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    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7293   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:2008-005992-81
    Sponsor's Protocol Code Number:CL-N-CSM-III/01/08
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-08-04
    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 ConcernedGermany - BfArM
    A.2EudraCT number2008-005992-81
    A.3Full title of the trial
    A Prospective Randomized Double Blind Multicenter Phase III Study Comparing two Methods of Cardioplegia in Coronary Artery Bypass Surgery Custodiol-N versus Custodiol
    A.4.1Sponsor's protocol code numberCL-N-CSM-III/01/08
    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 SponsorDr. F. Köhler Chemie GmbH
    B.1.3.4CountryGermany
    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 No
    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 nameCustodiol-N®
    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 IMPIntraarterial use
    Intracardiac use
    Intracoronary use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSodium chloride
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPotassium chloride
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMagnesium chloride hexahydrate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCalcium chloride dihydrate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0,02
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHistidine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number124,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN-Acetylhistidine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number57,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSucrose
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number33,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNalpha-Ketoglutarate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1,81
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAsparaginsäure
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGlycine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAlanine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTryptophan
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDeferoxamine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0,0153
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLK614 (3,4-Dimethoxy-N-methylbenzohydroxamic acid)
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0,0062
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNArginine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3,0
    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 No
    D.3.11.8Extractive medicinal product No
    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 Yes
    D.2.1.1.1Trade name Custodiol®
    D.2.1.1.2Name of the Marketing Authorisation holderDr. F. Köhler Chemie GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCustodiol®
    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 IMPIntraarterial use
    Intracardiac use
    Intracoronary use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSodium chlorid
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPotassium chloride
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number9,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMagnesium chloride hexahydrate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHistidinhydrochloride Monohydrate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol millimole(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number18,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHistidine
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number180,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTryptophan
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMannitole
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30,0
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCalcium chloride dihydrate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0,015
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNalpha-Ketoglutarate
    D.3.10 Strength
    D.3.10.1Concentration unit mmol/l millimole(s)/litre
    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 No
    D.3.11.8Extractive medicinal product No
    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
    The study population will be selected from both genders with coronary artery disease (CAD) who are to undergo cardiopulmonary bypass for coronary artery bypass surgery. The ratio of incidence for bypass surgery in the population is 4:1 (men:women) and reflects the normal allocation/distribution of cases of the disease in the population.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level PT
    E.1.2Classification code 10011078
    E.1.2Term Coronary artery disease
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    to compare the cardioprotective effects and safety of two cardioplegic solutions, HTK Cardioplegic Solution (Custodiol) and Custodiol-N, in patients undergoing cardiopulmonary bypass for coronary artery bypass surgery
    E.2.2Secondary objectives of the trial
    to demonstrate non-inferiority in surgical outcome between Custodiol and Custodiol-N as determined by CK-MB area under the curve (primary endpoint), catecholamine requirement (cumulative dose) and cardiac Troponin T, occurrence of comorbid events postoperatively (e.g., myocardial infarction).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    (1) Patients >/=35 and </= 80 years of age
    (2) Male or female with 2 or 3 vessel coronary disease, who are scheduled for elective CBP surgery for coronary revascularisation
    (3) Presence of definite CAD for which surgical intervention is deemed necessary, without evidence of ongoing infarction. Patients with unstable angina can be included as long as there is no objective (negative cardiac isoenzymes in the immediate six hours preceding CABG, current intravenous use of nitrate therapy) or subjective (absence of prolonged symptoms suggestive of coronary insufficiency that do not respond to pharmacologic intervention) evidence of myocardial necrosis.
    (4) Eligibility for Swan-Ganz-Catheter
    (5) Able to understand character and individual consequences of the clinical trial and to provide written informed consent to participate in the study
    (6) No evidence of severe organic or psychiatric disease by history or physical examination
    (7) No history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or no any history of drug abuse or addiction within 12 months of study enrollment
    E.4Principal exclusion criteria
    (1) Patients undergoing valve repair or replacement
    (2) History of recent (< 6 weeks) Q-wave myocardial infarction
    (3) Left ventricular ejection fraction < 35% (as assessed by any one of the following: contrast ventriculography, multigated acquisition scanning [MUGA], or 2-D ECHO)
    (4) Patients on intra-aortic balloon devices or with history of previous coronary
    artery bypass surgery
    (5) Pregnant or lactating patients
    (6) Patients who have participated in any other investigational studies within 30 days previous to enrollment
    (7) Patients in cardiogenic shock (defined as a systolic BP < 90 mmHg for over one hour despite inotropic and chronotropic support)
    (8) Patients with severe chronic obstructive lung disease (FEV1 < 50%)
    (9) Previous cardiac valvular disease (clinical relevant)
    (10) Dialysis or creatinine > 2 mmol/L
    (11) BMS-Stent < 4 weeks
    (12) DES-Stent < 6 month
    (13) Guidance depended Plavix therapy
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoint:

    • CK-MB area under the curve within 24 hours (measurements 4,8,12,16,20,24 hours ± 30 min) after release of the aortic cross clamp
    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 Yes
    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) 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 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) 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.8.4.1Number of sites anticipated in Member State concerned4
    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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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 duration of the trial for each subject is expected to be 6 to 7 weeks, including 30 days Follow-up to collect data about mortality.

    The trial can be prematurely closed or suspended by the LKP or the sponsor in case of new risks for subjects become known.
    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
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state516
    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)
    In case of premature study end, all efforts will be made to follow up the subject and, all examinations scheduled for the final trial day will be performed as far as possible on all subjects and documented; all AEs/ SAEs of these subjects have to be followed up until no more signs and symptoms are verifiable or the subject is on stable condition.
    Patients who needed further treatment after study end will be treated according to current standard care.
    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 Decision2010-12-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-03-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-03-23
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