<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/NCT01723683</url>
  </required_header>
  <id_info>
    <org_study_id>DMR101-IRB2-221</org_study_id>
    <nct_id>NCT01723683</nct_id>
  </id_info>
  <brief_title>Minimally Invasive Surfactant Therapy Followed by CPAP (MISTCPAP) in Preterm Infants With RDS</brief_title>
  <acronym>MISTCPAP</acronym>
  <official_title>Minimally Invasive Surfactant Therapy Followed by Early CPAP (MISTCPAP) in Very Preterm Infants With RDS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>China Medical University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is a reducing incidence of pneumothorax, PIE and the combined outcome of death or BPD&#xD;
      since the development of Surfactant therapy. A policy of intubation with surfactant&#xD;
      administration and mechanical ventilation has become a standard therapy of infants at high&#xD;
      risk of RDS. However, initial stabilization with CPAP and, if necessary, given rescue&#xD;
      surfactant therapy has remained the standard therapy for preterm infants. Evidence reveals&#xD;
      similar results with regard to mortality and neonatal morbidity between the above two&#xD;
      strategies. The investigators intend to develop a method of minimally invasive surfactant&#xD;
      therapy followed by early CPAP (MISTCPAP) in preterm Infants with high risk of RDS for&#xD;
      improving the outcomes and reducing the incidence of BPD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background. Reducing incidence of pneumothorax, PIE and the combined outcome of death or BPD&#xD;
      has been achieved since the development of Surfactant therapy. It is also approved that&#xD;
      initial stabilization with CPAP and rescue surfactant administration, if necessary, resulted&#xD;
      in less ventilator days and a trend towards lower risk of CLD. However, the number of infants&#xD;
      who are started on CPAP but ultimately require intubation for the administration of&#xD;
      surfactant within the first 72 hours remains high in the very preterm infants. Usually CPAP&#xD;
      failure is due to unremitting RDS requiring surfactant therapy. Outcomes in the infants with&#xD;
      CPAP as a whole could be improved further if the subgroup of infants showing early signs of&#xD;
      surfactant deficiency was to receive an early dose of surfactant.&#xD;
&#xD;
      Objective. This study intents to develop a method of minimally invasive surfactant therapy&#xD;
      followed by early CPAP (MISTCPAP) in preterm Infants with high risk of RDS for improving the&#xD;
      outcomes and reducing the incidence of BPD. We propose a prospective randomized controlled&#xD;
      trial to compare the MISTCPAP technique with the INSURE technique of surfactant&#xD;
      administration, which involves intubation solely for the purpose of surfactant administration&#xD;
      followed by immediate extubation to CPAP. The outcome of this trial could declare the effect&#xD;
      of the intubation and positive pressure ventilation on the effectiveness of surfactant&#xD;
      therapy.&#xD;
&#xD;
      Methods. This study will be approved by the Institutional Review Board (IRB) of CMUH.Very&#xD;
      preterm infants (GA &lt; 32 wks) admitted to NICU at CMUH from 1 February 2012 to 31 January&#xD;
      2013 are enrolled for the study. Infants who stayed in the hospital for less than 10 days or&#xD;
      those admitted after 24 hours of birth or with major congenital malformations will be&#xD;
      excluded. Eligible infants will be randomized to allocate to the 2 groups after birth using&#xD;
      simple randomization with sealed nontransparent envelopes after parental consent has been&#xD;
      obtained. MISTCPAP group: The 16Gz 13 cm length Angio-Cath is used and marked at a point&#xD;
      comparable to the level of infant's lip (weight in Kg + 6 cm as the routine ETT intubation)&#xD;
      to give the operator mark to secure the Angio-Cath during the procedure and prevent it from&#xD;
      going too far in or out of the trachea. The infant will be kept supine with upper part of&#xD;
      body raised about 30 degree, an oro-gastric (OG) tube should be inserted,and the infant&#xD;
      should not receive sedation. The CPAP may be removed transiently and the oxygen cannula or O2&#xD;
      flow over face may be given as indicated by saturation monitoring during the procedure. After&#xD;
      inserting the Angio-Cath, the laryngoscope should be removed after stabilizing the Catheter&#xD;
      with 2 fingers. Surfactant (Survanta©, Abbott, USA) 100 mg/kgBW, equivalent to 4 ml/kgBW per&#xD;
      dose will be drawn to a 10 ml syringe and should be instillated via the Angio-Cath. Prior to&#xD;
      the beginning of the clinical trial, every neonatal fellows should be trained to familiar the&#xD;
      procedure under the supervision of the PI (BH Su), and the average duration of procedure has&#xD;
      been achieved in the range of 1-3 minutes. All the vital signs, including Heart Rate,&#xD;
      Respiratory Rate,Oxygen Saturation (SpO2) and FiO2 (Fraction of Inspired Oxygen) requirements&#xD;
      should be monitored. After the procedure of surfactant instillation, the Angio-Cath should be&#xD;
      removed and the nCPAP should be resumed with CPAP level keep constant at 5 cmH2O. The&#xD;
      oro-gastric (OG) tube should be draw to check if any surfactant was instillated or reflexed&#xD;
      back to the stomach. As to the INSURE group, the procedure should be according to the&#xD;
      conventional surfactant treatment which involves intubation, surfactant(Survanta©, Abbott,&#xD;
      USA) 100 mg/kgBW, equivalent to 4 ml/kgBW divided to 4 liquors to inject into 4 positions&#xD;
      followed by amubagging and then extubation to CPAP. The clinical course in NICU of all&#xD;
      studied infants, including intraventricular hemorrhage (IVH), retinopathy of prematurity&#xD;
      (ROP), duration of ventilation, duration of hospital stay, infection, duration of oxygen&#xD;
      requirement and BPD should be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>February 2012</start_date>
  <completion_date type="Anticipated">January 2013</completion_date>
  <primary_completion_date type="Anticipated">January 2013</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Requirement of rescue intubation and mechanical ventilation</measure>
    <time_frame>72 hours</time_frame>
    <description>Failure of MISTCPAP procedure:&#xD;
SA1. Need for invasive ventilation, requiring either FiO2&gt; 0.6 or pCO2&gt; 65 mm Hg and pH &lt; 7.20 or both for more than 2 hours after surfactant administration up to 72 hrs of life 2. Intubation/requirement for mechanical ventilation within 48h after first intervention (same criteria as above:requiring either FiO2&gt; 0.6 or pCO2&gt; 65 mm Hg and pH &lt; 7.20 or both for more than 2 hours) 3. Acute deterioration during immediate intervention leading to intubation (e.g. severe bradycardia/resuscitation, pneumothorax)&#xD;
Failure for INSURE procedure:&#xD;
1. Failed extubation within 15 min after intubation for surfactant application</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>1.Incidence of grade 3 /4 IVH (intraventricular hemorrhage),PVL (periventricular leucomalacia),ROP (retinopathy of prematurity) requiring treatment,NEC (necrotizing enterocolitis)stage 2 and 3</measure>
    <time_frame>8 weeks of life</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2.Total duration of invasive and non-invasive ventilation (the extubation and weaning will follow the NICU guidelines), duration of oxygen supplementation until discharge</measure>
    <time_frame>participants will be followed for the duration of hospital stay, an expected average of 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3.Proportion of patients requiring oxygen supplementation at discharge 3.Proportion of patients requiring oxygen supplementation at discharge</measure>
    <time_frame>participants will be followed for the duration of hospital stay, an expected average of 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>4.Proportion of surfactant related adverse events like tube blockade, episodes of desaturation, bradycardia, pulmonary hemorrhage, pneumothorax differ in the two groups</measure>
    <time_frame>1 wk of life</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5.Total number of surfactant doses required compared in the two groups</measure>
    <time_frame>1 week of life</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6.Incidence of CLD. CLD is assessed at 36 corrected weeks as NICHD definition and severity</measure>
    <time_frame>at 36 corrected weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>7.Death Comparison of outcomes beteween the 2 groups will use OR and 95% CIs.</measure>
    <time_frame>8 weeks of life</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>MISTCPAP group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MISTCPAP group: Surfactant will be instillated via the Angio-Cath without endotracheal intubation and followed by CPAP.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>INSURE group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>INSURE group: The procedure of surfactant treatment should be according to the conventional surfactant treatment which involves intubation, surfactant divided to 4 liquors to inject into 4 positions followed by amubagging and then extubation to CPAP.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Surfactant</intervention_name>
    <arm_group_label>INSURE group</arm_group_label>
    <arm_group_label>MISTCPAP group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Very preterm infants (GA &lt; 32 wks) admitted to NICU at CMUH from 1 February 2012 to 31&#xD;
             January 2013 are enrolled for the study&#xD;
&#xD;
          2. Less than 36 hours of age&#xD;
&#xD;
          3. Clinical signs of RDS with requirement of FiO2 ≥ 0.35&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous Intubation or in imminent need of IMV because of e.g. apnea, severe&#xD;
             bradycardia or other deterioration not attributed to RDS, e.g. shock&#xD;
&#xD;
          2. Major congenital malformations&#xD;
&#xD;
          3. No parental consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Hour</minimum_age>
    <maximum_age>36 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bai-Horng Su, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Dept. of Pediatrics, China Medical University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hsieh-Yu Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>China Medical University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bai-Horng Su, MD, PhD</last_name>
    <phone>886-4-22052121</phone>
    <phone_ext>2061</phone_ext>
    <email>subh1168@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hsieh-Yu Lin, MD</last_name>
    <phone>886-4-22052121</phone>
    <phone_ext>2061</phone_ext>
    <email>hsyulin@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>China Medical University Children's Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bai-Horng Su, MD, PhD</last_name>
      <phone>886-4-22052121</phone>
      <phone_ext>2061</phone_ext>
      <email>subh1168@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>November 6, 2012</last_update_submitted>
  <last_update_submitted_qc>November 6, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 8, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Preterm infants</keyword>
  <keyword>RDS</keyword>
  <keyword>Surfactant</keyword>
  <keyword>MISTCPAP</keyword>
  <keyword>CPAP</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Surfactants</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01723683
org study id: DMR101-IRB2-221
nct id: NCT01723683
lead sponsor: 
has dmc: Yes
There is a reducing incidence of pneumothorax, PIE and the combined outcome of death or BPD
      since the development of Surfactant therapy. A policy of intubation with surfactant
      administration and mechanical ventilation has become a standard therapy of infants at high
      risk of RDS. However, initial stabilization with CPAP and, if necessary, given rescue
      surfactant therapy has remained the standard therapy for preterm infants. Evidence reveals
      similar results with regard to mortality and neonatal morbidity between the above two
      strategies. The investigators intend to develop a method of minimally invasive surfactant
      therapy followed by early CPAP (MISTCPAP) in preterm Infants with high risk of RDS for
      improving the outcomes and reducing the incidence of BPD.
Background. Reducing incidence of pneumothorax, PIE and the combined outcome of death or BPD
      has been achieved since the development of Surfactant therapy. It is also approved that
      initial stabilization with CPAP and rescue surfactant administration, if necessary, resulted
      in less ventilator days and a trend towards lower risk of CLD. However, the number of infants
      who are started on CPAP but ultimately require intubation for the administration of
      surfactant within the first 72 hours remains high in the very preterm infants. Usually CPAP
      failure is due to unremitting RDS requiring surfactant therapy. Outcomes in the infants with
      CPAP as a whole could be improved further if the subgroup of infants showing early signs of
      surfactant deficiency was to receive an early dose of surfactant.

      Objective. This study intents to develop a method of minimally invasive surfactant therapy
      followed by early CPAP (MISTCPAP) in preterm Infants with high risk of RDS for improving the
      outcomes and reducing the incidence of BPD. We propose a prospective randomized controlled
      trial to compare the MISTCPAP technique with the INSURE technique of surfactant
      administration, which involves intubation solely for the purpose of surfactant administration
      followed by immediate extubation to CPAP. The outcome of this trial could declare the effect
      of the intubation and positive pressure ventilation on the effectiveness of surfactant
      therapy.

      Methods. This study will be approved by the Institutional Review Board (IRB) of CMUH.Very
      preterm infants (GA < 32 wks) admitted to NICU at CMUH from 1 February 2012 to 31 January
      2013 are enrolled for the study. Infants who stayed in the hospital for less than 10 days or
      those admitted after 24 hours of birth or with major congenital malformations will be
      excluded. Eligible infants will be randomized to allocate to the 2 groups after birth using
      simple randomization with sealed nontransparent envelopes after parental consent has been
      obtained. MISTCPAP group: The 16Gz 13 cm length Angio-Cath is used and marked at a point
      comparable to the level of infant's lip (weight in Kg + 6 cm as the routine ETT intubation)
      to give the operator mark to secure the Angio-Cath during the procedure and prevent it from
      going too far in or out of the trachea. The infant will be kept supine with upper part of
      body raised about 30 degree, an oro-gastric (OG) tube should be inserted,and the infant
      should not receive sedation. The CPAP may be removed transiently and the oxygen cannula or O2
      flow over face may be given as indicated by saturation monitoring during the procedure. After
      inserting the Angio-Cath, the laryngoscope should be removed after stabilizing the Catheter
      with 2 fingers. Surfactant (Survanta©, Abbott, USA) 100 mg/kgBW, equivalent to 4 ml/kgBW per
      dose will be drawn to a 10 ml syringe and should be instillated via the Angio-Cath. Prior to
      the beginning of the clinical trial, every neonatal fellows should be trained to familiar the
      procedure under the supervision of the PI (BH Su), and the average duration of procedure has
      been achieved in the range of 1-3 minutes. All the vital signs, including Heart Rate,
      Respiratory Rate,Oxygen Saturation (SpO2) and FiO2 (Fraction of Inspired Oxygen) requirements
      should be monitored. After the procedure of surfactant instillation, the Angio-Cath should be
      removed and the nCPAP should be resumed with CPAP level keep constant at 5 cmH2O. The
      oro-gastric (OG) tube should be draw to check if any surfactant was instillated or reflexed
      back to the stomach. As to the INSURE group, the procedure should be according to the
      conventional surfactant treatment which involves intubation, surfactant(Survanta©, Abbott,
      USA) 100 mg/kgBW, equivalent to 4 ml/kgBW divided to 4 liquors to inject into 4 positions
      followed by amubagging and then extubation to CPAP. The clinical course in NICU of all
      studied infants, including intraventricular hemorrhage (IVH), retinopathy of prematurity
      (ROP), duration of ventilation, duration of hospital stay, infection, duration of oxygen
      requirement and BPD should be recorded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Requirement of rescue intubation and mechanical ventilation
time frame: 72 hours
description: Failure of MISTCPAP procedure:
SA1. Need for invasive ventilation, requiring either FiO2> 0.6 or pCO2> 65 mm Hg and pH < 7.20 or both for more than 2 hours after surfactant administration up to 72 hrs of life 2. Intubation/requirement for mechanical ventilation within 48h after first intervention (same criteria as above:requiring either FiO2> 0.6 or pCO2> 65 mm Hg and pH < 7.20 or both for more than 2 hours) 3. Acute deterioration during immediate intervention leading to intubation (e.g. severe bradycardia/resuscitation, pneumothorax)
Failure for INSURE procedure:
1. Failed extubation within 15 min after intubation for surfactant application
measure: 1.Incidence of grade 3 /4 IVH (intraventricular hemorrhage),PVL (periventricular leucomalacia),ROP (retinopathy of prematurity) requiring treatment,NEC (necrotizing enterocolitis)stage 2 and 3
time frame: 8 weeks of life
measure: 2.Total duration of invasive and non-invasive ventilation (the extubation and weaning will follow the NICU guidelines), duration of oxygen supplementation until discharge
time frame: participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: 3.Proportion of patients requiring oxygen supplementation at discharge 3.Proportion of patients requiring oxygen supplementation at discharge
time frame: participants will be followed for the duration of hospital stay, an expected average of 8 weeks
measure: 4.Proportion of surfactant related adverse events like tube blockade, episodes of desaturation, bradycardia, pulmonary hemorrhage, pneumothorax differ in the two groups
time frame: 1 wk of life
measure: 5.Total number of surfactant doses required compared in the two groups
time frame: 1 week of life
measure: 6.Incidence of CLD. CLD is assessed at 36 corrected weeks as NICHD definition and severity
time frame: at 36 corrected weeks
measure: 7.Death Comparison of outcomes beteween the 2 groups will use OR and 95% CIs.
time frame: 8 weeks of life
arm group label: MISTCPAP group
arm group type: Experimental
description: MISTCPAP group: Surfactant will be instillated via the Angio-Cath without endotracheal intubation and followed by CPAP.
arm group label: INSURE group
arm group type: Active Comparator
description: INSURE group: The procedure of surfactant treatment should be according to the conventional surfactant treatment which involves intubation, surfactant divided to 4 liquors to inject into 4 positions followed by amubagging and then extubation to CPAP.
intervention type: Drug
intervention name: Surfactant
arm group label: INSURE group
arm group label: MISTCPAP group
criteria: 
gender: All
minimum age: 1 Hour
maximum age: 36 Hours
healthy volunteers: No
last name: Bai-Horng Su, MD, PhD
role: Study Chair
affiliation: Dept. of Pediatrics, China Medical University Hospital
last name: Hsieh-Yu Lin, MD
role: Principal Investigator
affiliation: China Medical University Hospital
last name: Bai-Horng Su, MD, PhD
phone: 886-4-22052121
phone ext: 2061
email: subh1168@gmail.com
last name: Hsieh-Yu Lin, MD
phone: 886-4-22052121
phone ext: 2061
email: hsyulin@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Pulmonary Surfactants