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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   41200   clinical trials with a EudraCT protocol, of which   6743   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2006-006032-22
    Sponsor's Protocol Code Number:41829447 (ISRCTN No)
    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:2007-02-26
    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 number2006-006032-22
    A.3Full title of the trial
    TRial of Atorvastatin for the primary prevention of Cardiovascular Events in Rheumatoid Arthritis
    A.3.2Name or abbreviated title of the trial where available
    TRACE RA
    A.4.1Sponsor's protocol code number41829447 (ISRCTN No)
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN41829447
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity of Manchester
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    B.Sponsor: 2
    B.1.1Name of SponsorDudley Group of Hospitals NHS Trust
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameAtorvastatin
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNATORVASTATIN
    D.3.9.1CAS number 134523005
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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) Information not present in EudraCT
    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 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 Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Rheumatoid arthritis is associated with increased mortality from cardiovascular disease (CVD). Statins have a proven effect in reducing CVD events in at-risk populations, mostly due to their cholesterol-lowering properties, but possibly through anti-inflammatory and immunomodulatory effects. This trial will assess the hypothesis that atorvastatin is more effective than placebo in the primary prevention of cardiovascular events in patients with RA.
    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
    The main objective of the trial is to establish establish whether Atorvastatin used in conjunction with standard therapy for rheumatoid athritis (RA) will protect RA sufferers aged 50 years or over OR RA sufferers of 10 years or more from fatal and non−fatal cardiovascular events, myocardial infarction and stroke.

    E.2.2Secondary objectives of the trial
    1) To determine whether Atorvastatin is more effective than placebo for the control of disease activity in patients with rheumatoid athritis.

    2) To determine whether Atorvastatin is more effective than placebo in slowing radiographic joint damage
    and the long−term decline in physical function in patients with rheumatoid arthritis.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    TRACE RA Disease Activity Substudy: A nested sub-study (TRACE RA-DAS) will investigate the hypothesis that atorvastatin is more effective than placebo as adjunctive therapy in reducing RA disease activity. Patients enrolled in TRACE RA-DAS will have moderately or severely active disease at the time that they are recruited to the main study.

    Hypothesis:
    • Atorvastatin is more effective than placebo as adjuvant therapy for the control of disease activity in patients with RA
    • Atorvastatin is more effective than placebo as adjuvant therapy in slowing radiographic damage and the long-term decline in physical function in patients with RA
    • RNA samples will allow gene expression profiling studies in RA. Serum, plasma and DNA samples will also be collected for the substudy. Blood samples collected from this patient population would facilitate research in a broader array gene expression profiling approach and would allow assessment of differential expression of genes without a priori information.


    TRACE RA BioBank Substudy:

    • To develop a DNA repository for the 3808 patients with rheumatoid arthritis (RA) enrolled in the main TRACE RA study

    • To develop a plasma, serum and DNA repository for the above patients.

    • To devise and complete peer-reviewed projects on the above samples using the phenotypic and outcome data collected in the TRACE RA trial.

    • To take advantage of established population-based record-linkage capability, to allow longitudinal tracking of the subjects, thereby enabling investigation of the relationship between susceptibility genotypes and pertinent clinical features including characteristics at diagnosis, response to treatment, development of RA complications, vascular disease and survival.

    • To develop an infrastructure surrounding the collection, storage and use of these samples which concerns itself with ethics, consent, privacy and collaboration, to protect the rights of the patients whilst maintaining the highest standards of clinical research.
    E.3Principal inclusion criteria
    •Patients who satisfy 1987 ACR classification criteria for RA applied cumulatively [71]
    •Age ≥50 years old OR ≥10 years of RA disease duration
    •Written informed consent
    E.4Principal exclusion criteria
    Standard Contra−indications to statin therapy:
    1)Pregnancy, breast−feeding or women of child−bearing potential not using adequate contraception
    2)Known atherosclerotic disease i.e. previous episodes of confirmed Acute Coronary Syndrome (ACS), unstable angina; myocardial infarction with or without ST elevation; or stable CHD/CVD deemed to require statin therapy on clinical grounds, including:
    2a) Previous amputation due to severe peripheral vascular disease or severe peripheral arterial disease
    2b) Previous central or peripheral revascularisation procedure (including coronary angioplasty, coronary artery bypass graft surgery, peripheral arterial graft surgery)
    2c) Accelerated hypertension, severe heart failure (class III or IV), significant dysrhythmia or angina requiring hospitalisation in the 6 months preceding potential study entry
    2d) Uncontrolled hypertension (treated or untreated) defined as systolic blood pressure > 200 mmHg and/or diastolic blood pressure > 110 mmHg (identified as the disappearance of all sound (Korotkoff Phase V) after sitting quietly for at least 3 min)
    2e) Previous cerebrovascular accident
    2f) Other accepted indication for statin therapy according to the investigators¡ current clinical practice
    2g)Known familial hyperlipidaemia requiring drug therapy
    2h)Known diabetes
    3a)Known primary muscle disease
    3b)Known hypersensitivity or intolerance to statins
    3c)Active liver disease or hepatic dysfunction with AST or ALT >2x upper limit of normal (ULN)
    3d)Severe renal dysfunction (Creatinine >200 micromol/l)
    Creatinine phosphokinase (CK) >3xULN
    3e)Uncontrolled hypothyroidism
    3f)Taking any of the following medications:
    i)Other HMG−CoA reductase inhibitors (unless warranted as add−in therapy for post−endpoint management of study patients. In such a case during the course of the trial, it will be suggested to the managing physician to start initially Atorvastatin at a dose of 10mg daily (or equivalent dose of another statin of their choice).
    ii)Drugs known to be associated with rhabdomyolysis in combination with HMG−CoA reductase inhibitors (e.g. ciclosporin, erythromycin, azo anti−fungals, protease inhibitors and all macrolides)
    iii)Drugs (other than beta−blockers, diuretics, ACE inhibitors, other anti−hypertensive agents, oral hypoglycaemic agents and thyroxine replacement therapy) known to affect lipid levels, that interact with the study medications, or that may affect clinical laboratory parameters (such as isotretinoin).
    iv)Lipid−regulating drugs: probucol, fibrates and derivatives, bile acid sequestering resins. Patients currently taking a lipid−altering drug may be considered for screening after a 4−week wash−out period except in the case of probucol where medication must have been discontinued for at least 6 months.
    v)Drinking more than 1 240ml glass of grapefruit juice per day
    4)Participation in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study
    5)Other serious illness or significant abnormalities that may compromise the patient's safety or successful participation in the study
    6)Any illness which in the doctor's opinion means that the patient is unable to give informed consent
    7)Known alcohol abuse
    8)For the TRACE RA−DAS sub−study, intermittent systemic (intravenous or intramuscular) steroids are not allowed later than 2 month prior to measurement of clinical and laboratory outcome parameters (both at baseline or follow−up assessments for the purposes of the trial). Intra−articular steroid injections are
    allowed, but any joint injected within the previous 2 months will be counted as both tender and swollen in the
    28 joint counts.
    E.5 End points
    E.5.1Primary end point(s)
    TRACE RA: Co−primary outcomes
    i)Cardiovascular death, non−fatal myocardial infarction or stroke
    ii)As above plus coronary and carotid revascularization

    TRACE RA DAS sub−study:
    EULAR (EUropean League Against Rheumatism) moderate or good response based on Disease Activity
    Score (DAS28) at Month 6 visit

    Insufficient space to list all cardiovascular co-primary endpoint definitions.
    Please see Appendix of TRACE RA trial protocol for definitions.
    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 Yes
    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.8.3 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 concerned100
    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 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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years8
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months7
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5350
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 5350
    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 Decision2007-04-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-12-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-01-31
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