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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42732   clinical trials with a EudraCT protocol, of which   7035   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2004-002312-29
    Sponsor's Protocol Code Number:INOT-27
    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:2005-04-29
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2004-002312-29
    A.3Full title of the trial
    The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The Effects of Nitric Oxide for Inhalation on the Development of Chronic Lung Disease in Pre-term Infants.
    A.3.2Name or abbreviated title of the trial where available
    EUNO Preemie
    A.4.1Sponsor's protocol code numberINOT-27
    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 SponsorINO Therapeutics
    B.1.3.4CountryUnited States
    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 supportINO therapeutics
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINO therapeutics
    B.5.2Functional name of contact pointKristen Czech
    B.5.3 Address:
    B.5.3.1Street Address53 Frontage Road, third Floor
    B.5.3.2Town/ cityHampton, New Jersey
    B.5.3.3Post code08827
    B.5.3.4CountryUnited States
    B.5.4Telephone number19082386600
    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. name INO max® (Nitric Oxide) for inhalation (400 ppm)
    D. of the Marketing Authorisation holderINO Therapeutics AB, Sweden
    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 nameINO max® (Nitric Oxide) for inhalation (400 ppm)
    D.3.2Product code N/A
    D.3.4Pharmaceutical form Inhalation gas
    D.3.4.1Specific paediatric formulation Yes
    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 INNnitric oxide
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameN/A
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.04
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 Yes
    D. medicinal product typenitric oxide for inhalation
    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 placeboInhalation gas
    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
    prevention of chronic lung disease in pre-term infants ( gestational age < 29 weeks) with respiratory distress.
    E.1.1.1Medical condition in easily understood language
    prevention of chronic lung disease in in pre-born children ( gestational age < 29 weeks) with a shortness of breath.
    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 14.1
    E.1.2Level PT
    E.1.2Classification code 10054933
    E.1.2Term Neonatal respiratory distress syndrome prophylaxis
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the safety and efficacy of inhaled nitric oxide to reduce the risk of chronic lung disease in pre-term infants with respiratory distress and to assess the long term effects of the therapy on the development of these children over 7 years of clinical follow up.

    E.2.2Secondary objectives of the trial
    To assess:
    -number of days of assisted ventilation.
    -length of hospitalisation.
    -Survival without severe IVH, and PVL.
    - total number of days in-hospital from 36 weeks GA to one year and two years corrected age.
    - average number of days in-hospital for respiratory illness from 36 weeks GA to one year and two years corrected age.

    GA- gestational age
    IVH - intraventricular hemorrhage
    PVL - periventricular leukomalacia
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1) MRI Sub-Study INOT-27M (at selected centres only)
    The use of 40-week MRI scans to determine the effects of inhaled NO on the brain of premature infants:

    MRI brain imaging in preterm infants randomized to clinical study INOT-27 (The prevention of chronic lung disease in preterm infants (gestational age < 29 weeks) with respiratory distress)

    Objective: The primary objective is to determine the extent of brain abnormality using quantitative MRI measures in preterm infants (< 29 weeks GA) randomized into clinical study INOT-27, and to compare the extent of abnormality between infants treated with inhaled NO and those treated with placebo.

    The secondary objective will be to correlate the extent of MRI-defined brain abnormality with neurodevelopmental status at 2 years of age.

    2) Tracheal Aspirate Sub-Study INOT27-TA (at selected centres only) Inflammatory Mediators In Tracheal Aspirates Of Preterm Infants Participating In The Euno (INOT27) Study:

    Tracheal Aspirate Samples are collected on Days 2, 4, 7, 14 & 21 of the main Euno study. These are analysed in the INOT27TA Substudy.
    E.3Principal inclusion criteria
    The patient must meet the following criteria:

    Inborn preterm infants 24+0 weeks–28+6 days weeks gestational age (defined by first trimester ultrasound or if not available based on the last menstrual period) who requires the use of surfactant within 24 hours of birth, (either prophylactically or for signs of developing respiratory distress), or who requires the use of CPAP (FiO2 ≥ 0.30 and mean airway pressure ≥ 4cm H2O) within 24 hours of birth in order to maintain an SpO2 ≥ 85%.

    • Informed consent of the parent or legal guardian.

    CPAP = Continuous Positive Airway Pressure
    SpO2 = Oxygen saturation by pulse oximeter
    E.4Principal exclusion criteria
    - Outborn infants.
    - Infants ≥ 29 weeks gestational age.
    - Infants with birth weight <500 grams.
    - Infants requiring FiO2 >0.5 to maintain SpO2 >85%, on a sufficient mean airway pressure (e.g. > 8 cm H2O on CMV ) in order to achieve adequate chest inflation (8-9 ribs on Chest X-ray) two hours after the proper administration of exogenous surfactant.
    - Any suspected congenital heart disease other than patent ductus arteriosus or atrial septal defect.

    - Any infant with suspected lung hypoplasia associated with congenital diaphragmatic hernia

    - Any infant with severe bleeding or coagulation abnormalities at high-risk of diathesis, e.g., platelet <50,000/mm3, fibrinogen <0.5 g/L, other clotting factors <10%.

    - Any infant in whom a decision has been made not to provide full treatment, e.g., chromosomal abnormalities, severe multiple abnormalities, severe birth asphyxia, etc.
    - Use of another investigational drug or device before or during the active study period

    CMV = Controlled Mechanical Ventillation
    FiO2 = Fraction of inspired oxygen concentration

    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy Variable

    The primary efficacy variable for this study will be a binary endpoint determined by assessment at 36 week post-menstrual age (PMA). An infant who is alive without CLD at 36 PMA will be counted as a ‘success’. An infant who has died, or who has CLD at 36 weeks PMA will be counted as a ‘failure’.

    CLD is defined as the need for supplemental oxygen at 36 weeks post-menstrual age (based on a physiologic assessment).
    PMA = Post menstrual age
    CLD = chronic lung disease
    E.5.1.1Timepoint(s) of evaluation of this end point
    endpoint determined by assessment at 36 week post-menstrual age (PMA)
    E.5.2Secondary end point(s)
    The following will be assessed at 1 and 2 years corrected age and at 6-7 years of age:
    • Physical Examination including height and weight
    • Vital Signs
    • Concomitant Therapies (within 1 month of follow-up visit)
    • Concomitant Medication (within 1 month of follow-up visit)
    • Survival
    • Days of in-patient hospitalization in preceding interval
    • Days of in-patient hospitalization in preceding interval due to respiratory illness
    • Neurocognitive development (validated, age appropriate instrument) at 2 and 7 years of age ONLY
    o The assessment at 2 years corrected age will include assessment of three domains: cognitive, motor and sensory; the specific instruments will be the Bayley Scale of Infant Development (BSID-III), a structured neurologic examination (after Amiel-Tison 32), and an assessment of sensory development using a parent questionnaire (Nottingham questionnaire).
    o The assessment at age 7 will include assessment of three domains: cognitive, motor and behavior.
    E.5.2.1Timepoint(s) of evaluation of this end point
    will be assessed at 1 and 2 years corrected age and at 6-7 years of age
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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 Yes
    E.6.13.1Other scope of the trial description
    2 Sub-studies (MRI scan and Tracheal Aspirate)
    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. 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA35
    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 No
    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
    Study to include 7 years of clinical follow up in order to assess the long term effects on the development of the infant i.e. "2 years of recruitment and intervention, followed by 7 years of clinical follow-up”
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years9
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years9
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 800
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F. of subjects for this age range: 800
    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) No
    F.1.3Elderly (>=65 years) No
    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. of subjects incapable of giving consent
    pre-term infants (gestational age 24-28 weeks) with respiratory distress
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 800
    F.4.2.2In the whole clinical trial 800
    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)
    Follow up assessments made by study doctor to monitor progress of child at 1 and 2 years of age and again at 6-7 years of age.
    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 Decision2004-12-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-12-21
    P. End of Trial
    P.End of Trial StatusCompleted
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