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    The EU Clinical Trials Register currently displays   36818   clinical trials with a EudraCT protocol, of which   6079   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2011-004554-26
    Sponsor's Protocol Code Number:GN11GE272
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-04
    Trial results View 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 number2011-004554-26
    A.3Full title of the trial
    Multimodal effects of Thyroid hormone Replacement
    for Untreated older adults with Subclinical hypothyroidism═ż
    a randomised placebo controlled Trial (TRUST)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    -
    A.3.2Name or abbreviated title of the trial where available
    Thyroid hormone replacement for subclinical hypothyroidism
    A.4.1Sponsor's protocol code numberGN11GE272
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01660126
    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 SponsorLeiden University Medical Center, division 3
    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 supportEuropean Commission
    B.4.2CountryEuropean Union
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLeiden University Medical Center
    B.5.2Functional name of contact pointJacobijn Gussekloo
    B.5.3 Address:
    B.5.3.1Street AddressHippocratespad 21
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333 ZD
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number31715268444
    B.5.6E-mailj.gussekloo@lumc.nl
    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 Euthyrox
    D.2.1.1.2Name of the Marketing Authorisation holderMerck KGAa
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameLevothyroxine
    D.3.2Product code Not applicable
    D.3.4Pharmaceutical form Tablet
    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 INNLEVOTHYROXINE SODIUM
    D.3.9.1CAS number 55-03-8
    D.3.9.4EV Substance CodeSUB08495MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVOTHYROXINE SODIUM
    D.3.9.1CAS number 55-03-8
    D.3.9.4EV Substance CodeSUB08495MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 placeboTablet
    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
    Subclinical hypothyroidism
    Subklinische hypothyreoidie
    E.1.1.1Medical condition in easily understood language
    Thyroid hormone has multiple actions. In subclinical hypothyroidism the thyroid gland is mildly underactive. This does not cause major symptoms but may contribute to poor health in old age.
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. Does Levothyroxine treatment for SCH give multi-modal benefits for older people with SCH?

    2. Are benefits seen across a wide range of outcomes, including improving health-related quality of life, muscle function, cognition and prevention of cardiovascular disease?

    3. Are benefits seen in specific subgroups of older people with SCH, including women, very elderly and those with mild degrees of SCH (TSH 4.6-10 mU/L)?

    4. Are any benefits offset by adverse effects, such as atrial fibrillation or heart failure?
    E.2.2Secondary objectives of the trial
    i. To establish a strong European network of complementary research expertise on SCH in older people, including geriatric medicine, endocrinology and metabolic medicine, primary care, cardiovascular disease and biostatistics.
    ii. To link this research expertise with strong focus on patient perspective and needs.
    iii. To provide the necessary evidence to properly inform best practice for treatment of SCH in older people.
    iv. To disseminate this evidence to health care practitioners and patients.
    v. To improve clinical practice in management of SCH in older people.
    vi. To improve health and wellbeing of older people with SCH.
    vii. To establish a blood biobank, to be used in future research into causes and mechanisms of health, disease and disability later in life.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Community-dwelling patients aged >=65 years with SCH.

    SCH is defined as persistently elevated TSH levels (>=4.6 and ≤19.9 mU/L) and free thyroxine (fT4) in reference range measured on a minimum of two occasions at least 3 months apart.
    E.4Principal exclusion criteria
    •Subjects currently on Levothyroxine, antithyroid drugs , amiodarone or lithium.
    •Recent thyroid surgery or radio-iodine therapy (within 12 months).
    •Grade IV NYHA heart failure.
    •Prior clinical diagnosis of dementia.
    •Recent hospitalisation for major illness or elective surgery (within 4 weeks).
    •Recent acute coronary syndrome, including myocardial infarction or unstable angina (within 4 weeks).
    • Acute myocarditis or acute pancarditis
    • Untreated adrenal insufficiency
    •Terminal illness.
    •Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
    •Subjects who are participating in ongoing RCTs of therapeutic interventions (including clinical trials of investigational medicinal products [CTIMPs])
    •Plan to move out of the region in which the trial is being conducted within the next 2 years (proposed minimum follow-up period).

    Atrial fibrillation (sustained or paroxysmal) will not be an exclusion, as in itself this cardiac arrhythmia is not a contra-indication to Levothyroxine treatment. In addition, AF is a common finding in the studied age groups and exclusion of subjects with it would potentially compromise the generalisability of our results.

    Adherence to treatment allocation: drop-ins (where subjects allocated to placebo are prescribed Levothyroxine) and drop outs (where subjects allocated to Levothyroxine stop this treatment) are each estimated at less than 5% at 1 year and less than 10% at the end of the study (mean 3 years follow-up).
    E.5 End points
    E.5.1Primary end point(s)
    Change in disease specific QOL (measured using symptom and fatigue domains from the Thyroid-specific Quality of Life patient-reported outcome measure (ThyPRO) published by Watt22) – measured at baseline; 6-8 weeks; 12 months and close-out.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The ThyPRO will be measured at baseline; 6-8 weeks; 12 months and close-out.
    E.5.2Secondary end point(s)
    • General QOL (measured using EuroQOL) at baseline; 6-8 weeks; 12 months and final follow up.
    •Handgrip strength (measured using the Jamar hand dynamometer) at baseline; 12 months and final follow up.
    •Cognitive function, particularly executive function (measured using Letter Digit Coding Test [LDCT] at baseline and final follow-up.
    •Total mortality
    • Functional ability (basic Activities of Daily Living (ADL) measured using Barthel Index [BI]; extended activities of daily living measured using the older American resources and services [OARS]) at baseline and final follow-up.
    • Haemoglobin, measured on a full blood count at baseline and 12 months
    • Fatal and non-fatal cardiovascular events (this will include acute myocardial infarction; stroke; amputations for peripheral vascular disease; revascularisations for atherosclerotic vascular disease, including for acute coronary syndrome and heart failure hospitalisations).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints listed above with each secondary endpoint.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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 No
    E.8.2.4Number of treatment arms in the trial2
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA3
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Switzerland
    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
    Last visit of last subject
    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 months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months4
    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) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 750
    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 state188
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 562
    F.4.2.2In the whole clinical trial 750
    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)
    Participants who either complete or withdraw from the study treatment will be referred back to their general practitioner for their ongoing care. Any future treatment would be at the discretion of the patient’s general practitioner or treating physician in the hospital. When the research is finished and the database is locked, participants will be informed of whether they were allocated to levothyroxine or placebo and will be advised to discuss this with their GP or treating physician.
    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 Decision2012-10-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-11-20
    P. End of Trial
    P.End of Trial StatusCompleted
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