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    The EU Clinical Trials Register currently displays   37220   clinical trials with a EudraCT protocol, of which   6123   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2014-002300-24
    Sponsor's Protocol Code Number:1.0
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-01-19
    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 ConcernedUK - MHRA
    A.2EudraCT number2014-002300-24
    A.3Full title of the trial
    Albumin To prevenT Infection in chronic liveR failurE (ATTIRE)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial to investigate whether giving albumin to patients with advanced liver cirrhosis will reverse immune suppression and improve outcome from infection.
    A.3.2Name or abbreviated title of the trial where available
    Albumin To prevenT Infection in chronic liveR failurE (ATTIRE)
    A.4.1Sponsor's protocol code number1.0
    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 College London
    B.1.3.4CountryUnited Kingdom
    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 Innovations Challenge Fund (Department of Health and Wellcome Trust)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUCL Comprehensive Clincial Trials Unit
    B.5.2Functional name of contact pointZainib Shabir
    B.5.3 Address:
    B.5.3.1Street AddressGower Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC1E 6BT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number0207 679 1835
    B.5.6E-mailz.shabir@ucl.ac.uk
    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 Human Albumin 200 g/l solution for infusion (generic as per SmPC)
    D.2.1.1.2Name of the Marketing Authorisation holderHUMAN BioPlazma KFT
    D.2.1.2Country which granted the Marketing AuthorisationHungary
    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 nameHuman Albumin Solution
    D.3.4Pharmaceutical form 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 INNHuman Albumin
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Liver cirrhosis
    E.1.1.1Medical condition in easily understood language
    Infection in liver disease
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10001558
    E.1.2Term Albumin
    E.1.2System Organ Class 100000004848
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Feasibility Trial Primary objective:
    This is a trial to determine whether it is possible to restore and maintain blood albumin levels to near normal in patients admitted to hospital with complications due to advanced liver disease. The patients will be given repeated doses of 100ml 20% Human Albumin Solution (HAS) straight into their veins. HAS will be prescribed according to the albumin levels in the blood measured by standard blood tests.

    Randomised Control Trial Primary objective:
    This is a trial to confirm whether increasing the blood albumin level to near normal in patients admitted to hospital with advanced liver disease using repeated dosing of HAS will reduce chances of the development of hospital-acquired infection, organ dysfunction and death for the treatment period. Patients will be allocated at random to receive either HAS or standard medical care to compare the two treatments.
    E.2.2Secondary objectives of the trial
    Feasibility Secondary objectives:
    We shall look at how well the white blood cells (which fight infection) function in patients while they are in the study. For this study immune suppression will be considered improved by albumin if white blood cell function improves following albumin dosing.
    Clinical data will be collected on:
    1. Safety
    2. Rate of infection
    3. In-hospital mortality
    4. Total amount of fluid given
    5. Intensive Care Unit admission
    6. Organ dysfunction
    7. Duration of hospital stay
    Patients in the feasibility trial will not be followed up following discharge.

    Randomised Clinical Trial Secondary objectives:
    1. Mortality at 28 days post randomisation and at 3 & 6 months post discharge
    2. Time to outcome (first event of infection/organ dysfunction/death)
    3. Transplant within six months of treatment
    4. Total amount of albumin administered during the treatment period
    5. Duration of hospital stay
    6. Prognostic sores (predictive scores for liver disease an
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • All patients admitted to hospital with acute onset or worsening of complications of cirrhosis e.g. alcoholic hepatitis, hepatic encephalopathy, ascites, hepatic hydrothorax, hyperbilirubinaemia, oesophageal variceal bleed, any infection precipitating acute decompensation or any other presentation of acute decompensation / acute onset chronic liver failure
    • Over 18 years of age
    • Predicted hospital admission > 5 days at trial enrolment, which must be within 72 hours of admission
    • Serum albumin <30g/l at screening
    • Documented informed consent to participate (or consent given by a legal representative)
    E.4Principal exclusion criteria
    • Advanced hepatocellular carcinoma with life expectancy of less than 8 weeks
    • Patients who will receive palliative treatment only during their hospital admission
    • Patients who are pregnant
    • Severe cardiac dysfunction
    • Any clinical condition which the investigator considers would make the patient unsuitable for the trial
    • The patient has been involved in a clinical trial of Investigational Medicinal Products (IMPs) within the previous 30 days (including re-randomisation into the RCT)
    • Trial investigators unable to identify the patient (by NHS number)
    E.5 End points
    E.5.1Primary end point(s)
    Feasibility Study:
    Daily serum albumin level for the duration of the treatment period (maximum of 14 day or when the patient is considered fit for discharge if < 14 days)


    RCT:
    A composite endpoint comprising incidence of nosocomial infection, organ dysfunction and mortality within the treatment period (for a maximum of 14 days OR when the patient is considered fit for discharge if < 14 days).
    The three components of the composite endpoint are:
    1. Nosocomial Infection indicated by any new (or change in) prescribed antibiotics.
    Blinded data from a clinically representative sample of patients will be scrutinised for presence of infection by a Clinical Trial Endpoint Review Committee. The committee will contain an experienced microbiologist who will validate the presence of infection according to peer reviewed criteria.
    2. Extra Hepatic Organ Dysfunction, indicated by any new organ dysfunction within the specific organs, where measurements refer to an increase in the relevant score compared to baseline.
    3. Death (within the treatment period)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary outcomes will be collected on a daily basis for the until the end of the intervention period (up to 14 days following randomisation). The data will be evaluated at the end of the trial.
    For the feasibility stutdy the IDMC will comment on the feasibility report and advise the TSC of any concerns againt the RCT.
    No formal interim anaylysis is planned for the RCT, howevere the perioic reports will be submitted to the IDMC.
    E.5.2Secondary end point(s)
    Feasibility Study:
    Daily Leukocyte Function assessed by our laboratory based leukocyte bioassay.
    Information will also be collected on: Total volume of albumin infused; Safety; Rate of nosocomial infections; In-hospital mortality; Total amount of fluid administered; ICU admission; Organ dysfunction/prognostic score (UKELD, MELD, Child’s Pugh, CLIF-SOFA scores); Duration of hospital stay.

    RCT:
    1. Mortality at 28 days post randomisation and 3 & 6 months post discharge
    2. Time to outcome (first event of infection/organ dysfunction/death)
    3. Transplant within six months of trial treatment
    4. Total amount of HAS administered during the treatment period
    5. Duration of hospital stay
    6. Prognostic score (assessed by UKELD, MELD, CPS) at baseline and end of treatment
    7. Worst daily NEWS Score during treatment period
    8. Incidence of Systemic Inflammatory Response Syndrome (SIRS) during trial intervention period
    9. Incidence of Septic Shock during trial treatment period
    10. Days in ICU during trial treatment period
    11. Incremental cost and cost-effectiveness for up to 6 month post discharge
    12. Impact on quality of life for up to 6 month post discharge
    13. Safety and tolerability of HAS as indicated by Serious Adverse Events (SAEs)
    14. Requirement for nutritional support (nasogastric feed, nutritional supplements or total parenteral nutrition) during the trial treatment period
    E.5.2.1Timepoint(s) of evaluation of this end point
    For the secondary outcomes, this will be evaluated following intervention period in the feasilibility trial and 6 months following discharge for the RCT.
    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 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) 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard Clinical practice
    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 concerned40
    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
    Trial closure is defined as the date when all data has been received, cleaned and all queries resolved at all sites.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 757
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 189
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-01-19. Yes
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    A significant proportion of patients with liver cirrhosis will have hepatic encephalopathy when admitted or during hospital admission, this may affect their ability to give informed consent. These patients should not be excluded.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state946
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 0
    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)
    Albumin is part of current therapies in the NHS and can be given as part of standard treatment. The patient’s care team will prescribe the most suitable treatment as required and this is not expected to be any different from the patients usual treatment.
    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 CRN North Thames
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-02-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-12-11
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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