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   43861   clinical trials with a EudraCT protocol, of which   7284   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

    Summary
    EudraCT Number:2016-003743-10
    Sponsor's Protocol Code Number:2016-779
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-10-14
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2016-003743-10
    A.3Full title of the trial
    Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at high cardiovascular risk: The SIMPle Randomized Clinical Trial
    Effekten af SGLT-2 hæmmere på hjertets funktion og blodforsyning hos patienter med type 2 sukkersyge og høj risiko for hjertesygdom
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Effects of SGLT-2 inhibitor on heart function and metabolism in patients with Type 2 diabetes and high risk of heart disease cardiovascular: The SIMPle Randomized Clinical Trial
    Effekten af SGLT-2 hæmmere på hjertets funktion og blodforsyning hos patienter med type 2 sukkersyge og høj risiko for hjertesygdom
    A.3.2Name or abbreviated title of the trial where available
    SIMPle
    A.4.1Sponsor's protocol code number2016-779
    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 SponsorHerlev og Gentofte Hospital
    B.1.3.4CountryDenmark
    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 supportHjerteforeningen
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportHerlev og Gentofte Hospital
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportSTENO
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportThe Toyota Foundation
    B.4.2CountryDenmark
    B.4.1Name of organisation providing supportThe Hartmann Foundation
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHerlev og Gentofte Hospital
    B.5.2Functional name of contact pointCenter for Endokrinologi
    B.5.3 Address:
    B.5.3.1Street AddressHerlev Ringvej 75
    B.5.3.2Town/ cityHerlev
    B.5.3.4CountryDenmark
    B.5.6E-mailmikkel.juergens.01@regionh.dk
    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 Jardiance
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    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.3.4Pharmaceutical form Coated 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 INNEmpagliflozin
    D.3.9.1CAS number 864070-44-0
    D.3.9.3Other descriptive nameEMPAGLIFLOZIN
    D.3.9.4EV Substance CodeSUB35915
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(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 placeboCoated tablet
    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
    Type 2 diabetes and cardiovascular risk
    E.1.1.1Medical condition in easily understood language
    Type 2 diabetes and risk of heart disease
    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
    To examine the mechanism behind the cardioprotective effects of the SGLT-2 inhibitor empagliflozine in a population of type 2 diabetics at high cardiovascular risk.
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    The effects of the SGLT-2 inhibitor empagliflozin on central hemodynamics will be studied on a subgroup of the main cohort. The dates, versions and objectives follow the main study. The endpoints of the sub-study are as follow:
    Primary endpoint
    Change in exercise PCWP at 25 watt work load (submax) from baseline to 13 weeks

    Secondary endpoints
    Change in maximal PCWP at peak exercise from baseline to 13 weeks
    Change in maximal CO at peak exercise from baseline to 13 weeks
    Change in exercise CO at 25 watt work load from baseline to 13 weeks
    Change in resting CO and PCWP in supine position and at legs up from baseline to 13 weeks
    Change in resting CVP from baseline to 13 weeks
    E.3Principal inclusion criteria
    • T2 DM (WHO criteria), diagnosed at least 3 months prior to visit 0
    • Patients with diabetes must be either untreated or treated with one or more oral anti-diabetic drugs, including incretin therapy, GLP-1 analogues or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs
    • For patients on background therapy: stable dose of anti-diabetics within 30 days prior to baseline
    • HbA1c of ≥ 48 mmol/L and ≤ 86 mmol/L at screening for patients on background therapy or HbA1c of ≥ 48 mmol/L and ≤ 75 mmol/L at screening for drug-naïve patients.
    • BMI ≤ 45 kg/m2 at screening
    • Age ≥18 years
    • Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study
    • Able to understand the written patient information and to give informed consent

    Patients must have high cardiovascular risk, defined as at least one of the following:
    • Albuminuria ( albumin/creatinine ratio ≥ 30 mg/g or plasma NT-proBNP ≥ 70 pg/ml)
    • Confirmed history of myocardial infarction (>2 months prior to baseline)
    • Heart failure according to Framingham Heart Failure Criteria
    • Patient discharged from hospital with a documented diagnosis of unstable angina within 12 months prior to baseline
    • Evidence of coronary artery disease by CAG in 1 or more major coronary arteries
    • A positive noninvasive stress test, or a positive stress echocardiography showing regional systolic wall motion abnormalities, or a positive scintigraphic test showing stress-induced ischemia,
    • History of ischemic or haemorrhagic stroke (>2 months prior to informed consent)
    • Presence of peripheral artery disease (symptomatic or not ) documented by either: previous limb angioplasty, stenting or bypass surgery; or previous limb or foot amputation due to circulatory insufficiency; or angiographic evidence of significant (> 50%) peripheral artery stenosis in at least one limb; or evidence from a non-invasive measurement of significant (>50% or as reported as hemodynamically significant) peripheral artery stenosis in at least one limb; or ankle brachial index of < 0.9
    E.4Principal exclusion criteria
    • Allergic to the study medication
    • Treatment with SGLT-2 inhibitor within 1 months prior to baseline
    • Impaired kidney function, eGFR ≤ 30 ml/min
    • Severe liver insufficiency (Child-Pugh class C)
    • ECG showing malign ventricular arrhythmia or prolonged QT-interval (>500ms)
    • Untreated clinical significant heart valve disease
    • Planned cardiac surgery or angioplasty within 3 months.
    • Myocardial infarction (MI) ≤ 30 days prior to baseline
    • Percutaneous coronary intervention (PCI) ≤ 4 weeks prior to baseline
    • History of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment
    • Prior history of heart transplantation
    • Unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure < 90 or > 180 mmHg, respectively), sick sinus syndrome or > 1st degree atrioventricular block in the absence of a functioning pacemaker
    • Requirement of emergent cardiac medical intervention or catheterization
    • Treatment with theophylline, or theophylline containing medications
    • History of known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
    • Pregnancy or desire hereof or breastfeeding.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is change in myocardial flow reserve by Rb-82 PET.
    E.5.1.1Timepoint(s) of evaluation of this end point
    From baseline to 13 weeks.
    E.5.2Secondary end point(s)
    Change in global left ventricular function assessed by echocardiography from baseline to
    13 weeks.
    Change in renal function assessed by Cr-51 EDTA from baseline to 13 weeks
    Change in plasma concentration of NT-proBNP from baseline to 13 weeks
    Change in urinary albumin/creatinine ratio from baseline to 13 weeks
    Change in HRV assessed by VAGUS from baseline to 13 weeks
    Change in daily activity, assessed by accelerometry from baseline to 13 weeks
    Change in health status by the questionnaires EQ-5D-5L and MLHFQ from baseline to 13 weeks
    Change in 24 hour BP from baseline to 13 weeks
    Change in pulse wave velocity and pulse wave analysis from baseline to 13 weeks
    Change in central and peripheral insulin resistance from baseline to 13 weeks
    Change in adipocyte differentiation, mRNA expression, macrophage infiltration and extracellular matrix fibrosis in fat tissue from baseline to 13 weeks.
    Change in biomarkers of myocardial function: NT-proBNP, MR-proANP, MR-proADM, GAL-3, hsTNT, GDF-15, PIGF and sFlt-1 from baseline to 13 weeks
    Change in biomarkers of adipocyte function: FFA, ADPN, leptin, TNF-α, IL-6, MCP-1, MAC-1, COLL-A1 and FGF-21 from baseline to 13 weeks
    Change in the blood ketone 3-beta-hydroxybutyrate from baseline to 13 weeks
    Change in the levels of AGEs CML, pentosidine and sRAGE from baseline to 13 weeks
    Change in body composition assessed by DEXA-scan from baseline to 13 weeks
    E.5.2.1Timepoint(s) of evaluation of this end point
    From baseline to 13 weeks.
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Mechanism of cardioprotective effect
    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 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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: 62
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 state92
    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)
    None
    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 Decision2016-12-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-02-06
    P. End of Trial
    P.End of Trial StatusCompleted
    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-Fri Apr 26 09:05:37 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA