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    The EU Clinical Trials Register currently displays   41449   clinical trials with a EudraCT protocol, of which   6808   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-004318-25
    Sponsor's Protocol Code Number:NL63681.029.18
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-06-08
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2017-004318-25
    A.3Full title of the trial
    Early high-dose vitamin C in post-cardiac arrest syndrome.
    Vroege hoge dosis intraveneuze vitamine C na reanimatie.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Early high-dose vitamin C to prevent and/or treat organ dysfunction after cardioplumonary resusciation.
    Vroege hoge dosis intraveneuze vitamine C na reanimatie.
    A.3.2Name or abbreviated title of the trial where available
    Vitamin C post cardiac arrest
    Vitamine C na reanimatie
    A.4.1Sponsor's protocol code numberNL63681.029.18
    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 SponsorVU University Medical Center
    B.1.3.4CountryNetherlands
    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 supportThe Netherlands Organisation for Health Research and Development
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVU University Medical Center
    B.5.2Functional name of contact pointDept. of Intensive Care
    B.5.3 Address:
    B.5.3.1Street AddressDe Boelelaan 1117
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1081 HV
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31204443924
    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 nameAscorbic acid 5 gr/50 ml
    D.3.2Product code 1.5 gr and 5 gr
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAscorbic acid
    D.3.9.3Other descriptive nameASCORBIC ACID PH EUR
    D.3.9.4EV Substance CodeSUB29103
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameAscorbic acid 100 mg/ml
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAscorbic acid
    D.3.9.3Other descriptive nameASCORBIC ACID PH EUR
    D.3.9.4EV Substance CodeSUB29103
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 placeboInfusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients admitted to the Intensive Care after out-of-hospital cardiac arrest with return of spontaneous circulation, ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm and EMV-score ≤8
    Patiënten opgenomen op de Intensive Care na een reanimatie buiten het ziekenhuis met herstel van spontane circulatie, ventrikel fibrilleren of ventrikel tachycardie als eerste geregistreerde ritme en een EMV-score ≤8
    E.1.1.1Medical condition in easily understood language
    Patients admitted to the Intensive Care after after cardiopulmonary resuscitation who remain comatose
    Patiënten opgenomen op de Intensive Care na een reanimatie buiten het ziekenhuis die buiten bewustzijn blijven
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10078202
    E.1.2Term Post cardiac arrest syndrome
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To determine whether an early high dose i.v. vitamin C can improve organ function, especially neurological outcome, in patients after cardiac arrest
    - Kan een vroeg toegediende, hoge dosis i.v. vitamine C orgaan functie (in het bijzonder neurologische uitkomst), verbeteren in patienten na reanimatie?

    E.2.2Secondary objectives of the trial
    - To explore the optimal dosing regimen for high dose i.v. vitamin C
    - To investigate in vitro the difference in effect of plasma obtained from post cardiac arrest patients treated with placebo, 3 gr/day or 10 gr/day vitamin C on endothelial cell viability and underlying oxidative pathways.
    - Indien vitamine C orgaanfunctie verbetert, werkt 3 gr/dag dan beter dan 10 gr/dag?
    - Is er in vitro verschil in effect van het plasma van de studiepatiënten op endotheliale celdood en wat zijn de onderliggende oxidatieve mechanismen?
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients suffering an out-of-hospital cardiac arrest with return of spontaneous circulation, ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm and EMV-score ≤8 will be included.
    Patiënten op de Intensive Care opgenomen na een reanimatie buiten het ziekenhuis met herstel van spontane circulatie, ventrikel fibrilleren of ventrikel tachycardie als eerste geregistreerde ritme en een EMV-score ≤8 zullen worden geincludeerd.
    E.4Principal exclusion criteria
    Patients with pre-existent terminal renal insufficiency (i.e. receiving renal replacement therapy (RRT)), known glucose 6-phosphate dehydrogenase deficiency (risk of hemolysis), history of urolithiasis, oxalate nephropathy, hemochromatosis or treatment limitations will be excluded.
    Patiënten met in de voorgeschiedenis pre-existente terminale nierinsufficiëntie (d.w.z. het ontvangen van nierfunctie vervangende therapie), glucose 6-phosphate dehydrogenase deficientie (risico op hemolyse), urolithiasis, oxalate nefropathie, hemochromatose of behandel beperkingen zullen worden geexcludeerd.
    E.5 End points
    E.5.1Primary end point(s)
    We will determine organ failure at 96 hours measured by the delta (Δ) Sequential Organ Failure Assessment (SOFA) score. ΔSOFA score is defined as the difference between SOFA admission and SOFA at 96 hour. Death at 96-hours will be counted as the maximum SOFA score (24 points).
    We onderzoeken orgaanfalen na 96 uur gekwantificeerd door de delta (Δ) Sequential Organ Failure Assessment (SOFA) score. ΔSOFA score is gedefinieerd door het verschil tussen SOFA bij opname en SOFA na 96 uur. Overleden na 96 uur zal berekend worden als de maximale SOFA score (24 punten).
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 96 hours
    Na 96 uur
    E.5.2Secondary end point(s)
    As secondary outcomes we will investigate: neurological outcome (Maximal Glasgow Coma Score at 96-h and and the end of ICU-stay; Cerebral Performance Categories scale and Modified Rankin Scale at 30 and 180 days; HUI-3 questionnaire at 180 days; neuron-specific enolase day 1, 2 and 3); clinical parameters (IC- and hospital stay, 30-day and 90-day mortality), organ injury (myocardial injury measured by troponin and CK-MB (maximum day 1), lung injury score, ventilation time, renal function, need of renal replacement therapy, IC-acquired weakness (Medical Research Council score), delirium (CAM-ICU score), oxidative stress parameters (such as F2-isoprostanes and oxidation reduction potential (ORP)), anti-oxidant capacity (AOC) and vitamin C plasma concentrations.

    In vitro experiments:
    To determine the different effect of 3 or 10 gram vitamin C or placebo on the underlying oxidative pathways we will investigate how plasma obtained from the trial patients affects cultured human systemic microvascular endothelial cells with regard to endothelial cell viability, ROS production intracellular vitamin C concentrations, NADPH-oxidase expression, p47Phox expression, endothelial barrier function and mitochondrial respiratory chain function.
    Als secondaire uitkomstmaten zullen we onderzoeken: neurologische uitkomst (Maximale Glasgow Coma Score na 96 uur en aan het einde van de IC-opname; Cerebral Performance Categories scale en Modified Rankin Scale na 30 en 180 dagen, HUI-3 vragenlijst na 180 dagen; neuron-specific enolase dag 1, 2 en 3); klinische parameters (IC- en ziekenhuis ligduur, 30-dagen en 90-dagen mortaliteit), orgaan schade (myocardiale schade gemeten door troponine en CK-MB (maximum van dag 1), lung injury score, beademingsduur, nierfunctie, noodzaak tot nierfunctie-vervangende therapie, IC-acquired weakness (Medical Research Council score), delier (CAM-ICU score), oxidatieve stress parameters (zoals F2-isoprostanen en oxidatie reductie potentiaal (ORP)), anti-oxidante capaciteit (AOC) en vitamine C plasma concentraties.

    In vitro experimenten: om het verschil in effect te bepalen van 3 gr of 10 gr vitamine C per dag of placebo op de onderliggende oxidatieve mechanismen zullen we het effect onderzoeken van plasma verkregen van de trial patienten op gekweekte humane systemische microvasculaire endotheliale cellen met betrekking tot endotheliale cel overleving, ROS productie, intracellulaire vitamine C concentraties, NADPH-oxidase expressie, p47Phox expressie, endotheliale barriere functie en mitochondriale respiratoire keten functie.
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 96 hours and at the end of ICU-stay. Neurological outcome will also be evaluated after 30 days and after 180 days.
    Na 96 uur en aan het einde van de IC-opname. Neurologische uitkomst zal ook onderzocht worden na 30 en 180 dagen.
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 No
    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 Yes
    E.8.2.3.1Comparator description
    Andere dosis
    Other dosage
    E.8.2.4Number of treatment arms in the trial3
    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 concerned9
    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
    When the last subject has finished his/her follow up of 180 days.
    Als de laatste patient gedurende 180 dagen gevolgd is.
    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
    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: 130
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 230
    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
    Comatous patients admitted to the Intensive Care after cardiac arrest.
    Comateuze patiënten die opgenomen worden op de intensive Care na reanimatie.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state360
    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.
    Extra note with regard to the planned number of subjects to be included:
    Eventually, we aim to include in this RCT 270 EVALUABLE patients. To achieve the inclusion of this number of evaluable patients, we expect that we have to randomize 360 patients.
    Geen.
    Uiteindelijk willen we in deze RCT 270 EVALUEERBARE patiënten hebben. Om dit aantal te bereiken verwachten we ongeveer 360 patiënten te zullen moeten randomiseren.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Tergooiziekenhuizen
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation Ziekenhuis Gelderse Vallei
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 3
    G.4.1Name of Organisation Sint Franciscus Gasthuis & Vlietland
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 4
    G.4.1Name of Organisation Erasmus Medisch Centrum
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 5
    G.4.1Name of Organisation Noordwest Ziekenhuisgroep
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 6
    G.4.1Name of Organisation Amphia Ziekenhuis
    G.4 Investigator Network to be involved in the Trial: 7
    G.4.1Name of Organisation Maasstad Hospital
    G.4.3.4Network Country Netherlands
    G.4 Investigator Network to be involved in the Trial: 8
    G.4.1Name of Organisation OLVG Oost
    G.4.3.4Network Country Netherlands
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-06-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-16
    P. End of Trial
    P.End of Trial StatusOngoing
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