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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   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:2021-001360-20
    Sponsor's Protocol Code Number:MINECRAFT
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-08-17
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2021-001360-20
    A.3Full title of the trial
    MINECRAFT Study: MINEralcorticoid receptor antagonism with CanRenone As eFfective Treatment in moderate to severe ARDS in COVID-19, a phase 2 clinical trial.
    Studio MINECRAFT: antagonismo del recettore dei mineralcorticordi con canrenone come trattamento efficace della ARDS da moderata a grave in COVID-19, un trial clinico di fase 2.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Impact of the intravenous administration of the diuretic canrenone together with standard therapy on clinical outcome in patients suffering for moderate-to-severe respiratory failure caused by COVID-19 infection.
    Effetto della somministrazione endovena del diuretico canrenone in aggiunta alla terapia standard sul decorso clinico di pazienti affetti da insufficienza respiratoria da moderata a grave indotta da COVID-19.
    A.3.2Name or abbreviated title of the trial where available
    Canrenone for COVID-19 patients
    Canrenone in pazienti COVID-19
    A.4.1Sponsor's protocol code numberMINECRAFT
    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 SponsorFONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
    B.1.3.4CountryItaly
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
    B.5.2Functional name of contact pointUOC CARDIOLOGIA
    B.5.3 Address:
    B.5.3.1Street AddressVia Francesco Sforza, 35
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20122
    B.5.3.4CountryItaly
    B.5.4Telephone number0255033537
    B.5.5Fax number0255033502
    B.5.6E-mailmarco.vicenzi@policlinico.mi.it
    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 LUVION - 200 MG/2 ML POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE USO ENDOVENOSO 6 FLACONI LIOFILIZZATI + 6 FIALE
    D.2.1.1.2Name of the Marketing Authorisation holderTHERABEL GIENNE PHARMA S.P.A.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameLuvion
    D.3.2Product code [Canrenoato potassico]
    D.3.4Pharmaceutical form Powder and solvent for solution for 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 INNPOTASSIO CANRENOATO
    D.3.9.1CAS number 2181-04-6
    D.3.9.2Current sponsor codePotassio canrenoato
    D.3.9.3Other descriptive namePotassium sparing diuretic
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    SARS-CoV2 infection
    Infezione da SARS-CoV2
    E.1.1.1Medical condition in easily understood language
    COVID-19
    COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level LLT
    E.1.2Classification code 10084401
    E.1.2Term COVID-19 respiratory infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The main aim of the study is to estimate the potential efficacy of i.v canrenone as add-on therapy on maximal medical treatment versus maximal medical treatment alone in treating moderate-to-severe ARDS due to SARS-CoV-2.
    Stimare la potenziale efficacia del canrenone e.v. come terapia aggiuntiva alla terapia standard versus la terapia standard da sola in pazienti affetti da sindrome da distress respiratorio acuto (ARDS) da moderata a grave in seguito ad infezione da SARS-CoV-2.
    E.2.2Secondary objectives of the trial
    1) investigate whether i.v. canrenone can modulate the COVID-19 progression;
    2) evaluate the safety profile of canrenone administration in COVID-19 patients;
    3) preliminary screening of potential new biomarkers, prognostic for clinical outcome and/or predictive of efficacy and safety of canrenone;
    4) explore the role of RAAS on SARS-CoV-2 infection.
    - Valutare se il canrenone e.v. sia in grado di modulare la progressione dell’infezione COVID-19;
    - Valutare il profilo di sicurezza della somministrazione di canrenone in pazienti COVID-19;
    - Eseguire uno screening preliminare di nuovi potenziali biomarcatori prognostici dell’outcome clinico e/o predittivi dell’efficacia e sicurezza della terapia con canrenone;
    - Esplorare il ruolo del RAAS nell’infezione da SARS-CoV-2.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age 18 – 80 y.o. Since over eighties are very fragile patients, a lot of confounding unpredictable events may interfere with the trial analyses; thus, these patients will be excluded from this exploratory proof-of-concept trial;
    - COVID-19 diagnosis through SWAB within 14 days from the beginning of symptoms
    - Hospitalization for moderate to severe ARDS (as determined by PaO2/FiO2 =300 mmHg at admission)
    - Serum concentration of potassium =4.5 mEq/L
    - Consent to participate
    - età = 18 anni e < 80 anni
    - diagnosi di COVID-19 mediante tampone entro 14 giorni dall’insorgenza dei sintomi;
    - ricovero per ARDS da moderata a grave (PaO2/FiO2 =300 mmHg al ricovero)
    - potassiemia sierica = 4.5 mEq/L
    - firma del consenso informato per la partecipazione allo studio
    E.4Principal exclusion criteria
    - Invasive mechanical ventilation
    - I.v. hydratation with Darrow’s solution or half-strenght Darrow’s solution underway
    - Acute cardiovascular event (acute myocardial infarction, acute ischaemic stroke)
    - Current malignant disease
    - Creatinine >1.8 mg/dL (for women) and >2.0 mg/dL (for men) or glomerular filtration rate <50 mL/mm
    - Systolic blood pressure <110 mmHg and/or diastolic blood pressure <60 mmHg
    - Hyponatremia
    - Anuria
    - Familial history of porphyria
    - Pregnancy or breastfeeding
    - known or suspected hypersensitivity to canrenone
    - Inclusion in any other pharmacological clinical trials
    - ventilazione meccanica invasiva;
    - idratazione e.v. con soluzione di Darrow o soluzione di Darrow dimezzata in corso
    - evento cardiovascolare acuto (infarto del miocardio, ictus ischemico)
    - patologia maligna in corso
    - creatinina >1.8 mg/dL (donne) e >2.0 mg/dL (uomini) o velocità di filtrazione glomerulare <50 mL/mm
    - pressione arteriosa sistolica <110 mmHg e/o diastolica <60 mmHg
    - iponatriemia
    - anuria
    - storia familiare di porfiria
    - gravidanza o allattamento
    - nota o sospetta ipersensibilità a canrenone
    - arruolamento in altri trial clinici farmacologici
    E.5 End points
    E.5.1Primary end point(s)
    In-hospital death. This implies that patients discharged to a long-term care facility will be classified as “discharged alive”
    Decesso durante la degenza. Questo implica che i pazienti dimessi ad un reparto per la cura a lungo termine saranno classificati come “dimessi in vita”
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary endpoint will be assessed at the event (discharge or death).
    L’endpoint primario sarà valutato all’evento (dimissione oppure decesso)
    E.5.2Secondary end point(s)
    • Need of invasive mechanical ventilation throughout hospitalization;
    • Change in SOFA score from randomization to 7 days after randomization;
    • Changes in hemodynamic and respiratory parameters (Heart Rate, Blood Pressure, PaO2/FiO2, alveolar-arterial gradient (deltaA-a), inflammatory status (CRP levels, IL-6, Ddimer and Ferritin) at 48 hours and 168 hours (7th day) from randomization;
    • Changes in features of pulmonary interstitial disease measured by chest X-Ray at 7 days after randomization in both groups;
    • Changes in [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids at randomization (T1), and after 48 hrs (T2) and 7 days (T3) and comparison between the two groups of the study;
    • Correlation between levels of [K+]hematic, renin, AngII, Ang1-7, Ang1-9, aldosterone and structurally related steroids, at basal level (randomization) and clinical outcomes (in-hospital death, need of invasive mechanical ventilation, SOFA score);
    • Duration of hospitalization for alive patients (from randomization to discharge, T4);
    • Safety endpoints:
    - Drug intolerance measured as number of AR and SAR as defined in the “Harm” paragraph;
    - Number of hypotensive events defined as systolic blood pressure constantly <90 mmHg and diastolic blood pressure constantly <60 mmHg);
    - Number of Hyperkalemia events defined as [K+]hematic >5.1 mEq/L;
    - Number of Renal failures defined as eGFR <30 ml/min.
    • Necessità di ventilazione meccanica invasiva durante l’ospedalizzazione;
    • Modifica nel punteggio SOFA dalla randomizzazione fino a 7 giorni dopo la randomizzazione;
    • Modifica nei parametri respiratori ed emodinamici, come frequenza cardiaca, pressione arteriosa, PaO2/FiO2, gradiente alveolare-arterioso, stato infiammatorio (PCR, IL-6, Ddimero e ferritina) a 48 ore e 168 ore (7 giorni) dalla randomizzazione;
    • Modifica dell’entità di interstiziopatia misurata mediante RX Torace a 7 giorni dalla randomizzazione in entrambi i gruppi;
    • Modifica nel [K+] ematico, renina, AngII, Ang1-7, Ang1-9, aldosterone (e altri steroidi con struttura correlata) alla randomizzazione (T1) e dopo 2 giorni (T2) e 7 giorni (T3) e confronto tra i due gruppi di studio;
    • Correlazione tra i livelli di [K+] ematici, AngII, Ang1-7, Ang1-9, aldosterone (e altri steroidi con struttura correlata) al basale (randomizzazione) e l’esito clinico (decesso intraospedaliero, necessità di ventilazione meccanica invasiva, punteggio SOFA);
    • Durata della degenza in ospedale per i pazienti vivi (dalla randomizzazione alla dimissione, T4);
    • Endpoints di sicurezza
    - Intolleranza al farmaco misurata come numero di reazioni avverse (sia serie che non serie)
    - Numero di eventi ipotensivi definiti come pressione sistolica costantemente <90 mmHg e diastolica costantemente <60 mmHg;
    - Numero di eventi di iperkaliemia definita come [K+] ematico >5.1 mEq/L;
    - Numero di eventi di insufficienza renale definita come eGFR <30 ml/min.
    E.5.2.1Timepoint(s) of evaluation of this end point
    48 hours/7 days after randomization and at the event (need for invasive mechanical ventilation, duration of hospitalization, safety endpoints)
    48 ore/7 giorni dalla randomizzazione e all’evento (necessità di ventilazione meccanica, durata del ricovero, endpoints di sicurezza)
    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) 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 Yes
    E.8.1.3Single blind No
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Terapia standard di cura per COVID-19
    Standard medical treatment for COVID-19
    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 Information not present in EudraCT
    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
    LVLS - Discharge or death of the last enrolled patient
    LVLS - dimissione o decesso dell'ultimo paziente arruolato
    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 months18
    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 months18
    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.1.1.1In 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: 110
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 state180
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 180
    F.4.2.2In the whole clinical trial 180
    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 discharge, patients will be followed up according to routine care, at the out-patient clinic organized at the Fondazione. This includes 3- 6- and 12-month follow-up.
    Dopo la dimissione, i pazienti saranno seguiti come da pratica clinica al centro Post-COVID-19 ambulatoriale organizzato presso la Fondazione Ca’ Granda (Milano). Questo include visite di follow-up a 3, 6 e 12 mesi.
    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 Decision2021-06-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-29
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-09-16
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