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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39587   clinical trials with a EudraCT protocol, of which   6490   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).
     
    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:2017-003773-34
    Sponsor's Protocol Code Number:IT001-303
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-09-04
    Trial 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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2017-003773-34
    A.3Full title of the trial
    A prospective Phase 3, double-blind, multicenter, randomized study of the efficacy and safety of sulopenem followed by sulopenem etzadroxil with probenecid versus ertapenem followed by ciprofloxacin and metronidazole or amoxicillin-clavulanate for treatment of complicated intra-abdominal infections in adults.
    Prospektív, fázis III, kettős-vak, többközpontú, randomizált vizsgálat, amely a felnőttek komplikált intraabdominális fertőzéseinek kezelésére alkalmazott sulopenem és ertapenem hatékonyságát és biztonságosságát hasonlítja össze, úgy, hogy a kezelés folytatásaként vagy sulopenem etzadroxil/ probenicidet, vagy ciprofloxacint és metronidazolt, vagy amoxicillin-klavulánsavat alkalmaznak
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    To compare the efficacy of sulopenem followed by sulopenem etzadroxil with probenecid versus ertapenem followed by ciprofloxacin and metronidazole or amoxicillin-clavulanate for treatment of complicated intra-abdominal infection in adults, on Day 28 (test of cure [TOC]) post randomization.
    A sulopenem és az etrapenem hatékonyságának ill. biztonságosságának összehasonlítása felnőttek komplikált intraabdominális fertőzeinek kezelésében
    A.3.2Name or abbreviated title of the trial where available
    IT001-303
    A.4.1Sponsor's protocol code numberIT001-303
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03358576
    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 SponsorIterum Therapeutics International Limited
    B.1.3.4CountryIreland
    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 supportIterum Therapeutics International Limited
    B.4.2CountryIreland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPSI CRO AG
    B.5.2Functional name of contact pointMaciej Wos, project manager
    B.5.3 Address:
    B.5.3.1Street Address1 Sierpnia 6A
    B.5.3.2Town/ cityWarsaw
    B.5.3.3Post code02-134
    B.5.3.4CountryPoland
    B.5.4Telephone number+48507 081 702
    B.5.5Fax number+4822210 02 20
    B.5.6E-mailMaciej.wos@psi-cro.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.3.2Product code Sulopenem
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    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 INNSULOPENEM
    D.3.9.1CAS number 120788-07-0
    D.3.9.2Current sponsor codeCP-70,429
    D.3.9.4EV Substance CodeSUB10754MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 No
    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.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 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.3.2Product code Sulopenem etzadroxil/Probenecid
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNSULOPENEM ETZADROXIL
    D.3.9.1CAS number 1000296-70-7
    D.3.9.2Current sponsor codePF-03709270
    D.3.9.4EV Substance CodeSUB10754MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPROBENECID
    D.3.9.1CAS number 57-66-9
    D.3.9.4EV Substance CodeSUB10053MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 No
    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.IMP: 3
    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 Augmentin 875mg/125mg Film-Coated Tablets
    D.2.1.1.2Name of the Marketing Authorisation holderSmithKline Beecham Pharmaceuticals
    D.2.1.2Country which granted the Marketing AuthorisationRomania
    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 Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNAMOXICILLIN TRIHYDRATE and 125mg of CLAVULANIC ACID as POTASSIUM CLAVULANATA
    D.3.9.1CAS number 61336-70-7
    D.3.9.3Other descriptive nameAMOXICILLIN TRIHYDRATE
    D.3.9.4EV Substance CodeSUB00504MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number875
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCLAVULANIC ACID
    D.3.9.1CAS number 58001-44-8
    D.3.9.4EV Substance CodeSUB06642MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 No
    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.IMP: 4
    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 Ciprofloxacin STADA 500 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderSTADApharm 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 Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNCIPROFLOXACIN STADA
    D.3.9.1CAS number 0085721-33-1
    D.3.9.3Other descriptive nameCIPROFLOXACIN
    D.3.9.4EV Substance CodeSUB07470MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 No
    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.IMP: 5
    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 INVANZ® 1 g powder for concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    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 INNERTAPENEM SODIUM
    D.3.9.1CAS number 153773-82-1
    D.3.9.4EV Substance CodeSUB16424MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 No
    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.IMP: 6
    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 Metronidazole Nycomed 500mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderTakeda Pharma AS
    D.2.1.2Country which granted the Marketing AuthorisationEstonia
    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 Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNMETRONIDAZOLE
    D.3.9.1CAS number 0000443-48-1
    D.3.9.4EV Substance CodeSUB08922MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 No
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    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
    Complicated intra-abdominal infection
    komplikált intraabdominális fertőzések
    E.1.1.1Medical condition in easily understood language
    Complicated intra-abdominal infection
    komplikált intraabdominális fertőzések
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    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 efficacy of sulopenem followed by sulopenem etzadroxil with probenecid versus ertapenem followed by ciprofloxacin and metronidazole or amoxicillin-clavulanate for treatment of complicated intra-abdominal infection in adults, on Day 28 (test of cure [TOC]) post randomization.
    A felnőttek komplikált hasüregi fertőzéseinek kezelésére alkalmazott sulopenem, majd a kezelés folytatásaként sulopenem etzadroxil/ probenicid, illetve az ertapenem, majd a kezelés folytatásaként ciprofloxacin és vagy metronidazol, vagy amoxicillin-klavulánsav hatékonyságának és biztonságosságának összehasonlítása a randomizálást követő 28. napon (a gyógyulás ellenőrzése [TOC]).
    E.2.2Secondary objectives of the trial
    To compare the efficacy outcomes at other relevant time points as well as the safety profile of treatment with sulopenem followed by sulopenem etzadroxil plus probenecid versus ertapenem followed by ciprofloxacin and metronidazole or amoxicillin-clavulanate for treatment of complicated intra-abdominal infection in adults.

    To assess the population PK profile of sulopenem when administered either intravenously or as the prodrug, sulopenem etzadroxil, co-administered with probenecid.
    A felnőttek komplikált hasüregi fertőzéseinek kezelésére alkalmazott sulopenem, majd a kezelés folytatásaként sulopenem etzadroxil/ probenicid, illetve az ertapenem, majd a kezelés folytatásaként ciprofloxacin és vagy metronidazol, vagy amoxicillin-klavulánsav hatékonyságának és biztonságosságának összehasonlítása megfelelő időpontokban.
    A sulopenem populációs PK profiljának értékelése, ha a szert intravénásan, vagy ha prodrugját a sulopenem etzadroxilt probeneciddel együtt alkalmazzák
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    POPULATION PK SUBSTUDY
    Date and Version: August 22, 2018 Amendment #1

    This study will be conducted within the context of an ongoing Phase 3 sulopenem clinical trial in order to generate confirmatory data for the population PK profile of both the IV and oral pro-drug regimens of sulopenem.
    Populaciós farmakokinetika
    2018 Aug 22, protokoll amendment 1

    Igazoló adatok gyűjtése a az IV ill az orális kezelések populaciós farmakokinetikai profiljának kialakításához a vizsgálat keretében
    E.3Principal inclusion criteria
    1. Patient able to provide a signed written informed consent prior to any study-specific procedures.

    2. Adult patients ≥18 years of age

    3. EITHER:
    a. Intra-operative/post-operative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least 1 of the following diagnosed during the surgical intervention:
    i. Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall
    ii. Diverticular disease with perforation or abscess
    iii. Appendiceal perforation or peri-appendiceal abscess
    iv. Traumatic perforation of the intestines, only if operated on >12 hours after perforation occurs
    v. Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites)
    vi. Intra-abdominal abscess (including of liver or spleen provided that there was extension beyond the organ with evidence of intraperitoneal involvement).
    OR:
    b. Pre-operative enrollment where one of the following surgical procedures are planned within 24 hours of the first dose of study drug:
    i. Open laparotomy, percutaneous drainage of an intra-abdominal abscess, or laparoscopic surgery.

    4. Evidence of systemic inflammatory indicators, with at least one of the following:
    a. Fever (defined as body temperature >38°C) or hypothermia with a core body temperature <35°C
    b. Elevated white blood cell count (>12,000 cells/mm3) or leukopenia (defined as white blood cell count <4,000 cells/mm3)
    c. Drop in blood pressure (systolic BP must be <90 mmHg without pressor support)
    d. Increased heart rate (>90 bpm) and respiratory rate (>20 breaths/min)
    e. Hypoxia (oxygen saturation ≤90 percent on room air)

    5. Physical findings or symptoms consistent with intra-abdominal infection, with at least one of the following:
    a. Abdominal pain and/or tenderness, with or without rebound
    b. Localized or diffuse abdominal wall rigidity
    c. Abdominal mass
    d. Nausea and/or vomiting
    e. Altered Mental Status

    6. Specimen/s from the surgical intervention were sent or planned to be sent for culture.

    Microbiologic specimens collected during routine operative care prior to subject providing informed consent may be used for study purposes.
    1. A beteg képes aláírni a betegtájékoztatót és beleegyező nyilatkozatot még mielőtt bármilyen vizsgálattal kapcsolatos eljárásra sor kerülne.
    2. A beteg felnőtt korú, azaz ≥18 éves.
    3. VAGY:
    a. Intra-operatív/poszt-operatív bevonás a hashártyagyulladással kapcsolatos hasüregi fertőzés látható jele alapján (gennygyülem van a hasüregben), többek között, ha az alábbiak legalább egyikét diagnosztizálják a műtéti beavatkozás során:
    i. Gangrénás ruptúrával kísért vagy perforált, vagy az epehólyag falát áttörő fertőzéssel jelentkező epehólyag gyulladás
    ii. Perforációval, vagy tályoggal járó divertikulitisz
    iii. Perforált vakbél, vagy vakbélkörnyéki tályog
    iv. Trauma okozta bélperforáció, ha a műtétre a perforációt követően több, mint 12 órával kerül sor
    v. Szekunder hashártyagyulladás (de nem májcirózissal és krónikus ascitessel járó spontán bakteriális hashártyagyulladás)
    vi. Hasüregi tályog (ideértve a májat vagy lépet érintő tályogot, feltéve, hogy az a szerven kívülre is terjedt, és bizonyítottan fennáll az intraperitoneális érintettség).
    VAGY:
    b. Pre-operatív bevonás, ha az alábbi műtéti eljárások valamelyikét tervezik elvégezni a vizsgálati készítmény első dózisát megelőző 24 órán belül:
    i. Nyílt laparotómia, a hasüregi tályog perkután drenázsa, vagy laparoszkópos műtét
    4. Kimutathatók a szisztémás gyulladás paraméterei, azaz, az alábbiak közül legalább egy jelen van:
    a. Láz (38°C-nál magasabb testhőmérséklet) vagy hypotermia, amikor a maghőmérséklet kevesebb, mint 35°C
    b. Emelkedett fvs (>12,000 sejt/mm3), vagy leukopénia (fvs <4,000 sejt/mm3)
    c. Vérnyomásesés (a szisztolés érték kevesebb, mint 90 Hgmm vérnyomástámogatás nélkül)
    d. Emelkedett pulzus (>90/perc) és légzésszám (>20 /perc)
    e. Hypoxia (az oxigén szaturációja ≤90 % szobalevegőn)
    5. A hasüregi fertőzés fizikális jelei:
    a. Hasi fájdalom és/vagy érzékenység visszacsapással (rebound), vagy anélkül
    b. Lokalizáltan, vagy diffúzan merev hasfal
    c. Hasi térfoglalás (abdominal mass)
    d. Hányinger és/vagy hányás
    e. Megváltozott mentális állapot
    6. A műtéti beavatkozáskor vett mintát, vagy mintákat elküldték tenyésztésre (vagy pre-operatív bevonás esetén tervezik ezek elküldését).
    A vizsgálat céljaira felhasználhatók azok a mikrobiológiai minták is, amelyeket a rutin műtéti ellátás során vettek, még azt megelőzően, hogy a beteg aláírta volna a betegtájékoztatót és beleegyező nyilatkozatot.
    E.4Principal exclusion criteria
    1. Patient diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which the primary etiology was not likely to be infectious.
    2. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
    3. Patient has simple cholecystitis or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess.
    4. Patient whose surgery included staged abdominal repair, or “open abdomen” technique, or marsupialization.
    5. Patient known at study entry to have a complicated intra-abdominal infection caused by pathogens non-susceptible to the study antimicrobial agents.
    6. Patient needed effective concomitant systemic antibacterials or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected MRSA or Enterococcus spp.
    7. Patient has perinephric infections or an indwelling peritoneal dialysis catheter.
    8. Patient has suspected intra-abdominal infections due to fungus, parasites, virus, or tuberculosis.
    9. Patient with known history of serious allergy, hypersensitivity or any serious reaction to carbapenem antibiotics, other β-lactam antibiotics, quinolones, metronidazole, or probenecid, as formulated with their excipients.
    10. Patient known to have any of the following laboratory values as defined below:
    a. Hematocrit <25% or hemoglobin <8 g/dL
    b. Absolute neutrophil count <1000/mm3
    c. Platelet count <75,000/mm3
    d. Bilirubin >3 x the ULN, unless isolated hyperbilirubinemia was directly related to the acute infection or known Gilbert’s disease
    e. ALT or AST >3 x ULN values at Screening. Patients with elevations of AST and/or ALT up to 5 x ULN will be eligible if these elevations are acute and directly related to the infectious process being treated. This must be documented
    f. ALP >3 x ULN. Patients with values >3.0 x ULN and <5.0 x ULN are eligible if this value is acute and directly related to the infectious process being treated. This must be documented.
    11. Patient has a body mass index >45 kg/m2.
    12. Patient has APACHE II score >30 (serum bicarbonate may be used in place of arterial blood gases).
    13. Patient considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness, including septic shock that was associated with a high risk of mortality.
    14. Patient unlikely to respond to 10–14 days of treatment with antibiotics.
    15. Patient received systemic antibacterial agents within the 72-hour period prior to study entry, unless either of the following pertained:
    a. Patient has new infection (not considered a treatment failure) and both of the following were met:
    i. Patient received no more than 24 hours of total prior antibiotic therapy
    ii. Patient received ≤1 dose of a treatment regimen post-operatively and antibiotics were not received more than 6 hours post-procedure.
    b. Patient considered to have failed previous treatment regimen i.e., pre-operative treatment of any duration with non-study systemic antimicrobial therapy for peritonitis or abscess permitted provided that all of the following are met:
    i. The treatment regimen had been administered for at least 72 hours and judged to have been inadequate
    ii. The patient had an operative intervention that was just completed or was intended no more than 24 hours after study entry
    iii. Findings of infection were documented at surgery
    iv. Specimens for bacterial cultures and susceptibility testing were taken at operative intervention
    16. Patient has concurrent infection that interfere with the evaluation of response to the study antibiotic.
    17. Patient receiving hemodialysis, hemofiltration, or peritoneal dialysis.
    18. Patient has history of acute hepatitis in the recent past (3 months prior to study entry), chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure.
    19. Patient has past or current history of epilepsy or seizure disorders excluding febrile seizures of childhood.
    20. Patient immunocompromised as evidenced by any of the following:
    a. HIV infection, with either a recent (in the past 6 months) acquired immune deficiency syndrome-defining condition or a CD4 + T lymphocyte count <200/mm3
    b. Systemic or hematological malignancy requiring chemotherapeutic or radiologic/immunologic interventions within 6 weeks prior to randomization, or anticipated to begin prior to completion of study
    c. Immunosuppressive therapy, including maintenance corticosteroid therapy (>40 mg/day equivalent prednisolone for 5 days or more).
    21. Patient has known inflammatory bowel disease (ulcerative colitis or Crohn’s disease) or Clostridium difficile-associated diarrhea.
    22. Patients with history of blood dyscrasias
    1.Olyan traumás bélperforáció, amikor a beteget 12 órán belül megoperálták; gyomor-nyombélfekély perforáció, amelyet 24 órán belül műtöttek. .
    2.A betegnél hasfali tályog, vagy perforáció nélküli bélelzáródás, vagy perforáció nélküli iszkémiás bélgyulladás áll fenn.
    3.Egyszerű, vagy gangrénás epehólyag gyulladás ruptúra nélkül, vagy egyszerű vakbélgyulladás, vagy akut, gennyes epeúti gyulladás, vagy elfertőzött, nekrotizáló hasnyálmiriggyulladás, vagy hasnyálmirigy tályog fennállása.
    4.Ha a betegnél a műtét fokozatos hasi helyereállító műtétet, vagy „nyitott” hasi műtéti technikát, vagy marsupializációt foglalt magába.
    5.Ha a vizsgálatba választásnál tudott, hogy a beteg komplikált hasüregi fertőzését a vizsgálatban alkalmazott antimikrobás szerekre nem érzékeny kórokozók okozták.
    6.A beteg a két vizsgálati csoportban meghatározott készítményeken kívül más, hatékony kiegészítő szisztémás antibakteriális (orális, iv, vagy intramuszkuláris), illetve antifungális kezelésre szorult, kivéve, ha ismert, vagy gyanított methicillin-rezisztens Staphylococcus aureus (MRSA), vagy Enterococcus spp. fertőzése kezelésére vancomycint, linezolidot, vagy daptomycint kezdtek el adni.
    7.A betegnek perinefrikus fertőzései vannak, vagy hashártya dialízisre szolgáló katétert visel.
    8.A betegnek gyaníthatóan gomba, parazita (például amőbás májtályog), vírus, vagy tbc okozta hasüregi fertőzése van.
    9.A beteg kórtörténetében súlyos allergia, túlérzékenység, vagy bármiféle súlyos gyógyszerreakció fordult elő karbapenem antibiotikum, vagy más ß-laktám antibiotikum, quinolonok, metronidazol, vagy probenecid és ezek segédanyagainak alkalmazásakor.
    10.A betegnél az alábbi laborparaméterek valamelyike áll fenn:
    a. Hematokrit <25% vagy hemoglobin <8 g/dl
    b. Abszolút neutrofil szám <1000/mm3
    c. Vérlemezke szám <75,000/mm3
    d. A bilirubin a normál tartomány felső értékének (ULN) több mint háromszorosa, kivéve, ha az izolált hyperbilirubinemia közvetlen kapcsolatban állt az akut fertőzéssel, vagy ha a betegnek Gilbert kórja van.
    e. Az alanin aminotranszferáz (ALT) vagy aszpartát aminotranszferáz (AST) >3 x ULN a szűréskor. Az AST és/vagy ALT több mint ötszörös ULN értéke nem számít kizáró kritériumnak, ha ez az emelkedés akut, és közvetlen kapcsolatban áll az éppen kezelt fertőzéses folyamattal. Ezt a tényt dokumentumokkal kell alátámasztani.
    f. Az alkáli foszfatáz (ALP) >3 x ULN. Beválasztható a >3.0 x ULN és <5.0 x ULN beteg, ha ez az emelkedés akut, és közvetlen kapcsolatban áll az éppen kezelt fertőzéses folyamattal. Ezt a tényt dokumentumokkal kell alátámasztani.
    11.A beteg testtömeg indexe >45 kg/m2.
    12.A beteg APACHE II száma >30 (artériás vérgáz érték helyett a szérum bikarbonáté is megfelel
    13.A beteg várhatóan nem él addig, hogy leteljen a 4 hetes vizsgálati időszak,
    14.A beteg feltehetően nem fog reagálni a 10–14 napos antibiotikumos kezelésre.
    15.A beteg szisztémás antibakteriális szereket kapott a vizsgálatba való belépést megelőző 72 órában, hacsak nem állt fenn az alábbiak valamelyike:
    a. A betegnek új fertőzése van (nem tekinthető sikertelen kezelésnek), és mindkét alábbi feltétel teljesült:
    i. Az előzetes antibiotikumos terápia összesen nem haladta meg a 24 órát
    ii. A beteg ≤1 dózisnyi gyógyszert kapott a posztoperatív szakaszban, és nem kapott antibiotikumot a műtéti beavatkozást követő 6 órán túl.
    b. A beteg előző kezelését sikertelennek tekintik, azaz a hashártyagyulladás, vagy tályog bármilyen időtartamú műtét előtti szisztémás, a vizsgálaton kívüli antimikrobiális szerrel történt kezelése megengedett, ha az alábbiak teljesülnek:
    i. A kezelést legalább 72 órán át kapta a beteg, és az nem volt eredményes.
    ii. A beteg műtéti beavatkozáson esett át, amely épp befejeződött, vagy műtéti beavatkozást terveznek a vizsgálatba való belépést követő 24 órában.
    iii. A fertőzést a sebészeti beavatkozás során dokumentálták
    iv. A mintákat vettek baktériumtenyésztésre és érzékenységi vizsgálatra.
    v. A randomizálás után nem alkalmaztak további, antibakteriális készítményeket.
    16. A betegnek egyidejűleg másik fertőzése is van,
    17. A beteg hemodialízisben, hemofiltrációban, vagy hashártya dialízisben részesül.
    18. A beteg kórtörténetében a közelmúltban akut vagy krónikus hepatitis, májcirrhosis, akut vagy a krónikus májelégtelenség akut dekompenzációja .
    19. A beteg régebbivagy jelenlegi betegségei közt szerepel az epilepszia, vagy görcsrohamok
    20. A beteg immunrendszere csökkent védekezőképességgel rendelkezik,
    a. Humán immunhiányos vírus fertőzés,
    b. Rosszindulatú szisztémás, vagy hematológiai elváltozás,
    c. Immunszuppressziós terápia, ideértve a fenntartó kortikoszteroid terápiát is 21.A beteg valamely más klinikai vizsgálatban vesz részt,
    22. A beteg olyan helyzetben, vagy állapotban van, hogy az a vizsgálóorvos megítélése szerint befolyásolhatja azt, hogy részvétele a vizsgálatban optimális lehessen.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome measure for efficacy evaluation on Day 28 will be the resolution of the symptoms of cIAI present at trial entry.

    A patient’s outcome will be programmatically defined as a clinical cure if the following criteria are met:
    • Patient is alive
    • Resolution of baseline signs and symptoms of the index infection
    o No new symptoms
    • No new antibiotics or interventions for treatment failure are required

    Clinical failure, defined as:
    • death due to cIAI
    • Surgical site wound infection requiring non-study systemic antibiotic therapy
    • Unplanned surgical procedures or percutaneous drainage procedures for complication or recurrence of cIAI based on documented worsening symptoms or signs of cIAI
    • Initiation of non-trial antibacterial drug therapy for treatment of cIAI based on documented worsening symptoms or signs of cIAI

    If data are unavailable to determine if the patient is a cure or a failure, the patient outcome will be considered an indeterminate response.

    For the primary efficacy evaluation, the proportions of patients achieving cure, failure or indeterminate will be determined in the microbiologic-modified intent to treat population (m-MITT). The m-MITT population will be comprised of all randomized patients who received at least one dose of study drug and had a baseline pathogen causing cIAI isolated from a culture specimen taken at baseline, prior to initiation of study drug therapy.
    A klinikai válaszreakció értékeléséhez hozzátartozik a cIAI alábbi jeleinek és tüneteinek megítélése: láz, leukocitózis, szisztolés vérnyomás, pulzus, légzésszám, oxigén szaturáció, hasi fájdalom, vagy érzékenység, hasi térfoglalás, megváltozott elmeállapot, hányinger és hányás.
    A mikrobiológiai válaszreakció megítélése a sebészeti beavatkozáskor levett minták tenyésztése alapján történik
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary outcome measure for efficacy evaluation on Day 28
    Az elsődleges értékelés a 28. napon
    E.5.2Secondary end point(s)
    Same clinical endpoint as the primary endpoint but at EOT instead of TOC/day 28.
    Ugyanazuok a végpontok, mint az elsődleges de a vizsgálat végén nem a kezelés végén/28. napon
    E.5.2.1Timepoint(s) of evaluation of this end point
    TOC/day 28.
    kezelés vége/28. nap
    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 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) Yes
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Bulgaria
    Czech Republic
    Estonia
    Georgia
    Hungary
    Latvia
    Poland
    Russian Federation
    Serbia
    Ukraine
    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
    LVLS
    utolsó beteg utolsó vizitje
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    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.1.2.1Number of subjects for this age range: 469
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 201
    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 No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    This includes patients in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, institutionalised, or mentally handicapped.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state46
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 341
    F.4.2.2In the whole clinical trial 670
    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)
    none
    nincs
    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 Decision2018-10-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-10-02
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA