<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/NCT03779776</url>
  </required_header>
  <id_info>
    <org_study_id>VAD-PRETERM</org_study_id>
    <nct_id>NCT03779776</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Early Vitamin AD Supplementation in Very Preterm Infants</brief_title>
  <official_title>The Department of Neonatology, Zhengzhou Children's Hospital</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhengzhou Children's Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhengzhou Children's Hospital, China</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bronchopulmonary dysplasia (BPD) is the most prevalent longterm morbidity among surviving&#xD;
      extremely preterm infants and has a multifactorial etiology. BPD is associated with later&#xD;
      risk of reactive airways disease, such as asthma, post neonatal mortality and adverse&#xD;
      neurodevelopmental outcomes.Retinopathy of prematurity (ROP) is a common retinal neovascular&#xD;
      disorder and a major cause of vision impairment or blindness in preterm infants, even with&#xD;
      aggressed current standard care.Accumulating epidemiologic evidence suggests that vitamin D&#xD;
      (VD) deficiency or insufficiency is associated with respiratory disease and metabolic bone&#xD;
      disease in premature children.Vitamin A (VA) plays an integral part in lung growth and&#xD;
      differentiation. VA is an essential micronutrient for normal visual function.&#xD;
&#xD;
      Our prospective double-blinded randomized controlled trial will include infants born at &lt;32&#xD;
      weeks' gestation and admitted to six tertiary NICUs in China. Infants in the intervention&#xD;
      (vitamin AD drops) group will receive the daily dose VA at 1500 IU/day with VD 500 IU/day,&#xD;
      added to their enteral feeds in drop form as soon as minimal feeding was introduced, and&#xD;
      continued to 28 days or discharge. Infants in the control group will receive an equivalent&#xD;
      volume of a placebo solution. Following informed consent, enrolled infants will be randomly&#xD;
      allocated to the control or VAD group. The primary outcome is bronchopulmonary dysplasia&#xD;
      (BPD) , ROP, or metabolic bone disease and the secondary outcomes are mortality; NEC ≥ stage&#xD;
      2; ; late-onset sepsis; weight gain, change in weight, increase in length, increase in head&#xD;
      circumference; time to full enteral feeds; and number and type of critical incident reports.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Actual">June 28, 2020</completion_date>
  <primary_completion_date type="Actual">June 28, 2020</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>rates of bronchopulmonary dysplasia</measure>
    <time_frame>1 year</time_frame>
    <description>The rates of bronchopulmonary dysplasia with early vitamin AD supplementation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>rates of retinopathy of prematurity</measure>
    <time_frame>1 year</time_frame>
    <description>The rates of retinopathy of prematurity with early vitamin AD supplementation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metaboloc bone disease</measure>
    <time_frame>1 year</time_frame>
    <description>The rates of Metaboloc bone disease of prematurity with early vitamin AD supplementation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>rates of Necrotizing enterocolitis</measure>
    <time_frame>1 year</time_frame>
    <description>The rates of Necrotizing enterocolitis with early vitamin AD supplementation</description>
  </secondary_outcome>
  <other_outcome>
    <measure>rates of late-onset sepsis</measure>
    <time_frame>1 year</time_frame>
    <description>The rates of late-onset sepsis with early vitamin AD supplementation</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">676</enrollment>
  <condition>Efficacy and Safety</condition>
  <arm_group>
    <arm_group_label>Vitamin AD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d, containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d,VD 80 IU/kg/d ) within daily on parenteral nutrition until fed 120ml/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vitamin AD</intervention_name>
    <description>In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at 1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.</description>
    <arm_group_label>Vitamin AD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age&lt;32 weeks,&#xD;
&#xD;
          -  &lt;96 hours of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  genetic metabolic diseases;&#xD;
&#xD;
          -  congenital major abnormalities;&#xD;
&#xD;
          -  congenital non-bacterial infection with overt signs at birth;&#xD;
&#xD;
          -  terminal stage of illness (pH &lt; 7.0 or hypoxia with bradycardia&gt;2 h);&#xD;
&#xD;
          -  ≥ grade III intracranial hemorrhage;&#xD;
&#xD;
          -  lacking parental consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Hour</minimum_age>
    <maximum_age>96 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shuying Luo, MD</last_name>
    <role>Study Director</role>
    <affiliation>Zhengzhou Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zhengzhou Children's Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450018</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 16, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>September 2, 2021</last_update_submitted>
  <last_update_submitted_qc>September 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Zhengzhou Children's Hospital, China</investigator_affiliation>
    <investigator_full_name>Huiqing Sun</investigator_full_name>
    <investigator_title>Vice Director of Neonatology department</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamins</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/NCT03779776
org study id: VAD-PRETERM
nct id: NCT03779776
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Bronchopulmonary dysplasia (BPD) is the most prevalent longterm morbidity among surviving
      extremely preterm infants and has a multifactorial etiology. BPD is associated with later
      risk of reactive airways disease, such as asthma, post neonatal mortality and adverse
      neurodevelopmental outcomes.Retinopathy of prematurity (ROP) is a common retinal neovascular
      disorder and a major cause of vision impairment or blindness in preterm infants, even with
      aggressed current standard care.Accumulating epidemiologic evidence suggests that vitamin D
      (VD) deficiency or insufficiency is associated with respiratory disease and metabolic bone
      disease in premature children.Vitamin A (VA) plays an integral part in lung growth and
      differentiation. VA is an essential micronutrient for normal visual function.

      Our prospective double-blinded randomized controlled trial will include infants born at <32
      weeks' gestation and admitted to six tertiary NICUs in China. Infants in the intervention
      (vitamin AD drops) group will receive the daily dose VA at 1500 IU/day with VD 500 IU/day,
      added to their enteral feeds in drop form as soon as minimal feeding was introduced, and
      continued to 28 days or discharge. Infants in the control group will receive an equivalent
      volume of a placebo solution. Following informed consent, enrolled infants will be randomly
      allocated to the control or VAD group. The primary outcome is bronchopulmonary dysplasia
      (BPD) , ROP, or metabolic bone disease and the secondary outcomes are mortality; NEC ≥ stage
      2; ; late-onset sepsis; weight gain, change in weight, increase in length, increase in head
      circumference; time to full enteral feeds; and number and type of critical incident reports.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: rates of bronchopulmonary dysplasia
time frame: 1 year
description: The rates of bronchopulmonary dysplasia with early vitamin AD supplementation
measure: rates of retinopathy of prematurity
time frame: 1 year
description: The rates of retinopathy of prematurity with early vitamin AD supplementation
measure: Metaboloc bone disease
time frame: 1 year
description: The rates of Metaboloc bone disease of prematurity with early vitamin AD supplementation
measure: rates of Necrotizing enterocolitis
time frame: 1 year
description: The rates of Necrotizing enterocolitis with early vitamin AD supplementation
measure: rates of late-onset sepsis
time frame: 1 year
description: The rates of late-onset sepsis with early vitamin AD supplementation
arm group label: Vitamin AD
arm group type: Experimental
description: In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d, containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.
arm group label: Control
arm group type: Placebo Comparator
description: In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d,VD 80 IU/kg/d ) within daily on parenteral nutrition until fed 120ml/kg.
intervention type: Other
intervention name: Vitamin AD
description: In Vitamin AD group, the very preterm infants will receive the daily vitamin AD with vitamin A at 1500 IU/day and vitamin D at 500 IU/day in drop form added to their enteral feeds when minimal feeding is introduced, and continue to 28 days or discharge. In this group ,the patient also will receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.
arm group label: Vitamin AD
intervention type: Other
intervention name: Control
description: In this group ,the patient will only receive standard intravenous multivitamin preparation (1 ml/kg/d,containing VA 230 IU/kg/d, VD 80 IU/kg/d) within daily on parenteral nutrition until fed 120ml/kg.
arm group label: Control
criteria: 
gender: All
minimum age: 1 Hour
maximum age: 96 Hours
healthy volunteers: No
last name: Shuying Luo, MD
role: Study Director
affiliation: Zhengzhou Children's Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Zhengzhou Children's Hospital, China
investigator full name: Huiqing Sun
investigator title: Vice Director of Neonatology department
mesh term: Vitamins
sharing ipd: No