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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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:2004-001674-80
    Sponsor's Protocol Code Number:ARG-E04
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-07-04
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2004-001674-80
    A.3Full title of the trial
    A Randomised, Open, Parallel Group, Multicentre Study to Examine the Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Combination with Clopidogrel and Aspirin in Patients undergoing Elective Percutaneous Coronary Intervention (PCI), in Comparison with Unfractionated Heparin, Clopidogrel and Aspirin.
    A.3.2Name or abbreviated title of the trial where available
    Argatroban as Anticoagulant in PCI
    A.4.1Sponsor's protocol code numberARG-E04
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberN/A
    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 SponsorMitsubishi Pharma Corporation
    B.1.3.4CountryJapan
    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.2.1.1.1Trade name Novastan 100mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderMitsubishi Pharma Europe
    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 nameArgatroban
    D.3.2Product code MCI-9038
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    Intravenous bolus use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNArgatroban
    D.3.9.1CAS number 74863-84-6
    D.3.9.2Current sponsor codeMCI-9038
    D.3.9.3Other descriptive nameSynthetic direct thrombin inhibitor (DTI)
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100 mg/ml in to 2.5 ml vial=250mg
    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 No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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.2.1.1.1Trade name Monoparin® heparin sodium (mucous) 1000 units/ml 10 ml ampoules
    D.2.1.1.2Name of the Marketing Authorisation holderCP Pharmaceuticals Ltd.
    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 nameUnfractionated Heparin (UFH)
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    Intravenous bolus use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHeparin sodium (mucous)
    D.3.9.1CAS number 9041-08-1
    D.3.9.2Current sponsor code10,000 units (IU)/vial
    D.3.9.3Other descriptive nameUnfractionated Heparin (UFH)
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number10,000 units to per vial
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 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
    Stable coronary artery disease (CAD) or unstable angina (troponin negative, i.e. within the normal range for the study site) with low to moderate anatomic risk and a requirement for elective percutaneous coronary angioplasty or stent insertion with an approved device in one or more de novo-treated or re-stenotic lesions in native vessels.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 7.1
    E.1.2Level LLT
    E.1.2Classification code 10011078
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To obtain information about the safety and effects on various pharmacodynamic markers, of three doses of argatroban when used in combination with clopidogrel and aspirin.
    E.2.2Secondary objectives of the trial
    To assess the results of three doses of argatroban when used in combination with clopidogrel and aspirin and UFH when used in combination with clopidogrel and aspirin on clinical outcomes (composite and each of all-cause and cardiovascular death, myocardial infarction, urgent revascularisation at day 30, and major and minor bleeding episodes during hospital stay), adequacy of anticoagulation, various pharmacodynamic markers, pharmacokinetics and the incidence of heparin antibodies.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    To participate in this trial, patients must meet all of the following criteria:

    1. Male or female (women of child bearing potential must have a negative pregnancy test prior to entry into the study)

    2. Aged over 18 years

    3. Diagnosis of stable coronary artery disease (CAD) or unstable angina (troponin negative, i.e. within the normal range for the study site) with low to moderate anatomic risk and a requirement for elective percutaneous coronary angioplasty or stent insertion with an approved device in one or more de novo-treated or re-stenotic lesions in native vessels

    4. Signed written informed consent
    E.4Principal exclusion criteria
    Patients meeting any of the following criteria will be excluded from participation in the study:

    1. Any condition which, in the investigator’s opinion, contraindicates the use of argatroban, heparin or clopidogrel or endangers the patient if he/she participated in this study.

    2. Known cirrhosis, hepatitis, clinically significant hepatic disorder, or history of hepatic disorder. Hepatic disorder is defined as having levels of liver function tests (bilirubin, AST (SGOT), ALT (SGPT) greater than 3.0 times above the upper limit of the normal range of local laboratory.

    3. Patients not currently taking aspirin.

    4. Renal insufficiency, defined as serum creatinine greater than 2.0 mg/dL (greater than 177micromol/L).

    5. Platelets less than 125,000/microl.

    6. If already taking any form of heparin prior to study enrolment, aPTT equal or greater than 35 sec or ACT greater than 160 sec.

    7. Use of low molecular heparin (LMWH) during 12 h prior to PCI.

    8. If taking oral anticoagulant medication prior to study enrolment, INR greater than 1.2.

    9. Q wave MI with cardiogenic shock or thrombolytic therapy within 72 h of study dosing.

    10. Use of GPIIb/IIIa inhibitors within prior 3 weeks.

    11. Documented coagulation disorder or bleeding diathesis.

    12. Lumbar puncture within the past 2 weeks.

    13. History of previous cerebral aneurysm, haemorrhagic stroke, or thrombotic stroke within the past 6 months.

    14. Active, uncontrolled peptic ulcer disease or any gastrointestinal bleeding or genitourinary bleeding within 3 months prior to study enrolment.

    15. Major surgery, serious trauma, puncture of non-compressible vessel, or biopsy of parenchymal organ within prior 2 months.

    16. Planned staged procedure, planned rotational atherectomy, directional coronary atherectomy, brachytherapy, or thrombectomy catheters.

    17. Planned surgical intervention other than study procedure within next 7 days.

    18. Presence of greater than 50% stenosis of unprotected left main coronary artery.

    19. Severe peripheral vascular disease, precluding femoral access.

    20. History of vasculitis.

    21. Uncontrolled hypertension defined as greater than 180/120 mmHg.

    22. Pregnancy (exclusion by routine urine test).

    23. Lactating woman.

    24. Woman of children bearing age who are or were not using accepted contraceptive methods.

    25. Participation in other clinical trials of investigational products within 3 months prior to study enrolment.

    26. Terminally ill patients with a life expectancy of < 3 months.
    E.5 End points
    E.5.1Primary end point(s)
    A. Triple and quadruple composite and each of all-cause (and cardiovascular) death, myocardial infarction (MI), and urgent revascularisation at Day 30, and major bleeding events during hospital stay

    B. Minor Bleeding Events during Hospital Stay

    C. ACT value after the first dosing of study treatment (5 - 10 mins after completion of bolus)

    D. Effects on pharmacodynamic markers, including some or all of:
    aPTT and activated clotting time (ACT), thrombin-antithrombin complex (TAT), D-dimer, ecarin test (ECAT), endogenous thrombin potential (ETP), prothrombinase-induced clotting time (PiCT), troponin (Tn), CD40L, C-Reactive Protein (CRP), Interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-alpha), tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), low concentration ADP-induced platelet aggregation and monocyte chemotactic protein-1 (MCP-1)
    Measurements for D-Dimer, TAT, CD40L and CRP will be measured at baseline and 24 h, other measurements will be taken at baseline (prior to argatroban or UFH dosing), 5 - 10 mins and 30 mins after completion of bolus, at end of PCI procedure, 2 h after end of PCI procedure, and at 24 h after the end of the PCI procedure/hospital discharge

    E. Number of additional boluses needed to reach minimum ACT target of 250 sec (maximum of two additional for argatroban)

    F. Pharmacokinetic assay (for argatroban treatment arms): samples will be taken at baseline (prior to argatroban or UFH dosing), 5 - 10 mins and 30 mins after completion of bolus, every 30 mins until the end of PCI procedure, at the end of the procedure and every 30 mins up to 2 h after the end of the PCI procedure

    G. Anti-heparin/PF4 antibody assay: samples will be taken at baseline (prior to argatroban or UFH dosing) and at the 30 days follow-up visit (for randomised patients)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    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 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) 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 Yes
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    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) Yes
    E.8.2.2Placebo No
    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 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 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
    The planned termination for this study will be at day 30 for all 140 patients. On completion of the study, the termination page of the screening CRF will be completed.

    Premature termination of the study must be mutually agreed upon by the Lead Investigator and Mitsubishi Pharma Corporation and must be documented. However, study results will be reported according to the requirements outlined in this protocol as far as applicable.
    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 months0
    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 months0
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-07-04. Yes
    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 Yes
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 140
    F.4.2.2In the whole clinical trial 140
    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)
    Normal, health-care provider and standard treatment.
    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 Decision2005-04-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-09-13
    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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