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:2006-004350-25
    Sponsor's Protocol Code Number:06-HE06-01
    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:2008-11-14
    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 ConcernedGermany - BfArM
    A.2EudraCT number2006-004350-25
    A.3Full title of the trial
    Crystalloids or colloids in patients with severe sepsis: effects on hemodynamics and tolerability of enteral nutrition
    A.3.2Name or abbreviated title of the trial where available
    CRYSTMAS protocol (CRYSTalloids Morbidity Associated with severe Sepsis)
    A.4.1Sponsor's protocol code number06-HE06-01
    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 SponsorFresenius Kabi Deutschland 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 Yes
    D.2.1.1.1Trade name Voluven 6% Infusionslösung
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi Deutschland
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPoly(O-2-hydroxyethyl)starch (130/0.4)
    D.3.9.1CAS number [9005-27-0]
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/V) percent weight/volume
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSodium chloride
    D.3.9.1CAS number [7647-14-5]
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/V) percent weight/volume
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.9
    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 Isotonische Kochsalzlösung Fresenius Infusionslösung
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi Deutschland 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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSodium chloride
    D.3.9.1CAS number [7647-14-5]
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/V) percent weight/volume
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.9
    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
    Severe sepsis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    E.1.2Level LLT
    E.1.2Classification code 10040070
    E.1.2Term Septic shock
    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 hemodynamics in patients suffering from severe sepsis who have received vascular fillings with Voluven (colloid treatment group) or NaCl 0.9% (crystalloid control group). Comparison between the two groups will be based on : * the amount of study drug (mL) required to achieve the initial hemodynamic stabilization.
    E.2.2Secondary objectives of the trial
    To explore the efficacy of Voluven® compared to NaCl 0.9% with respect to the following variables: • Time taken to achieve the initial hemodynamic stabilization. • Total quantity of study drug infused over 4 consecutive days on the ICU. • Time to start of Enteral Nutrition (subgroup of patients who received EN). • Total amount of calories received from enteral nutrition (EN) over 7 days (subgroup of patients who received EN) • Achievement of 80% of the theoretical (prescribed) calorie intake from EN (subgroup of patients who received EN). • Lengths of stay in intensive care unit and hospital. • Area under the curve (AUC) of sepsis-related organ failure assessment (SOFA) score from Screening to Day 4.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a. Prior written informed consent of the patient (if this is not possible, it will be necessary for the investigator to obtain initial informed consent according to country-specific requirements: In France an initial written informed consent by a patient’s family member [“surrogate” consent] or, if a family member is not present at the time of inclusion, to sign a declaration for inclusion in an emergency situation. Patient informed consent will be obtained as soon as the patient’s condition allows it, i.e. when patient regains consciousness). In Germany the legally authorized representative has to provide the written informed consent or in his absence a declaration for inclusion in an emergency situation is to be signed by a consultant physician who is not involved in the study and who is independent of the investigational team.
    b. Male or female patient aged 18 years or over
    c. Presence of severe sepsis defined as
    - Sepsis due to a known or suspected infection with 2 or more of the modified systemic inflammatory response syndrome (SIRS) criteria
    • Temperature (>38oC or <36oC)
    • Heart rate (>90 beats / minute)
    • Respiratory rate (>20 breaths / minute) or arterial carbon dioxide (PaCO2) <32 torr (<4.3 kPa)
    • White blood cells (WBC) >12,000 cells/mm3, <4000 cells/mm3, or >10% immature (band) forms
    - Severe sepsis for less than 24 hours with at least one of the following characteristics
    • Ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) <250
    • Arterial pH <7.3 or serum lactate level >1.5 × ULN (upper limit of normal)
    • Hypotension:
    Inadequately fluid resuscitated patients with a systolic blood pressure ≤90 mmHg or MAP ≤70 mmHg, or
    Inadequately fluid resuscitated patients requiring vasopressors to maintain blood pressure within normal ranges
    • Urine output <0.5 mL/kg/hour in patients who are inadequately fluid resuscitated
    • Platelet count <80,000/ mm3
    • Acute alteration of mental status
    d. Requirement for fluid resuscitation
    E.4Principal exclusion criteria
    a) Volume expansion with > 3 L of fluids (crystalloids and/or colloids) since diagnosis of severe sepsis b) Participation in another clinical study with an investigational drug or an investigational medical device within 30 days before Screening or during the study c) Known pregnancy; Female patients must be surgically sterile; or postmenopausal for at least two years; or if of childbearing potential must have a negative serum pregnancy test (if a test result is not available at the time of randomization, a patient may be randomized and treated initially, however, has to be withdrawn immediately from the study as soon as the test result becomes available and is positive) d) Known hypersensitivity to HydroxyEthylStarch e) Known serum creatinine > 300 µmol/L, corresponding to 3.4 mg/dL (if a serum creatinine value is not available at the time of randomization or an available value is older than 24 hours, a patient may be randomized and treated. If a creatinine value of > 300 µmol/L becomes available later, treatment with the study drug may be continued if the risk/benefit ratio for the individual patient is regarded as positive by the investigator) f) Known history of chronic renal failure (hemodialysis) g) Anuria lasting more than 8 hours (<50 mL urine output /8hours) despite fluid resuscitation prior to randomization h) Requirement for renal support (either continuous or discontinuous techniques, including intermittent hemodialysis, hemofiltration and hemodiafiltration) i) History of known hemostatic disorders with clinical bleeding (hemophilia and known or suspected Willebrand disease) j) Burns >20% of body surface k) State of brain death l) Therapeutic limitations (see appendix 11, section 2, ‘Definitions’: “…the non-introduction or non-optimisation of one or several curative or organ failure support treatments, the consequence of which may be to bring forward the time of death.”) m) Known co-morbidities: Hematologic malignant disorders, neutropenia (polymorphonuclear leukocytes < 500/mm3), proven liver cirrhosis, AIDS n) Requirement for concomitant cancer therapy (e.g. chemotherapy, radiotherapy or surgery) from randomization until Day 8 o) Fluid overload p) Subject with fluid restriction q) Refractory septic shock defined as severe sepsis with hypotension unresponsive to adequate fluid resuscitation, along with the presence of hypoperfusion abnormalities or organ dysfunction as defined by Bone et al., 1992. Patients receiving inotropic or vasopressor agents may no longer be hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunctions, yet they would still be considered to have septic schock. Patients treated with low dose vasopressors are not excluded provided they are responsive to fluid resuscitation as demonstrated by an individual fluid challenge. Patients receiving norepinephrine (noradrenaline) or epinephrine (adrenaline) at a dose > 0.5µg/kg/mn or dopamine at a dose > 15µg/kg/mn at the timepoint Screening are not eligible for the study. r) Intracranial bleeding
    E.5 End points
    E.5.1Primary end point(s)
    The primary variable is defined as the amount of study drug (mL) required to achieve the initial hemodynamic stabilization.
    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.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 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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 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
    The overall duration for the patient's participation in 90 days (+/- 7 days).
    The planned duration of enrollment is 31 months beginning July 2007 until January 2010.
    The total duration of the trial is 34 months.
    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 months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days0
    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.1.3Elderly (>=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 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 2008-11-14. Yes
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    In absence of the legally authorized representative a declaration about the emergency situation is at least to be signed by the investigator. Informed consent will be obtained when the patient regains consciousness.
    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 197
    F.4.2.2In the whole clinical trial 197
    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)
    According to 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 Decision2009-01-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-01-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-05-27
    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 08:35:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA