<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03235986</url>
  </required_header>
  <id_info>
    <org_study_id>CCD-01534CA1-01</org_study_id>
    <secondary_id>2016-004547-36</secondary_id>
    <nct_id>NCT03235986</nct_id>
  </id_info>
  <brief_title>A Study To InvestigateThe Safety, Tolerability And Efficacy Of Nebulised Curosurf® In Preterm Neonates With Respiratory Distress Syndrome (RDS)</brief_title>
  <official_title>A Randomized, Open, Multinational, Multicentre,2-Part Study In Spontaneously Breathing Preterm Neonates With Mild To Moderate Respiratory Distress Syndrome (RDS) To Investigate The Safety, Tolerability And Efficacy Of Inhaled Nebulised Poractant Alfa (Porcine Surfactant, Curosurf®) In Comparison With Nasal Continuous Positive Airway Pressure (nCPAP) Alone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chiesi Farmaceutici S.p.A.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will mainly aim at investigating the safety, tolerability and efficacy of&#xD;
      different escalating single doses administration of nebulised Curosurf®, in preterm neonates&#xD;
      with RDS (Respiratory Distress Syndrome) during nCPAP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be conducted in spontaneously breathing preterm neonates with mild to moderate&#xD;
      RDS and will consist of two parts:&#xD;
&#xD;
      Part I, with the objective to assess the safety and tolerability of single ascending doses of&#xD;
      nebulised Curosurf® ; Part II, with the objective to compare the efficacy of nebulised&#xD;
      Curosurf®, administered at two selected doses from part I, during nCPAP, versus nCPAP alone&#xD;
      in terms of incidence of respiratory failure in the first 72 hours of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Change in the benefit-risk balance&#xD;
  </why_stopped>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">May 5, 2020</completion_date>
  <primary_completion_date type="Actual">May 5, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Part I is an ascending dose scheme of IMP versus nCPAP alone. Part II is a parallel group with 2 doses of IMP versus nCPAP alone. In part II, one additional dose may be administered between 3 and 12 hours after the start of the first dose.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of neonates with respiratory failure</measure>
    <time_frame>in the first 72 hours of life</time_frame>
    <description>Respiratory failure defined as: need for endotracheal surfactant administration and/or mechanical ventilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>discharge or 36 weeks post menstrual age (PMA), whichever comes first</time_frame>
    <description>Any untoward medical occurrence in a clinical trial neonate administered a medicinal product and which does not necessarily have a casual relationship with the treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Drug Reactions</measure>
    <time_frame>discharge or 36 weeks post menstrual age (PMA), whichever comes first</time_frame>
    <description>Any untoward and unintended responses to an investigational product related to any dose administered</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">166</enrollment>
  <condition>Neonatal Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>nCPAP+ Nebulised Curosurf®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Curosurf® administered through nebulization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nCPAP alone (control)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Standard of care, respiratory support used also during experimental arms</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I)</intervention_name>
    <description>Single ascending doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part I)</description>
    <arm_group_label>nCPAP+ Nebulised Curosurf®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II)</intervention_name>
    <description>Two doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part II)</description>
    <arm_group_label>nCPAP+ Nebulised Curosurf®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I)</intervention_name>
    <description>Nasal continuous positive airway pressure alone</description>
    <arm_group_label>nCPAP alone (control)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II)</intervention_name>
    <description>nasal continuous positive airway pressure alone</description>
    <arm_group_label>nCPAP alone (control)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent obtained by parents/legal representative (according to local&#xD;
             regulation) prior to or after birth&#xD;
&#xD;
          2. Inborn neonates from 28+0 to 32+6 weeks of gestational age (GA), spontaneously&#xD;
             breathing and stabilised on nCPAP&#xD;
&#xD;
          3. Clinical course consistent with RDS.&#xD;
&#xD;
          4. Receiving CPAP pressure 5-8 centimeter of water (cm H2O) and fraction of inspired&#xD;
             oxygen (FiO2) between 0.25 and 0.40 to maintain saturation of peripheral oxygen (SpO2)&#xD;
             between 88% and 95% for at least 30 minutes. Randomization should occur between 60&#xD;
             minutes and 12 hours after birth.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Early need for endotracheal intubation for cardiopulmonary resuscitation in delivery&#xD;
             room or within 1 hour from birth because of severe RDS&#xD;
&#xD;
          2. Respiratory Distress not secondary to surfactant deficiency&#xD;
&#xD;
          3. Use of surfactant prior to study entry and need for endotracheal administration of any&#xD;
             other treatment.&#xD;
&#xD;
          4. Major congenital anomalies.&#xD;
&#xD;
          5. Evidence of severe birth asphyxia&#xD;
&#xD;
          6. Mothers with prolonged rupture of the membranes&#xD;
&#xD;
          7. Presence of air leaks.&#xD;
&#xD;
          8. Presence of IVH (intraventricular hemorrhage ) ≥ III.&#xD;
&#xD;
          9. Hypotension or evidence of hemodynamic instability.&#xD;
&#xD;
         10. Any condition that, in the opinion of the Investigator, would place the neonate at&#xD;
             undue risk.&#xD;
&#xD;
         11. Participation in another clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Weeks</minimum_age>
    <maximum_age>32 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlo Dani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Careggi Hospital, Florence (Italy)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prof.Carlo Dani, Coordinating Investigator - Careggi Hospital, Florence (Italy)</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004547-36/results</url>
    <description>Study Record on EU Clinical Trials Register including results</description>
  </link>
  <results_reference>
    <citation>Dani C, Talosi G, Piccinno A, Ginocchio VM, Balla G, Lavizzari A, Stranak Z, Gitto E, Martinelli S, Plavka R, Krolak-Olejnik B, Lista G, Spedicato F, Ciurlia G, Santoro D, Sweet D; CURONEB Study Group. A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome. J Pediatr. 2022 Jul;246:40-47.e5. doi: 10.1016/j.jpeds.2022.02.054. Epub 2022 Mar 5.</citation>
    <PMID>35257740</PMID>
  </results_reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>March 16, 2022</last_update_submitted>
  <last_update_submitted_qc>March 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Hyaline Membrane Disease</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Poractant alfa</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03235986
org study id: CCD-01534CA1-01
secondary id: 2016-004547-36
nct id: NCT03235986
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The present study will mainly aim at investigating the safety, tolerability and efficacy of
      different escalating single doses administration of nebulised Curosurf®, in preterm neonates
      with RDS (Respiratory Distress Syndrome) during nCPAP.
The study will be conducted in spontaneously breathing preterm neonates with mild to moderate
      RDS and will consist of two parts:

      Part I, with the objective to assess the safety and tolerability of single ascending doses of
      nebulised Curosurf® ; Part II, with the objective to compare the efficacy of nebulised
      Curosurf®, administered at two selected doses from part I, during nCPAP, versus nCPAP alone
      in terms of incidence of respiratory failure in the first 72 hours of life.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Part I is an ascending dose scheme of IMP versus nCPAP alone. Part II is a parallel group with 2 doses of IMP versus nCPAP alone. In part II, one additional dose may be administered between 3 and 12 hours after the start of the first dose.
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of neonates with respiratory failure
time frame: in the first 72 hours of life
description: Respiratory failure defined as: need for endotracheal surfactant administration and/or mechanical ventilation
measure: Adverse Events
time frame: discharge or 36 weeks post menstrual age (PMA), whichever comes first
description: Any untoward medical occurrence in a clinical trial neonate administered a medicinal product and which does not necessarily have a casual relationship with the treatment
measure: Adverse Drug Reactions
time frame: discharge or 36 weeks post menstrual age (PMA), whichever comes first
description: Any untoward and unintended responses to an investigational product related to any dose administered
arm group label: nCPAP+ Nebulised Curosurf®
arm group type: Experimental
description: Curosurf® administered through nebulization
arm group label: nCPAP alone (control)
arm group type: Other
description: Standard of care, respiratory support used also during experimental arms
intervention type: Drug
intervention name: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I)
description: Single ascending doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part I)
arm group label: nCPAP+ Nebulised Curosurf®
intervention type: Drug
intervention name: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II)
description: Two doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part II)
arm group label: nCPAP+ Nebulised Curosurf®
intervention type: Other
intervention name: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I)
description: Nasal continuous positive airway pressure alone
arm group label: nCPAP alone (control)
intervention type: Other
intervention name: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II)
description: nasal continuous positive airway pressure alone
arm group label: nCPAP alone (control)
criteria: 
gender: All
minimum age: 28 Weeks
maximum age: 32 Weeks
healthy volunteers: No
last name: Carlo Dani, MD
role: Principal Investigator
affiliation: Careggi Hospital, Florence (Italy)
facility: 
country: Italy
url: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004547-36/results
description: Study Record on EU Clinical Trials Register including results
citation: Dani C, Talosi G, Piccinno A, Ginocchio VM, Balla G, Lavizzari A, Stranak Z, Gitto E, Martinelli S, Plavka R, Krolak-Olejnik B, Lista G, Spedicato F, Ciurlia G, Santoro D, Sweet D; CURONEB Study Group. A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome. J Pediatr. 2022 Jul;246:40-47.e5. doi: 10.1016/j.jpeds.2022.02.054. Epub 2022 Mar 5.
PMID: 35257740
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Hyaline Membrane Disease
mesh term: Syndrome
mesh term: Poractant alfa
sharing ipd: No