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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

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    Summary
    EudraCT Number:2004-004225-10
    Sponsor's Protocol Code Number:3001081
    National Competent Authority:Latvia - SAM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-01-31
    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 ConcernedLatvia - SAM
    A.2EudraCT number2004-004225-10
    A.3Full title of the trial
    Effects of peroral levosimendan in the prevention of further hospitalisations in patients with chronic heart failure. A randomised, double-blind, placebo-controlled, multi-centre, parallel-group study
    A.3.2Name or abbreviated title of the trial where available
    PERSIST
    A.4.1Sponsor's protocol code number3001081
    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 SponsorOrion Pharma
    B.1.3.4CountryFinland
    B.3.1 and B.3.2Status of the sponsorCommercial
    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 Information not present in EudraCT
    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 nameLevosimendan Capsules 0.5 mg
    D.3.4Pharmaceutical form Capsule*
    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 INNLevosimendan
    D.3.9.1CAS number 141505-33-1
    D.3.9.2Current sponsor code(-)-OR-1259
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 Information not present in EudraCT
    D.IMP: 2
    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 Information not present in EudraCT
    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 nameLevosimendan Capsules 1 mg
    D.3.4Pharmaceutical form Capsule*
    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 INNLevosimendan
    D.3.9.1CAS number 141505-33-1
    D.3.9.2Current sponsor code(-)-OR-1259
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 Information not present in EudraCT
    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 placeboCapsule*
    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
    Cardiac Failure
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 7.1
    E.1.2Level LLT
    E.1.2Classification code 10007554
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objective is to test the hypothesis that levosimendan is superior to placebo in the composite endpoint called “Patient Journey” during the 60 days following randomisation.
    E.2.2Secondary objectives of the trial
    Secondary objectives are
    • to validate the primary variable (“Patient Journey”) for phase III
    • to evaluate the efficacy of levosimendan on mortality, morbidity, symptoms and quality of life compared to placebo
    • to compare the efficacy, safety and pharmacokinetics of the two levosimendan doses
    • to compare the efficacy, safety and pharmacokinetics of levosimendan in rapid and slow acetylators
    • to evaluate the safety of levosimendan compared to placebo

    An optional pharmacogenetic substudy will be carried out under a seperate protocol. This substudy will be conducted in order to develop a better understanding of heart failure and to evaluate how patients respond to treatment with levosimendan.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1. Written Informed Consent obtained
    2. Male and female patients over 18 years of age. Women of reproductive age and potential must refrain from breastfeeding, must have a negative pregnancy test and must commit to using an acceptable method of barrier or hormonal contraception (e.g. condoms, diaphragms, oral contraceptives and long acting progestin agents) if sexually active during the study and for 1 month after the last dose of the study
    treatment. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential
    3. Chronic heart failure diagnosed at least 3 months before screening
    4. Treatment for at least 1 month before screening with angiotensin converting enzyme (ACE) inhibitor or beta-blocker and additionally at least one of the following: diuretics, digitalis, aldosterone antagonist or angiotensin II receptor blocker
    5. Left ventricular ejection fraction less than or equal to 30% as assessed by echocardiography, radionuclide ventriculography or contrast angiography within 12 months before screening
    6. NYHA IIIb-IV symptoms (dyspnoea on minimal exertion or at rest) at screening and at baseline
    7. Further evidence of severely compromised heart failure as evidenced by one of the following at screening:
    - History of at least one hospitalisation or visit to out-patient clinic for worsening heart failure requiring treatment either with intravenous (i.v.) diuretics, i.v. vasodilators, and/or i.v. inotropic agents within 6 months before screening; the index hospitalisation may be currently on-going at screening but if so, the patient must be ready to be discharged
    - Plasma N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) above or equal to 1000 pg/ml at screening
    E.4Principal exclusion criteria
    1. Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy
    2. Cardiac surgery or coronary angioplasty within 30 days before screening
    3. Acute myocardial infarction within 30 days before screening
    4. Patients who are scheduled to receive a heart transplant or left ventricular assist device or are scheduled for coronary by-pass or angioplasty in the next 6 months
    5. History of life-threatening ventricular arrhythmia within 3 months defined as an episode of resuscitated sudden death, ventricular fibrillation or sustained or haemodynamically destabilising ventricular tachycardia (wide complex tachycardia >100/min, either for >15 seconds or accompanied by hypotension,
    presyncope or syncope). Patients with one of these three arrhythmias may be enrolled if the episode was followed by placement of an intracardiac cardioverter-defibrillator (ICD) (and the ICD has not fired within 30 days)
    6. History of Torsades de Pointes or family history of long QT-syndrome
    7. Stroke or transient ischaemic attack within 3 months before screening
    8. Systolic blood pressure less than 85 mmHg at screening and baseline
    9. Heart rate 100 bpm or greater at screening and baseline
    10. Serum potassium less than 3.5 mmol/l at screening
    11. Severe renal insufficiency (serum creatinine >450 µmol/l [5.0 mg/dl]) or on dialysis
    12. Severe anaemia (blood haemoglobin <10 g/dl) at screening
    13. Significant hepatic impairment at discretion of the investigator
    14. Hypersensitivity to levosimendan
    15. Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer)
    16. Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study
    17. Administration of levosimendan within 30 days prior to screening
    E.5 End points
    E.5.1Primary end point(s)
    “Patient Journey” is a composite end-point consisting of Patient’s Global Assessment,
    worsening heart failure and mortality during the 60 days after randomisation.
    The 6-point symmetric scale of Patient’s Global Assessment, the days with worsening heart failure and days dead will be converted to numeric scale according to the Table below.
    The Global Assessment score at each visit/telephone contact represents the current day. The days between two visits/telephone contacts will be scored carrying forwards and backwards the scores to the mid-point of the two contacts. However, if the patient is experiencing worsening heart failure between two visits/telephone contacts, the Global Assessment score will be overruled and the score will be -0.5 for those days. All days after death (including the day of death) will be counted as -1.0.

    Scores of the “Patient Journey”
    Patient’s Global Assessment Score
    Very good 1.0
    Good 0.8
    Fairly good 0.6
    Fairly bad 0.4
    Bad 0.2
    Very bad 0.0
    Worsening heart failure -0.5
    Death -1.0
    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 Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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 Patient, Last Visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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 Information not present in EudraCT
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 140
    F.4.2.2In the whole clinical trial 300
    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 Decision2004-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-01-07
    P. End of Trial
    P.End of Trial StatusCompleted
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    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
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