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    The EU Clinical Trials Register currently displays   43843   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:2013-001048-73
    Sponsor's Protocol Code Number:BAY41-6551/13084
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-05-20
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2013-001048-73
    A.3Full title of the trial
    A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients with Gram-Negative Pneumonia
    Prospektivní, randomizovaná, dvojitě zaslepená a placebem kontrolovaná multicentrická studie ověřující bezpečnost a účinnost přípravku BAY 41-6551 jako adjuvantní léčby u intubovaných a mechanicky ventilovaných pacientů s pneumonií způsobenou gramnegativními bakteriemi
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to test the safety and effectiveness of Bay 41-6551 as additional therapy to standard of care antimicrobial treatment in patients who have Gram-Negative Pneumonia and are intubated and mechanially ventilated
    A.4.1Sponsor's protocol code numberBAY41-6551/13084
    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 SponsorBayer AG
    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 supportBayer AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street Address-
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.6E-mailclinical-trials-contact@bayer.com
    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 nameAmikacin Sulfate 1:1.8 Solution for Inhalation
    D.3.2Product code BAY41-6551
    D.3.4Pharmaceutical form Nebuliser solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAmikacin
    D.3.9.2Current sponsor codeBAY41-6551
    D.3.9.3Other descriptive nameAmikacin sulfate 1:1.8
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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.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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboNebuliser solution
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Gram-negative pneumonia
    E.1.1.1Medical condition in easily understood language
    Pneumonia
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10035701
    E.1.2Term Pneumonia gram-negative bacterial NOS
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate that as adjunctive therapy to IV antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the PDDS Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative pneumonia.
    E.2.2Secondary objectives of the trial
    - To evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality to the LFU visit,
    - To evaluate the Early Clinical Response at Day 10,
    - To evaluate the days on ventilation through the LFU visit,
    - To evaluate the days in the ICU at the LFU visit.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males and non-pregnant, non-lactating females, 18 years of age or older. For females of child-bearing potential, one of the following medically acceptable contraceptive methods must be used: or they agree to abstain from heterosexual intercourse while participating in the study. One or more of these methods should be used during the study and continue for 30 days after completion of the antibiotic therapy.
    a) Double-barrier methods of contraception (eg, condoms plus spermicidal foam)
    b) Intrauterine contraceptive device
    c) Approved pharmaceutical contraceptive product (eg, birth control pills or patches, long-term injectable or implantable hormonal contraceptive)

    2. Intubated and mechanically-ventilated (patients who have had a tracheotomy may be considered as possible study participants as long as they are being mechanically ventilated)

    3. Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph

    4. Presence of Gram-negative organism(s) indicated by:
    a) Gram-stain OR
    b) Culture of pre-therapy respiratory specimen (eg, acceptable TA, BAL, mini-BAL, PSB) OR
    c) Suspected Gram-negative pathogen based on local surveillance data and medical history. Local surveillance data reflects the local patterns of bacterial prevalence and antibiotic resistance. Consideration should be given to the recent incidence of infections with Gram-negative organisms in the hospital

    5. Removed with amendment 5

    6. Impaired oxygenation (within 48 hours prior to screening): a PaO2/FiO2 ≤ 300 mmHg

    7. CPIS greater than or equal to 6, (Section 15.3)

    8. The presence of a MDR organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms (MDR organism: an organism resistant to representative agents in two or more of the following antibiotic classes - beta-lactams, including penicillins, cephalosporins, and monobactams; carbapenems; fluoroquinolones; and aminoglycosides):
    a) Antimicrobial therapy in the preceding two weeks
    b) Current hospitalization greater than or equal to 5 days
    c) High frequency (> 10%) of antibiotic resistance in the community or in the specific hospital unit
    d) Immunosuppressive disease and/or therapy
    e) Presence of the risk factors for HCAP
    • Hospitalization for two days or more in the preceding 90 days
    • Residence in a nursing home or extended care facility
    • Home infusion therapy (including antibiotics)
    • Chronic dialysis within 30 days
    • Home wound care
    • Family member with multidrug-resistant pathogen

    9. Be willing and able to give written informed consent. If the patient is unable to give written informed consent, the patient's authorized representative may may provide written consent as approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
    E.4Principal exclusion criteria
    1. A history of hypersensitivity to amikacin or other aminoglyosides,

    2. Has received systemic Gram-negative antibiotic therapy for greater than 48 hours at the time of administration of first dose of study drug. There should be as minimal a time delay as possible between randomization and first dose of study drug but up to 48 hours will be acceptable.
    Exceptions: Systemic antibiotic therapy for more than 48 hours for gram negative infection prior to administration of first dose of study drug is permitted if the infection is caused by pathogens that are resistant to the antimicrobial agent(s) used, or the patient's pneumonia is worsening.

    3. Has primary lung cancer (including patients with small cell lung carcinoma/non-small cell lung carcinoma and patients with unknown histology) or another malignancy metastatic to the lungs or other known endobronchial obstructions. Exception: Note that patients with complete
    resection of non-small cell lung carcinoma are eligible for the study.

    4. Known or suspected active tuberculosis, cystic fibrosis, human immunodeficiency virus (HIV) infection with CD 4 count < 200 cell/mm3 (HIV testing is not required as part of this protocol), or invasive fungal infection of the lung, lung abscess, or empyema.

    5. Known or suspected bacteremia secondary to Staphylococcus aureus

    6. Known or suspected neuromuscular disorders such as myasthenia gravis or parkinsonism

    7. Has had a stroke within five days. Additionally, patients with stroke in the acute or sub-acute phase should not be enrolled if at least one or both of the following apply:
    a) There is an increased risk of fatal brain edema as indicated by a history of hypertension or heart failure, major early computed tomography (CT) hypodensity exceeding 50% of the middle cerebral artery territory, and/or involvement of additional vascular territories.
    b) There is indication for deterioration based on comparison of patient's neurological condition within six hours of planned study drug dosing and patient's neurological condition two days before, judged by applying the National Institute of Health (NIH) Stoke Scale (Section 15.4).

    8. A positive urine and /or serum beta-human chorionic gonadotropin (B-hCG) pregnancy test

    9. Burns greater than 40% of total body surface area

    10. Patients with a serum creatinine > 2 mg/dL (177 μmol/L) Exception: Patients with a serum creatinine > 2 mg/dL (177 μmol/L) and being treated with continuous renal replacement therapy (continuous venovenous hemofiltration [CVVH] and continuous venovenous hemofiltration with dialysis [CVVH-D]) or daily hemodialysis will receive the aerosol study drug treatment (Section 8.4.6.1).

    11. Neutropenia (Screening absolute neutrophil count [ANC] < 103 neutrophils/mm3)

    12. Has been on mechanical ventilation for > 28 days (ie, current event should not be more than 28 continuous days). A patient is not considered extubated if cessation of mechanical ventilation lasts less than 24 hours.

    13. Is participating in or has participated in other investigational interventional studies within the previous 28 days

    14. The risk of rapidly fatal illness and death within 72 hours, or any concomitant conditions not related to VAP that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy.

    15. Stem cell transplantation

    16. Patients with documented Legionella infection (Legionella pneumonia)

    17. Has an APACHE II score < 10

    18. Previous assignment to treatment during this study

    19. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site)

    20. Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable will be Clinical Success in the mITT population (ie, the ITT population who prove to be culture positive for a Gram-negative pathogen and have an APACHE II score ≥ 10). Clinical Success is achieved when all of the following criteria are met:
    1) Systemic antibiotics (IV or by mouth [PO]) for pneumonia must be stopped on or before the Test-of-Cure (TOC) visit (Day 17-19)
    2) Systemic antibiotics (IV or PO) for pneumonia must not be restarted after the TOC visit
    3) The patient must survive through the late follow-up (LFU) visit
    4) The patient must not have a reported AE of lung abscess or empyema through the LFU visit and
    5) The patient must have stable respiratory function measured at the TOC visit
    E.5.1.1Timepoint(s) of evaluation of this end point
    TOC visit
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints:
    1. Pneumonia-related mortality to the LFU visit
    2. Early Clinical Response based on CPIS scores, the presence of empyema or lung abscess, and all-cause mortality through Day 10
    3. The number of days on mechanical ventilation through the LFU visit
    4. The number of ICU days assessed at the LFU visit

    The safety endpoints are to compare (BAY 41-6551 vs aerosolized placebo, as adjunctive therapy to IV antibiotics in both arms) as measured by:
    1. The frequency of AEs
    2. The progression and incidence rates of organ failure
    3. The all cause mortality rate during therapy, at Day 15 and at Day 28
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary efficacy endpoints:
    1: days 1-28.
    2: Days 1-10
    3: Day 28-32
    4: Day 28-32

    Safety endpoints:
    1, 2: throughout the study
    3: days 15 and at Day 28
    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) 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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 concerned3
    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
    Argentina
    Australia
    Brazil
    Canada
    Colombia
    Czech Republic
    Korea, Republic of
    Mexico
    Philippines
    Taiwan
    Thailand
    Turkey
    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
    The end of the study is defined as clean database
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    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 months9
    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 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.1.2.1Number of subjects for this age range: 278
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 84
    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 Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subjects that are intubated and mechanically-ventilated i.e. subjects that are typically in the intensive care units
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 234
    F.4.2.2In the whole clinical trial 362
    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)
    After the subject has ended his/her participation in the trial, he/she is treated according to local medical practice
    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 Decision2013-07-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-05-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-11-10
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