toulouse.fr
    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 Entresto
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis PHARMA S.A.S
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 nameEntresto
    D.3.4Pharmaceutical form Coated 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 Yes
    D.3.11.13.1Other medicinal product typeCombination of two chemical chemical medicinal product : valsartan and Sacubitril
    D.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Not available : ATC group C09
    D.2.1.1.2Name of the Marketing Authorisation holderMultiple Holders
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical form Coated 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
    Heart failure
    Insuffisance cardiaque
    E.1.1.1Medical condition in easily understood language
    Heart failure
    Insuffisance cardiaque
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10019279
    E.1.2Term Heart failure
    E.1.2System Organ Class 100000004849
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This biomedical study will compare the effect of Entresto® and angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor on sympathic nervous system activity.
    L'objectif de cette étude biomédicale est de comparer l'effet sur l'activité du système nerveux sympathique de l'Entresto à un inhibiteur de l'enzyme de conversion ou un antagoniste du recepteur AT1 à l'angiotensine 2.
    E.2.2Secondary objectives of the trial
    - Evaluation of disease severity (NYHA stage) in the two groups at the inclusion and after the treatment period.

    - Evaluation of impact of treatment and comparator on NTpro-BNP blood serum levels after the treatment in comparaison with inclusion.
    - Evaluer la sévérité de la maladie (stade NYHA) dans les deux groupes à l’inclusion et à l’issue de la période de traitement

    - Evaluer l’impact du traitement et du comparateur sur le taux de NTpro-BNP à l’issue du traitement par rapport à l’inclusion
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Men or women of 18 years old or older with heart failure with symptomatic left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 40 %) with :
    - Functional class NYHA II and at least 2 hospitalizations for cardiac decompensation in the year with NT-proBNP ≥300 pg/ml (or BNP ≥100 pg/ml) or usage of intravenous diuretics,
    - Functional class NYHA III-IV,
    -Insufficiently controlled by alternative drug-free therapies (surgery, cardiac resynchronization ...) or well managed drug therapies: angiotensin-converting-enzyme inhibitor, AT1 receptor of angiotensin II inhibitor diuretics or beta blockers.

    • Patient member of his home social security scheme
    - Patient adulte (âge supérieur à 18 ans) présentant une insuffisance cardiaque avec dysfonction systolique ventriculaire gauche (fraction d'éjection ventriculaire gauche ≤ 40 %) symptomatique :
    • de classe fonctionnelle NYHA II ayant présenté au moins 2 hospitalisations pour décompensation cardiaque dans l’année documentée par une NT-proBNP ≥300 pg/ml (ou BNP ≥100 pg/ml) ou l’utilisation de diurétiques IV,
    • ou de classe fonctionnelle NYHA III-IV
    • insuffisamment contrôlé par les thérapeutiques non médicamenteuses (chirurgie, resynchronisation cardiaque, ...) ou médicamenteuses bien conduites : inhibiteurs de l’enzyme de conversion ou antagonistes du récepteur de l’angiotensine II, diurétiques ou bêtabloquants.

    - Patient affilié à un régime de sécurité sociale
    E.4Principal exclusion criteria
    • Patient who are receiving direct renin inhibitor like aliskiren
    • Patient who are receiving a statin
    • Patient who are receiving phosphodiestérase V inhibitors
    • Patient who are receiving a potassium-sparing drug
    • Patient with medical history of angioedema with previous treatment by angiotensin-converting-enzyme inhibitor or AT1 receptor of angiotensin II inhibitor
    • Hypersensitivity to any component of Entresto®
    • Adult protected by the law
    • Severe renal impairment (DFGe <30 ml/min/1,73 m2)
    • Severe hepatic impairment, cirrhosis or cholestasis (Child-Pugh C class)
    • Patient with are receiving anticoagulant therapies or suffering from known hemostatic trouble
    • Patient participating in another biomedical research or with an active exclusion period
    • Pregnancy
    • Breast-feeding
    o Patient recevant un inhibiteur direct de la rénine tel que l’aliskiren
    o Patient traité par une statine
    o Patient traité par un inhibiteur de la phosphodiéstérase V
    o Patient traité par un médicament hyperkaliémiant
    o Antécédent d’angioedème lié à un traitement antérieur par IEC ou ARA II
    o Hypersensibilité à un des principes actifs de l’Entresto® ou à un de ses excipients
    o patient placé sous sauvegarde de justice, tutelle ou curatelle
    o Insuffisance rénale sévère (DFGe <30 ml/min/1,73 m2)
    o Insuffisance hépatique sévère, d’une cirrhose biliaire ou d’une cholestase (classe C de Child-Pugh)
    o Patient recevant un traitement anticoagulant oral ou non ou souffrant d’un trouble connu de l’hémostase
    o Participation à une autre recherche biomédicale ou une recherche biomédicale comprenant une période d’exclusion toujours en cours à la pré-inclusion
    o Grossesse
    o Allaitement
    E.5 End points
    E.5.1Primary end point(s)
    Sympathic neural activity as assessed by microneurography by inserting an electrode directly in contact with orthosympathic efferent fibers around fibular nerve
    Valeur de l’activité sympathique à destinée musculaire mesurée par microneurographie (MSNA) au moyen d’une électrode insérée au contact des fibres orthosympathiques efférentes qui cheminent autour du nerf fibulaire.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of the study for each patient : between 3 and 12 weeks
    A la fin de l'étude pour chaque patient : Entre 3 et 12 semaines
    E.5.2Secondary end point(s)
    disease severity as assessed by NYHA stage and NT-proBNP serum levels
    Severité de la maladie mis en évidence par le stade NYHA et les taux de NT-proBNP sériques
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the end of the study for each patient : between 3 and 12 weeks
    A la fin de l'étude pour chaque patient : Entre 3 et 12 semaines
    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 No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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 Yes
    E.8.1.4Double blind No
    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 No
    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 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 No
    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
    Last visit of the last subject
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    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: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 25
    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 state50
    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)
    After their participation in the trial, patient can receive Entresto if they want to, this procedure is not include in the protocole and it will be part of the normal treatment plan of patient.
    Après leur participation à l'étude, les patients pourront recevoir l'entresto s'ils le souhaitent, cette procédure ne fais pas partie du protocole et sera comprise dans la prise en charge normale des patients
    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 Decision2016-04-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-01-11
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    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
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