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    The EU Clinical Trials Register currently displays   35177   clinical trials with a EudraCT protocol, of which   5751   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2016-002019-16
    Sponsor's Protocol Code Number:U-2015-030
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-07-25
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2016-002019-16
    A.3Full title of the trial
    Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberU-2015-030
    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 SponsorUppsala Clinical Research center
    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 supportHjärt-lungfonden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUppsala Clinical Reseach center
    B.5.2Functional name of contact pointInger Ekman Project manager
    B.5.3 Address:
    B.5.3.1Street AddressDag Hammarskjölds väg 14B
    B.5.3.2Town/ cityUppsala
    B.5.3.3Post code75237
    B.5.4Telephone number4601861100009509
    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 Spironolaktion Pfizer Spironolakton Orion Spironolakton Takeda Spironolakton Accord Eplerenone Sandoz Eplerenone Accord Eplerenone Bluefish Eplerenone Teva Eplerenone STADA
    D. of the Marketing Authorisation holderPfizer, Orion, Takeda, Accord, Sandoz, Accord, Bleufish, Teva, STADA
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    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 nameSpironolactone, Eplerenone
    D.3.2Product code SUB10631MIG, SUB06574MIG
    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 INNspironolactone
    D.3.9.3Other descriptive nameSPIRONOLACTONE
    D.3.9.4EV Substance CodeSUB10631MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameEPLERENONE
    D.3.9.4EV Substance CodeSUB06574MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    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
    Heart Failure with Preserved Ejection Fraction, HFPEF
    E.1.1.1Medical condition in easily understood language
    Heart failure with preserved pump function
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10076396
    E.1.2Term Heart failure with preserved ejection fraction
    E.1.2System Organ Class 100000004849
    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 assess whether the initiation of spironolactone plus standard of care compared to standard of care alone reduces CV mortality and HF hospitalization in HFPEF, studied with the Registry Randomized Clinical Trial (RRCT) methodology.

    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    1. Time to CV mortality
    2. Time to first HF hospitalization and total number of HF hospitalizations Time to first hospitalization and total number of hospitalizations
    3. All-cause mortality
    4. New-onset morbidity in both groups including atrial fibrillation and diabetes mellitus
    5. Adherence to treatment assignment
    6. Effects on the primary endpoint and on CV mortality in the sub-groups EF 40-49% vs. EF ≥50%
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Written informed consent
    • Age ≥50 years
    • Stable heart failure defined by symptoms and signs of heart failure as judged by local Investigator. Patients may be enrolled as an outpatient or at or close to the time of hospital discharge
    • Most recent left ventricular ejection fraction (LVEF) ≥40% (stratified to max 2/3rd in either 40-49% or ≥50% group)
    • Most recent NT-proBNP >300 ng/L in sinus rhythm (at the time of sampling) or >750 ng/L in atrial fibrillation (at time of sampling) as an outpatient or inpatient (enrolement stratified to max 2/3rd in either sinus rhytm or atrial fibrillation group). If NT-proBNP is not available, the most recent BNP >100 pg/mL in sinus rhythm (at time of blood sampling) or >250 pg/mL in atrial fibrillation (at time of blood sampling) as an outpatient or inpatient.
    E.4Principal exclusion criteria
    •Previously enrolled in this study
    •Known EF < 40% ever
    •Current absolute indication or contraindication for MRA in judgement of Investigator. In the absence of absolute indication, patients currently treated with an MRA may have the MRA discontinued and then included in the trial, according to investigator judgement (enrollment stratified to approximately max 20% baseline MRA use in each country)
    •Known chronic liver disease
    •Probable alternative explanations for symptoms:
    -Known primary cardiomyopathy (hypertrophic with obstruction, constrictive, restrictive, infiltrative,
    -Primary hemodynamically significant valve disease
    -Right-sided HF not due to left-sided HF
    -Significant chronic pulmonary disease defined by Investigator or by requirement for home O2 or oral steroids
    -Hemoglobin < 10 g/dL (100 g/L )
    -Heart rate > 110 bpm
    •Heart transplant or LVAD recipient
    • Presence of cardiac resynchronization therapy (CRT) device
    •Systolic blood pressure <90 or >160
    •K >5.0 mmol/L
    •eGFR by MDRD < 30 ml/min/1.73m2
    Current dialysis
    •Current lithium use
    •Actual or potential for pregnancy
    •Participation in another clinical trial where a mineralcorticoid receptor antagonist is studied. Co-enrollment in trials and observational studies of other medical and device interventions is permitted
    •Not suitable in the opinion of the Investigator due to severe or terminal comorbidity with poor prognosis, or characteristics that may interfere with adherence to trial protocol
    E.5 End points
    E.5.1Primary end point(s)
    Time to CV death or first HF hospitalization
    E.5.1.1Timepoint(s) of evaluation of this end point
    After one week, 4 weeks, 6 months, 12 months treatment and at end of study. Also when needed. At the end of the study all data will be evaluated.
    E.5.2Secondary end point(s)
    • Time to CV death
    • Incidence rate for total HF hospitalizations or cardiovascular death
    • Incidence rate for total HF hospitalizations
    • Time to HF hospitalization
    • Time to all-cause mortality
    • Incidence rate for total all-cause hospitalizations
    • Time to all-cause hospitalization
    • Incidence rate for all-cause hospitalization or all-cause mortality

    • Time to sudden death or aborted cardiac arrest
    • Time to acute coronary syndrome/acute myocardial infarction
    • Time to stroke
    • Time to hospitalization for hypokalemia
    • Time to new-onset atrial fibrillation (Sweden only)
    • Time to new-onset diabetes mellitus (Sweden only)

    The following changes in potassium and renal function will be assessed by laboratory evaluations and acted upon by local investigators
    • Moderate hyperkalemia (K>5.5 mmol/L)
    • Severe hyperkalemia (K>6.0 mmol/L)
    • Moderate renal impairment: eGFR <30 mL/min/1.73 m2
    • Severe renal impairment: eGFR <20 mL/min/1.73 m2
    • Doubling of creatinine from baseline
    • Increase in K by more than 1.0 mmol/L from baseline
    • Levels of eGFR as continuous variable during follow-up
    • Levels of K as continuous variable during follow-up

    Events listed below will be collected centrally in both Sweden and the US at the end of the study
    • Time to hospitalization for hyperkalemia
    • Time to new onset hyperkalemia (outpatient encounters will be collected in Sweden only)
    • Time to dialysis
    • Time to hospitalization for renal failure
    • Time to new onset renal failure (outpatient encounters will be collected in Sweden only)

    • Time to cross-over (from spironolactone to control and from control to spironolactone)
    E.5.2.1Timepoint(s) of evaluation of this end point
    After one week, 4 weeks, 6 months, 12 months treatment and at the end of study. Also as needed. At the end of the study all data will be evaluated.
    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 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. 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E. description
    Usual care alone
    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 concerned50
    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 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
    United States
    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 years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    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: 1600
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1600
    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 state3200
    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)
    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 Decision2016-09-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-08-03
    P. End of Trial
    P.End of Trial StatusOngoing
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