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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   44339   clinical trials with a EudraCT protocol, of which   7369   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:2009-017825-21
    Sponsor's Protocol Code Number:EC09/081
    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:2010-04-16
    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 number2009-017825-21
    A.3Full title of the trial
    Prospective, randomised, double-blind study to evaluate the efficacy of treatment with melatonin in adult patients with severe sepsis or septic shock.
    Estudio prospectivo, aleatorizado, doble-ciego, para evaluar la eficacia del tratamiento con melatonina en pacientes adultos con sepsis grave o shock séptico.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Prospective, randomised, double-blind study to evaluate the efficacy of treatment with melatonin in adult patients with severe sepsis or septic shock.
    Estudio prospectivo, aleatorizado, doble-ciego, para evaluar la eficacia del tratamiento con melatonina en pacientes adultos con sepsis grave o shock séptico.
    A.4.1Sponsor's protocol code numberEC09/081
    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 SponsorINSTITUTO ARAGONÉS DE CIENCIAS DE LA SALUD
    B.1.3.4CountrySpain
    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 supportMinisterio de Sanidad y Política Social
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINSTITUTO ARAGONÉS DE CIENCIAS DE LA SALUD
    B.5.2Functional name of contact pointINSTITUTO ARAGONÉS DE CIENCIAS DE L
    B.5.3 Address:
    B.5.3.1Street AddressAVDA. GÓMEZ LAGUNA 25 3ª
    B.5.3.2Town/ cityZARAGOZA
    B.5.3.3Post code50009
    B.5.3.4CountrySpain
    B.5.4Telephone number+34976 716582
    B.5.5Fax number+34976 715554
    B.5.6E-mailemlopezh.iacs@aragon.es
    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 nameMelatonina
    D.3.2Product code Melatonina
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMELATONINA
    D.3.9.3Other descriptive nameMELATONINA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 placeboOral solution
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Severe sepsis or septic shock.
    Sepsis grave o shock séptico
    E.1.1.1Medical condition in easily understood language
    Severe sepsis or septic shock.
    Sepsis grave o shock séptico
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level PT
    E.1.2Classification code 10040070
    E.1.2Term Septic shock
    E.1.2System Organ Class 10021881 - Infections and infestations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the therapeutic efficacy of Melatonin in adult patients with severe sepsis and septic shock.
    Establecer la eficacia terapéutica de la melatonina en la evolución de los pacientes adultos con sepsis grave y shock séptico.
    E.2.2Secondary objectives of the trial
    a)To assess severe sepsis and septic shock under the influence of Melatonin treatment:
    b)Analytical parameters related to sepsis.
    c)Behavior from the circulating levels of pro- and anti-inflammatory cytokines.
    d)Oxidative and Nitrosative Stress.
    e)Acute phase response as a marker of the intensity of the systemic inflammatory response. Mainly interested in assessing the dynamic response of ITIH4 protein (Inter-Alpha-Trypsin Inhibitor Heavy Chain 4), a positive acute phase protein IL-6 dependent, as a pioneer study, in severe sepsis treated with Melatonin.
    f)Celular and humoral immune response.
    g)Endocrine response.
    a)Evaluar en la sepsis grave y shock séptico bajo la influencia del tratamiento con melatonina:
    b)Los parámetros analíticos relativos a la sepsis .
    c)El comportamiento de los niveles circulantes de citoquinas pro y antiinflamatorias.
    d)El estrés oxidativo y nitrosativo.
    e)La respuesta de fase aguda como marcador de la intensidad de la respuesta inflamatoria sistémica. Interesa sobre todo evaluar la respuesta dinámica de la proteína ITIH4 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 4), proteína de fase aguda positiva dependiente de la IL-6, como estudio pionero, en la sepsis grave y en la sepsis grave en tratamiento con melatonina.
    f)La respuesta inmune celular y humoral.
    g)La respuesta endocrina.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a) Patient admitted to the Intensive Care Unit (ICU),
    b) Aged 18 years or over.
    c) Fulfils the diagnostic criteria of severe sepsis or septic shock secondary to extrahospital or intrahospital pneumonia and/or intraabdominal infection.
    d) More than 24 hours has passed after recording the first organ dysfunction.
    e) To be receiving the standard treatments for these conditions according to universally accepted guidelines* (Dellinger RP et al, 2008) and with the antibiotherapy protocol of our ICU.
    f) Signed informed consent.
    a) Paciente ingresado en la Unidad de Cuidados Intensivos (UCI),
    b) Edad igual o superior a 18 años
    c) Cumplimiento de los criterios diagnósticos de sepsis grave o shock séptico secundarios a neumonía extrahospitalaria o intrahopitalaria y/o infección intraabdominal.
    d) Que hayan transcurrido menos de 24 horas de la documentación de la primera disfunción de órganos.
    e) Recibir el tratamiento intensivo estándar de estos padecimientos de acuerdo con las directrices universalmente aceptadas y con los protocolos de antibioterapia de nuestra UCI.
    f) Consentimiento informado firmado.
    E.4Principal exclusion criteria
    a) Absence of informed consent.
    b) Patient identified as being very close to death.
    c) Patient expected to die within 28 days from a medical condition that cannot be cured, such as a poorly controlled neoplasm or other terminal illness.
    d) History of organ transplant.
    e) Absence of concomitant intensive treatment.
    a) Ausencia de consentimiento informado.
    b) Estado moribundo en el que se percibe que la muerte es inminente.
    c) Paciente que no se espera que sobreviva 28 días debido a una condición médica que no se puede corregir, tal como una neoplasia mal controlada u otra enfermedad en fase terminal.
    d) Historia de trasplante de un órgano.
    e) Ausencia de tratamiento intensivo concomitante.
    E.5 End points
    E.5.1Primary end point(s)
    -Mortality (any cause) within 28 days of inclusion in the study. The primary cause of death will be defined: multi-organic failure induced by sepsis, respiratory failure, refractory septic shock and other causes.
    -Clinical parameters: number of days with assisted mechanical ventilation, number of days with vasoactive drugs, need of hemodyalisis or hemofiltration and number of days, other organs infection that are not the initial cause of the septic symptoms and development of failure of other organs after starting treatment.
    -Mortalidad de cualquier causa a los 28 días de inclusión en el estudio. Se determinará la causa primaria de muerte: fracaso multiorgánico inducido por la sepsis, fracaso respiratorio, shock séptico refractario y otras causas.
    -Parámetros clínicos evolutivos: días de ventilación mecánica asistida, días con drogas vasoactivas, necesidad de hemodiálisis o hemofiltración y días de la misma, sobreinfección de otros órganos distintos al causante inicial del cuadro séptico y evolución hacia el fallo de otros órganos después de iniciar el tratamiento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    - Mortality: 28 days after patient inclusion in the study.
    - Clinical parameters of patient evolution: continously within the 28 days of patient follow-up.
    - Mortalidad: a los 28 días de la inclusión de los pacientes en el estudio.
    - Parámetros evolutivos clínicos: de forma continuada durante los 28 días de seguimiento de los pacientes.
    E.5.2Secondary end point(s)
    Evaluated by the response rate of:
    -patient clinical parameters: temperature; heart and respiratory rate; blood pressure; diuresis.
    -Blood parameters related to sepsis: leucocytes; platelets; bilirubinemia; glycemia; creatinine; lactacemia; arterial gasometry; coagulation study: prothrombine activity, INR (International Normalized Ratio), partial thromboplastine time, fibrinogen, Oxidative and Nitrosative Stress markers: malonaldehyde and hydroxyl-alkenals, proteins carbonyls, antioxidant serum total activity, superoxide dismutase activity, catalase, glutathione reductase and glutathione peroxidase, nitrites concentration, erythrocytes membrane fluidity and plasmatic leveles of melatonin
    -citokines : interleukines (IL)-1β; IL-2; IL-4; IL-5; IL-6; IL-7; IL-8; IL-10; IL-12p70; IL-13 ; intereferon alpha; tumor necrosis factor (TNF)-α and granulocyte-macrophage colony stimulating factor (GM-CSF).
    -acute phase proteins: C reactive protein (CRP), haptoglobin, apolipoprotein A1 (Apo A1) and acid alpha 1-glycoprotein (α1-GPA) and Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4).
    -humoral and cellular immune response: linfocytes T, B, NK, TCD4, y TCD8 and immunoglobulins.
    -hormone profile: cortisol, aldosterone, ACTH, ADH, insuline, glucagon and 25-hydroxyvitamin D3 (25-OHD3).
    Serán la evolución de la respuesta de:
    -parámetros del estado clínico del paciente: temperatura; frecuencia cardiaca y respiratoria; tensión arterial; diuresis.
    -parámetros sanguíneos relativos a la sepsis: leucocitos; plaquetas; bilirrubinemia; glucemia; creatinina; lactacidemia; gasometría arterial; estudio de coagulación: actividad de protrombina, INR (International Normalized Ratio), tiempo de tromboplastina parcial, fibrinógeno. marcadores de estrés oxidativo y nitrosativo: malonildialdehido y 4-hidroxialquenales, restos carbonilo de las proteínas, actividad total antioxidante sérica, actividad de la superóxido dismutasa, catalasa, glutation reductasa y glutation peroxidasa, concentración de nitritos, fluidez de membrana eritrocitaria y niveles plasmáticos de melatonina.
    -citoquinas: interleucina (IL)-1β; IL-2; IL-4; IL-5; IL-6; IL-7; IL-8; IL-10; IL-12p70; IL-13; interferon (IFN)-alfa; factor de necrosis tumoral (TNF)-α y factor estimulante de colonias de granulocitos-macrófagos (GM-CSF)
    -proteínas de fase aguda: proteína C reactiva (PCR), haptoglobina, apolipoproteína A-1 (Apo A-I) y alfa1-glicoproteína ácida (α1-GPA) e Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 (ITIH4).
    -inmunidad celular y humoral: linfocitos T, B, NK, TCD4, y TCD8 e inmunoglobulinas.
    -perfil endocrino: cortisol, aldosterona, ACTH, ADH, insulina, glucagón y 25-hidroxivitamina D3 (25-OH-D3).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Dentro de los 28 días de seguimiento de los pacientes, las variables secundarias se recogen en distintos momentos temporales.
    Within the 28 days follow-up period of patients, the different secondary endpoints will be measured at different timepoints.
    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 No
    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 trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    End of study is defined as 28 days after study inclusion (considering study inclusion as the first day of melatonin or placebo administration).
    Se define el final del estudio cuando hayan transcurrido 28 días desde la inclusión en el estudio (que coincide con el primer día de administración de melatonina o placebo).
    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 months0
    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 months0
    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: 55
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 55
    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 Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state110
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 110
    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)
    Not applicable
    No aplica
    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 Decision2012-11-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-05-27
    P. End of Trial
    P.End of Trial StatusOngoing
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