<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/NCT03275415</url>
  </required_header>
  <id_info>
    <org_study_id>N201705026</org_study_id>
    <nct_id>NCT03275415</nct_id>
  </id_info>
  <brief_title>Intratracheal Budesonide/Surfactant Prevents BPD</brief_title>
  <official_title>Routine Administration of Surfactant/Budesonide to Prevent BPD in VLBW With RDS-A Double Blind Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taipei Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Taipei Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taipei Veterans General Hospital, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mackay Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seventh Medical Center of PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangzhou Women and Children's Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taichung Veterans General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Taipei Medical University</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>
      A double-blind study includes: 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after&#xD;
      birth and requires resuscitation 3) failure to NCPAP within 4 hrs after birth, defined as: a)&#xD;
      FIO2 ≥ 0.30, pressure &gt; 5cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion&#xD;
      criteria: 1) lethal cardiopulmonary status 2) severe congenital anomalies.&#xD;
&#xD;
      Given the COVID19 pandemics, the recruitment became difficult. Under the consideration of&#xD;
      scientific and practical consideration, we therefore determine to have a sample of 300, (150&#xD;
      in each group), fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and&#xD;
      with an expectation of 30 % improvement of primary outcome (from 60 % in control group to 40&#xD;
      % in the intervention group as original presumed).Appropriate amount of placebo will be used&#xD;
      as it does not affect the biophysical property of curosurf (PAS abstract 2017 San Francisco).&#xD;
      Primary outcome of study is death or BPD defined by NICHD criteria. Follow up study of&#xD;
      neuromotor and cognitive function and pulmonary states will be done at 1-2 years of corrected&#xD;
      age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A double-blind study will be conducted in 7 tertiary centers. Inclusion criteria are: 1)&#xD;
      birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation&#xD;
      3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure &gt; 5cmH2O&#xD;
      b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion criteria: 1) lethal&#xD;
      cardiopulmonary status 2) severe congenital anomalies.&#xD;
&#xD;
      The initial sample size was determined based on the expectation of 30% improvement of the&#xD;
      primary outcome (BPD/death) in the intervention group (Curosurf + budesonide) (40%), as&#xD;
      compared to control group (Curosurf +saline placebo) (60%), specifying a type I error of 0.05&#xD;
      and type II error 0.20. The total number needed was 240 (120 in each group). The study was&#xD;
      started in June 2019 before the pandemic of COVID19 and the study went on smoothly in 2019.&#xD;
      Because of the smooth enrollment of the patients in 2019, we decided to increase the ability&#xD;
      of the study for detecting the intervention effect through increasing the power from 80 % to&#xD;
      90 % (type II error from 0.2 to 0.1 and type I error decreased from 0.05 to 0.02). The total&#xD;
      sample size required was estimated to be 350 (170 in each group). Given the COVID19&#xD;
      pandemics, the recruitment became difficult. Under the consideration of scientific and&#xD;
      practical consideration, we therefore determine to have a sample of 300, (150 in each group),&#xD;
      fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and with an&#xD;
      expectation of 30 % improvement of primary outcome (from 60 % in control group to 40 % in the&#xD;
      intervention group as original presumed). The changes in sample size had been approved by&#xD;
      independent monitoring committee. We expect that the study will be completed in September&#xD;
      2022.&#xD;
&#xD;
      The sample will be stratified based on birth weight (500-749 grams, 750-999 grams and&#xD;
      1000-1499 grams), the presence of clinical chorioamnionitis or not, and site of study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2019</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>Phase 4</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>This is a double blind randomized trial. The infants will be randomly assigned into 2 groups: Control (C) (curosurf + saline) and Intervention (I) (curosurf+ budesonide).</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>This is a double blind randomized trial. The infants will be randomly assigned into 2 groups: Control (C) (curosurf + saline) and Intervention (I) (curosurf+ budesonide).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>incidence of death or BPD</measure>
    <time_frame>6 months</time_frame>
    <description>Primary outcome of study is death or BPD defined by NICHD criteria.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">310</enrollment>
  <condition>Respiratory Distress Syndrome</condition>
  <condition>Bronchopulmonary Dysplasia</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Curosurf + budesonide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Curosurf + saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>budesonide</intervention_name>
    <description>Intra-tracheal instillation of a combination of budesonide/surfactant in preterm infants with RDS to prevent BPD</description>
    <arm_group_label>Experimental</arm_group_label>
    <other_name>pulmicort</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Intra-tracheal instillation of a combination of saline/surfactant in preterm infants with RDS to prevent BPD</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>sodium chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1) birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires&#xD;
             resuscitation, 3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥&#xD;
             0.30, pressure &gt; 5 cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) lethal cardiopulmonary status, 2) severe congenital anomalies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Minutes</minimum_age>
    <maximum_age>4 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tsu F Yeh, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maternal Child Health Research Center, Taipei Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <results_reference>
    <citation>Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.</citation>
    <PMID>26351971</PMID>
  </results_reference>
  <results_reference>
    <citation>Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, Pyati S, Tsai CH. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008 May;121(5):e1310-8. doi: 10.1542/peds.2007-1973. Epub 2008 Apr 21.</citation>
    <PMID>18426851</PMID>
  </results_reference>
  <results_reference>
    <citation>Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr. 2010 Apr;156(4):537-41. doi: 10.1016/j.jpeds.2009.10.049. Epub 2010 Feb 6.</citation>
    <PMID>20138301</PMID>
  </results_reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 25, 2023</last_update_submitted>
  <last_update_submitted_qc>May 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BPD</keyword>
  <keyword>surfactant</keyword>
  <keyword>budesonide</keyword>
  <keyword>respiratory distress syndrome</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>Bronchopulmonary Dysplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</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/NCT03275415
org study id: N201705026
nct id: NCT03275415
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A double-blind study includes: 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after
      birth and requires resuscitation 3) failure to NCPAP within 4 hrs after birth, defined as: a)
      FIO2 ≥ 0.30, pressure > 5cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion
      criteria: 1) lethal cardiopulmonary status 2) severe congenital anomalies.

      Given the COVID19 pandemics, the recruitment became difficult. Under the consideration of
      scientific and practical consideration, we therefore determine to have a sample of 300, (150
      in each group), fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and
      with an expectation of 30 % improvement of primary outcome (from 60 % in control group to 40
      % in the intervention group as original presumed).Appropriate amount of placebo will be used
      as it does not affect the biophysical property of curosurf (PAS abstract 2017 San Francisco).
      Primary outcome of study is death or BPD defined by NICHD criteria. Follow up study of
      neuromotor and cognitive function and pulmonary states will be done at 1-2 years of corrected
      age.
A double-blind study will be conducted in 7 tertiary centers. Inclusion criteria are: 1)
      birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation
      3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure > 5cmH2O
      b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion criteria: 1) lethal
      cardiopulmonary status 2) severe congenital anomalies.

      The initial sample size was determined based on the expectation of 30% improvement of the
      primary outcome (BPD/death) in the intervention group (Curosurf + budesonide) (40%), as
      compared to control group (Curosurf +saline placebo) (60%), specifying a type I error of 0.05
      and type II error 0.20. The total number needed was 240 (120 in each group). The study was
      started in June 2019 before the pandemic of COVID19 and the study went on smoothly in 2019.
      Because of the smooth enrollment of the patients in 2019, we decided to increase the ability
      of the study for detecting the intervention effect through increasing the power from 80 % to
      90 % (type II error from 0.2 to 0.1 and type I error decreased from 0.05 to 0.02). The total
      sample size required was estimated to be 350 (170 in each group). Given the COVID19
      pandemics, the recruitment became difficult. Under the consideration of scientific and
      practical consideration, we therefore determine to have a sample of 300, (150 in each group),
      fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and with an
      expectation of 30 % improvement of primary outcome (from 60 % in control group to 40 % in the
      intervention group as original presumed). The changes in sample size had been approved by
      independent monitoring committee. We expect that the study will be completed in September
      2022.

      The sample will be stratified based on birth weight (500-749 grams, 750-999 grams and
      1000-1499 grams), the presence of clinical chorioamnionitis or not, and site of study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a double blind randomized trial. The infants will be randomly assigned into 2 groups: Control (C) (curosurf + saline) and Intervention (I) (curosurf+ budesonide).
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
masking description: This is a double blind randomized trial. The infants will be randomly assigned into 2 groups: Control (C) (curosurf + saline) and Intervention (I) (curosurf+ budesonide).
measure: incidence of death or BPD
time frame: 6 months
description: Primary outcome of study is death or BPD defined by NICHD criteria.
arm group label: Experimental
arm group type: Active Comparator
description: Curosurf + budesonide
arm group label: Placebo
arm group type: Placebo Comparator
description: Curosurf + saline
intervention type: Drug
intervention name: budesonide
description: Intra-tracheal instillation of a combination of budesonide/surfactant in preterm infants with RDS to prevent BPD
arm group label: Experimental
other name: pulmicort
intervention type: Drug
intervention name: Saline
description: Intra-tracheal instillation of a combination of saline/surfactant in preterm infants with RDS to prevent BPD
arm group label: Placebo
other name: sodium chloride
criteria: 
gender: All
minimum age: 30 Minutes
maximum age: 4 Hours
healthy volunteers: No
last name: Tsu F Yeh, M.D., Ph.D.
role: Principal Investigator
affiliation: Maternal Child Health Research Center, Taipei Medical University
facility: 
country: Taiwan
citation: Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.
PMID: 26351971
citation: Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, Pyati S, Tsai CH. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008 May;121(5):e1310-8. doi: 10.1542/peds.2007-1973. Epub 2008 Apr 21.
PMID: 18426851
citation: Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF. A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr. 2010 Apr;156(4):537-41. doi: 10.1016/j.jpeds.2009.10.049. Epub 2010 Feb 6.
PMID: 20138301
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Bronchopulmonary Dysplasia
mesh term: Budesonide
sharing ipd: No