Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43889   clinical trials with a EudraCT protocol, of which   7298   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools

    < Back to search results

    Print Download

    EudraCT Number:2019-003959-11
    Sponsor's Protocol Code Number:1703001
    National Competent Authority:Norway - NOMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-03-17
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNorway - NOMA
    A.2EudraCT number2019-003959-11
    A.3Full title of the trial
    MUscle Side-Effects of atorvastatin in coronary patients (MUSE) follow-up study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MUscle Side-Effects of cholesterol drugs in coronary heart disease patients (MUSE) follow-up study
    A.4.1Sponsor's protocol code number1703001
    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 SponsorVestre Viken Trust
    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 supportVestre Viken Trust Drammen hospital
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVestre Viken Trust
    B.5.2Functional name of contact pointjohn Munkhaugen
    B.5.3 Address:
    B.5.3.1Street AddressDronninggata 41
    B.5.3.2Town/ citydrammen
    B.5.3.3Post code3004
    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. name atorvastatin
    D. of the Marketing Authorisation holderMylan®
    D.2.1.2Country which granted the Marketing AuthorisationNorway
    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 No
    D.3.7Routes of administration for this IMPOral use
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Coronary heart disease patients With perceived statin Associated muscle symptoms or statin discontinuaton due to muscle symptoms
    E.1.1.1Medical condition in easily understood language
    Coronary heart disease patients who report muscle symptoms during treatment with atorvastatin or who have stopped taking their atorvastatin pill due to muscle symptoms
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    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 primary objective is to develop an accurate diagnostic test that can be used in clinical practice to differentiate true statin associated muscle symptoms (SAMS) and non-SAMS (i.e. muscle symptoms not related to the atorvastatin treatment) among coronary heart disease patients with self-perceived SAMS, thereby allowing efficient diagnostics and actions to prevent future cardiovascular events.
    E.2.2Secondary objectives of the trial
    The key secondary objectives are:
    - To determine the relationship between SAMS and atorvastatin lactone metabolites in skeletal muscle, and to evaluate the metabolite concentrations in muscle as a diagnostic tool for true SAMS.
    - To determine the relationship between SAMS and inhibition of the mevalonate pathway in skeletal muscle, and to evaluate the concentration of mevalonate pathway intermediates in muscle as a diagnostic tool for true SAMS.
    -To determine the relationship between SAMS and inhibition of mitochondrial function in skeletal muscle, and to evaluate the use of mitochondrial respiratory enzymes in muscle as a diagnostic tool for true SAMS.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event 6-36 months prior to study start and prescribed atorvastatin.
    -Self-reported muscle complaints (i.e. pain, weakness, tenderness, stiffness or cramp to the body of any intensity) that they attribute to atorvastatin therapy at study inclusion • Self-reported muscle complaints that has led to atorvastatin discontinuation at study inclusion
    -previous participation in the MUSE trial (eudract no 2018-004261-14)
    E.4Principal exclusion criteria
    • First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event the past 12 months prior to study start in high risk patients (i.e. at least one of following comorbid conditions: systolic heart failure, >1 previous myocardial infarction, kidney failure, diabetes, and smokers)
    • First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event the past 6 months prior to study start in low risk patients without any of the co-morbid conditions mentioned above and in patients who are not taking a statin at all
    • Patients with residual stenosis on the major coronary arteries that were not revascularized at the time of the index event, patents with symptomatic peripheral artery disease and patients with familial hypercholesterolemia
    • Patient has any contraindications for atorvastatin listed in the Summary of Product Characteristics (i.e. known hypersensitivity to the ingredients, acute liver failure/ ALT > 3 times upper limit of the normal range in blood at study start, pregnancy and breastfeeding )
    • History of previous rhabdomyolysis, myopathy or liver failure due to statin treatment with CK > 10 times upper limit of the normal range or ALT > 3 times upper limit of the normal range.
    • Any condition (e.g. psychiatric illness, dementia) or situation, that in the investigator’s opinion could put the subject at significant risk, confound the study results, interfere significantly with the subject participation in the study, or rendering informed consent unfeasible
    • Short life expectancy due to other medical conditions
    • Not being able to understand Norwegian.
    • Women of childbearing potential defined as a premenopausal female capable of becoming pregnant.
    • Participation in another randomized clinical trial
    E.5 End points
    E.5.1Primary end point(s)
    The primary end-point will be assessed by the individual mean difference in muscular symptom intensity between treatment periods with statin and placebo, reported by the patients over the last three weeks (i.e. week 4-7) measured with aggregated Visual Analogue Scale (VAS) scores
    E.5.1.1Timepoint(s) of evaluation of this end point
    At study start, during the 7x2 weeks treatment period and at study end
    E.5.2Secondary end point(s)
    Assessment of the secondary study end-points will be ascertained through the self-reported diary and blood samples collected at baseline, during the treatment periods, and at study-end :
    - Levels of atorvastatin and its metabolites in muscle tissure, blood plasma and white blood cells.
    - Levels of the following mevalonate pathway intermediates in muscle, blood plasma and PBMC: Mevalonate, farnesyl-PP and geranylgeranyl-PP (calculated as the atorvastatin-mediated reduction [i.e. relative difference between on and off statin], and as the absolute Levels
    - Levels of the following Target protein in muscle and PBMC: The HMGCR protein expression, the ratio HMGCR protein / atorvastatin total sum, the HMGCR protein / atorvastatin lactone metabolites, the HMGCR protein / atorvastatin acid metabolites (calculated as the absolute levels)
    - Levels of the following enzymes in the mitochondrial respiratory chain in muscle and PBMC: The enzyme activity and protein expression of Complex I, II, III, IV and IV (calculated as the atorvastatin-mediated reduction [i.e. relative difference between on and off statin], and as the absolute levels)
    - Levels of the following combined target protein expression and drug: the ratio Complex III protein / atorvastatin total sum, the Complex III protein / atorvastatin lactone metabolites, the Complex III protein / atorvastatin acid metabolites (calculated as the absolute levels)
    - Levels of apoptosis biomarkers in muscle: Caspase-3, Bad, Bak, Bax, Bax/Bcl-2 dimer, Bcl-xL, Bcl-xL/Bak dimer, Smac, calpain activity (calculated as the atorvastatin-mediated alteration [i.e. relative difference between on and off statin], and as the absolute levels)
    - Statin adherence measured with indirect (self-reported questionnaires and pill counts of returned packages) and direct (liquid chromatography-tandem mass spectrometry) methods.
    E.5.2.1Timepoint(s) of evaluation of this end point
    After each 7 weeks treatment period
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence Yes
    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. 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 No
    E.8.1.1Randomised No
    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 Yes
    E. trial design description
    open prospecitve non randomized intervention study
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    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 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 No
    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 years0
    E.8.9.1In the Member State concerned months6
    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 months6
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state30
    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)
    Telephone interview after 3 months performed by study PI will reveal experiences with study participation, current statin treatment, muscle complaints and occurence of SAEs
    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 Decision2020-05-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-25
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands