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   44300   clinical trials with a EudraCT protocol, of which   7354   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:2019-000509-58
    Sponsor's Protocol Code Number:RC31/18/0472
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2019-08-06
    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 ConcernedFrance - ANSM
    A.2EudraCT number2019-000509-58
    A.3Full title of the trial
    Cerebral hemodynamic optimization by milrinone for the prevention of delayed cerebral ischemia in severe subarachnoid hemorrhages
    Optimisation de l’hémodynamique cérébrale par la milrinone pour la prévention de l’ischémie cérébrale retardée dans les hémorragies sous-arachnoïdiennes graves
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Cerebral hemodynamic optimization by milrinone for the prevention of delayed cerebral ischemia in severe subarachnoid hemorrhages
    Optimisation de l’hémodynamique cérébrale par la milrinone pour la prévention de l’ischémie cérébrale retardée dans les hémorragies sous-arachnoïdiennes graves
    A.3.2Name or abbreviated title of the trial where available
    OPTIMIL
    OPTIMIL
    A.4.1Sponsor's protocol code numberRC31/18/0472
    A.5.4Other Identifiers
    Name:EUDRACTNumber:2019-000509-58
    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 SponsorCHU de 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 supportHealth Minister
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHU de Toulouse
    B.5.2Functional name of contact pointReglementary CRA
    B.5.3 Address:
    B.5.3.1Street AddressDRDI - Hôtel-Dieu - 2, rue Viguerie - TSA 80035
    B.5.3.2Town/ cityTOULOUSE
    B.5.3.3Post code31059
    B.5.3.4CountryFrance
    B.5.4Telephone number33561777032
    B.5.5Fax number33561778411
    B.5.6E-mailbelloc.a@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 Milrinone MEDAC 10mg/10 ml, solution injectable
    D.2.1.1.2Name of the Marketing Authorisation holderMEDAC SAS
    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 namemilrinone
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection/infusion
    D.8.4Route of administration of the placeboIntravenous drip use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    delayed cerebral ischemia in severe subarachnoid hemorrhages
    ischémie cérébrale retardée
    dans les hémorragies sous-arachnoïdiennes graves
    E.1.1.1Medical condition in easily understood language
    delayed cerebral ischemia in severe subarachnoid hemorrhages
    ischémie cérébrale retardée
    dans les hémorragies sous-arachnoïdiennes graves
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10019587
    E.1.2Term Hemorrhage subarachnoid
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluate, in comatose patients and / or sedated on D3 following a severe SAHa (WFNS IV -V), the effect of 10 days of milrinone versus placebo, in addition to the usual management, on the volume of DCI lesions measured on MRI at 1 month.
    Evaluer, chez les patients dans le coma et/ou sédaté à J3 suite à une hémorragie sous-arachnoïdienne grave par rupture d’anévrisme sécurisé, l’effet de 10 jours de traitement (à partir de J4) par milrinone versus placebo, en complément de la prise en charge
    habituelle, sur le volume des lésions d’ischémie cérébrale retardée mesurées en IRM à 1 mois
    E.2.2Secondary objectives of the trial
    Compare the two groups in terms of:
    → Radiological parameters on MRI at 1 month:
    -percentage of patients with DCI
    → Evolution in intensive care:
    •Neurological complications:
    -number and total duration of episodes of moderate and severe hypoxia
    -number of recourse to an endovascular treatment
    -intracranial hypertension in intensive care
    • Number and type of non-neurological complications
    • Variation in general and cerebral hemodynamics
    • Number of days in intensive care
    • Number of days with mechanical ventilation
    → Prognosis:
    - neurological prognosis at 1 month, 3 months, 6 months and 1 year evaluated by the modified Rankin score
    - Sickness Impact Profile (SIP-65) quality-of-life scale at 3 months, 6 months and 1 year.
    - Mortality at 1 month, 3 months, 6 months and 1 year
    - number of days of hospitalization

    → Comparison of the manual measurement method of ischemic volume on MRI at 1 month to an automated method
    → Number of adverse events

    Comparer les deux groupes en termes de:
    Paramètres radiologiques sur l’IRM cérébrale à 1 mois : pourcentage de patients ayant présenté
    une ICR
    Evolution en réanimation :
    Complications neurologiques :
    - épisodes d'hypoxie cérébrale modérée et sévère
    -nombre de recours à un geste endovasculaire cérébral
    -survenue d’une hypertension intracrânienne en réanimation
    Complications non-neurologiques
    Variation de l’hémodynamique générale et cérébrale
    Durée de séjour en réanimation Durée de ventilation mécanique
    Pronostic :
    - pronostic neurologique à 1 mois, 3 mois, 6 mois et 1 an
    - qualité de vie à 3 mois, 6 mois et 1 an
    - survie en réanimation, à 1 mois, 3 mois, 6 mois et 1 an
    -durée d’hospitalisation
    Comparer la méthode de mesure manuelle du volume
    ischémique en IRM à 1mois à une méthode automatisée
    Description de la survenue d’évènements indésirables jusqu’à la réalisation de l’IRM à 1 mois.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - patients with severe SAHa (WFNS IV and V,) whose neurological examination is impossible because of coma or need for sedation at D3
    - absence of pre-existing neurological handicap (mRS 0-2)
    - major patient
    - affiliation to social security or benefiting through a third person
    - free patient, without tutorship or curatorship or under judicial protection
    - obtaining a signed informed consent by a relative (or the person of trust) after clear and fair information about the study.
    patients présentant une HSA grave par rupture d’anévrisme intracrânien (WFNS IV et V, cf. annexe 1)
    et dont l’examen neurologique est rendu impossible par un coma ou la nécessité d’une sédation à J3
    - absence de handicap neurologique préexistant (mRS 0-2)
    - patient majeur
    - affiliation à un régime de sécurité sociale ou en bénéficiant par l’intermédiaire d’une tierce personne
    - patient libre, sans tutelle ou curatelle
    - obtention d’un consentement éclairé et signé par un proche (ou la personne de confiance) après
    information claire et loyale sur l’étude.
    E.4Principal exclusion criteria
    - patients with non-severe SAHa (WFNS I, II and III)
    - Occurrence of a documented ischemic complication during the procedure of aneurysm treatment: transient or permanent arterial occlusion, visualization of a thrombus, and dissection of an axis requiring stenting.
    - heart failure requiring inotropic administration at the time of randomization
    - ICHT at the time of randomisation (ICP> 25 mmHg for at least 20 min)
    - known severe obstructive heart diseases
    - flutter patient or atrial fibrillation
    - hypotension and / or severe hypovolemia with hemodynamic instability
    - septic shock
    - acute / chronic renal insufficiency (Cl <50ml / min)
    - major hydroelectrolytic disorders (hypokalemia <3 mmol / L)
    - known hypersensitivity to milrinone or any of the excipients
    - pregnancy, breastfeeding
    - permanent contraindications to MRI
    - patients présentant une HSA par rupture d’anévrisme non grave (WFNS I, II et III)
    - Survenue d’une complication ischémique documentée lors de la procédure de sécurisation de
    l’anévrisme: occlusion artérielle transitoire ou permanente, visualisation d’un thrombus, dissection d’un
    axe nécessitant stenting
    - défaillance cardiaque nécessitant l’administration d’inotrope au moment de la randomisation
    - HTIC au moment de la randomisation (PIC > 25 mmHg pendant au moins 20 min)
    - cardiopathies et valvulopathies sévères obstructives connues
    - patient en flutter ou ACFA
    - hypotension et/ou hypovolémie sévère avec instabilité hémodynamique
    - choc septique
    - insuffisance rénale aigue/chronique (Cl < 50ml/min)
    - troubles hydroélectrolytiques majeurs (hypokaliémie <3 mmol/L)
    - hypersensibilité connue à la milrinone ou un des excipients
    - grossesse, allaitement
    -contre-indications permanentes à la réalisation d’une IRM : pacemaker, stimulateur neurosensoriel,
    matériel ferromagnétique intraoculaire ou intracérébral, défibrillateur implantable, prothèse métallique,
    implants cochléaires.
    E.5 End points
    E.5.1Primary end point(s)
    volume of DCI lesions measured on MRI at 1 month
    volume des lésions d’ischémie cérébrale retardée mesuré sur une IRM 3T à 1 mois
    E.5.1.1Timepoint(s) of evaluation of this end point
    one month
    1 mois
    E.5.2Secondary end point(s)
    → Radiological parameters on MRI at 1 month:
    -percentage of patients with DCI
    → Evolution in intensive care:
    •Neurological complications:
    -number and total duration of episodes of moderate and severe hypoxia
    -number of recourse to an endovascular treatment
    -intracranial hypertension in intensive care
    • Number and type of non-neurological complications
    • Variation in general and cerebral hemodynamics
    • Number of days in intensive care
    • Number of days with mechanical ventilation
    → Prognosis:
    - neurological prognosis at 1 month, 3 months, 6 months and 1 year evaluated by the modified Rankin score
    - Sickness Impact Profile (SIP-65) quality-of-life scale at 3 months, 6 months and 1 year.
    - Mortality at 1 month, 3 months, 6 months and 1 year
    - number of days of hospitalization

    → Comparison of the manual measurement method of ischemic volume on MRI at 1 month to an automated method
    → Number of adverse events
    Paramètres radiologiques sur l’IRM à 1 mois :
    - pourcentage de patients ayant présenté une ICR
    Evolution en réanimation :
    Complications neurologiques :
    - nombre d'épisodes de PtiO2 au-dessous du seuil ischémique en réanimation : PtiO2 <20 mmHg (hypoxie
    modérée) et <15mmHg (hypoxie sévère) pendant au moins 15 minutes ;
    - durée totale des épisodes de PtiO2<20mmHg (hypoxie modérée) et <15mmHg (hypoxie sévère)
    - nombre de recours à un geste endovasculaire
    - survenue d’une hypertension intracrânienne en réanimation : PIC > 20 mmHg pendant au moins 15 minutes.
    Nombre et type de complications non-neurologiques
    Variation de l’hémodynamique générale et cérébrale (FC, PAM, PIC, PPC, vélocité au Doppler
    transcrânien) avec étude du débit cardiaque par échographie cardiaque transthoracique (ETT) ou étude du
    contour de l’onde de pouls avec thermodilution transpulmonaire (PICCO®)
    Nombre de jours en réanimation
    Nombre de jours avec ventilation mécanique
    Pronostic :
    - pronostic neurologique à 1 mois, 3 mois, 6 mois et 1 an (score de Rankin modifié (bon pronostic : mRS 0, 1 et 2
    / mauvais pronostic : mRS 3, 4 et 5) et le Glasgow Outcome Scale (bon pronostic : GOS 4 et 5/ mauvais pronostic
    : GOS 1, 2 et 3).
    - échelle de qualité de vie validée après accident vasculaire cérébral (Sickness Impact Profile - SIP-65) à 3 mois,
    6 mois et 1 an
    - survie en réanimation à 1 mois, à 3 mois, 6 mois et 1 an
    - nombre de jours d’hospitalisation
    Comparaison de différentes méthodes de mesure du volume ischémique en IRM à 1mois (manuelle vs.
    automatisée)
    Nombre d’évènements indésirables jusqu’à la réalisation de l’IRM à 1 mois.
    E.5.2.1Timepoint(s) of evaluation of this end point
    -1 month
    -3 month
    -6 month
    -1 year
    -1 mois
    -3mois
    -6 mois
    -1 an
    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 Yes
    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 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) No
    E.8.2.2Placebo Yes
    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 concerned5
    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 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
    LVLS
    DVDP
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    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: 234
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 234
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    comatose patients and / or sedated
    patients dans le coma ou sédaté
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state234
    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)
    none
    aucun
    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 Decision2019-10-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-10-01
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
    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 © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA