<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/NCT03274596</url>
  </required_header>
  <id_info>
    <org_study_id>212250-10231</org_study_id>
    <nct_id>NCT03274596</nct_id>
  </id_info>
  <brief_title>Effect of Vitamin E for Prevention of Retinopathy of Prematurity: A Randomized Clinical Trial.</brief_title>
  <official_title>Effect of Vitamin E Supplementation on Oxidative Stress and Retinopathy of Prematurity in Preterm Infants &lt;1500 g: A Randomized Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes</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 retinopathy of prematurity (ROP) is a public health problem, the main causes of ROP are&#xD;
      prematurity, use of oxygen, malnutrition and oxidative stress. Vitamin E was used beforehand&#xD;
      however its use was stopped because of its association with sepsis and enterocolitis caused&#xD;
      by the excipient of vitamin E. The purpose of this study is to use vitamin E to prevent ROP,&#xD;
      without the previously used excipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Antioxidant defence mechanisms include cellular and extracellular enzymes. Vitamin E is the&#xD;
      main fat-soluble vitamin responsible for the protection of cell membranes against&#xD;
      peroxidation, thus, it protects polyunsaturated fatty acids from peroxidation which is a step&#xD;
      in the pathogenesis of ROP.&#xD;
&#xD;
      Previous research on the roles of vitamin E, in the prevention of BPD and ROP was halted&#xD;
      because of complications involving sepsis and necrotising enterocolitis. These complications&#xD;
      were caused by the compositions of vitamin E oral presentations, which contain polyethylene&#xD;
      glycol, propylene glycol, ethanol and, polysorbate 80. These substances, which are used as&#xD;
      excipients, may generate adverse effects in premature newborns. These preparations were not&#xD;
      used in this project to avoid the development of necrotising enterocolitis, and because these&#xD;
      formulations are not commercially available in Mexico.&#xD;
&#xD;
      The infants were randomly assigned to one of two groups using a computerized random number&#xD;
      generator sequence; this process was handled by the hospital pharmacy staff. The treated&#xD;
      group, received vitamin E 12.5 IU orally every 12 hours, from 72 h after birth until 28 days&#xD;
      of age, the first blood sample collected from the newborns before the intervention was&#xD;
      considered the baseline, and subsequent samples were obtained at 15 and 28 days of age.&#xD;
&#xD;
      Control group: received orally sterile water (placebo)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2013</start_date>
  <completion_date type="Actual">December 1, 2015</completion_date>
  <primary_completion_date type="Actual">October 1, 2015</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>
    <intervention_model_description>participants were randomly assigned to one of two treatmenst (A and B) using a computarized random number generator sequence; this process was handled by the hospital pharmacy staff. Group A: received vitamin E 12.5 IU orally every 12 hours, from 72 h after birth until 28 days of age, Group B: received orally sterile water (placebo) orally every 12 hours, from 72 h after birth until 28 days of age,</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The placebo was made by a pharmacologist and was the only person who knows the treatment of A and B. The placebo was administered by nursing staff and had the same appearance and amount as vitamin E. Neither the parents of the participants nor the researchers involved in the care or analysis of the data knew the content of the treatment and B until the end of the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of retinopathy of prematurity</measure>
    <time_frame>For the first retinopathy diagnosis, ophthalmological evaluation was performed at 28 days of birth.</time_frame>
    <description>Retinopathy of prematurity was classified according to the International Classification of Retinopathy of Prematurity revisited 2005.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of bronchopulmonary dysplasia (BPD)</measure>
    <time_frame>Incidence of BPD was measured in each participant at 28 days old.</time_frame>
    <description>BPD diagnosis was established according to the National Institute of Child Health and Human Development (NICHD) Workshop summary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of bronchopulmonary dysplasia (BPD)</measure>
    <time_frame>Severity of BPD was measured at corrected 36 weeks' gestational age.</time_frame>
    <description>Severity was classified into one of three stages: mild, when the patient did not required oxygen; moderate, when the patient required 30% oxygen; and severe when the patient required &gt;30% oxygen, had nasal continuous positive airway pressure (CPAP), or mechanical ventilation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Retinopathy of Prematurity</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A: received 12.5 IU of vitamin E orally every 12 hours, from 72 h of birth to 28 days old.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group B: received 12.5 IU of placebo orally every 12 hours, from 72 hours of birth to 28 days old.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin E</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newborn weight &lt; 1500 g&#xD;
&#xD;
          -  Diagnosed respiratory distress syndrome (RDS)&#xD;
&#xD;
          -  Patients who required mechanical ventilation or CPAP&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Congenital malformations&#xD;
&#xD;
          -  Rh incompatibility&#xD;
&#xD;
          -  Non-immune or immune hydrops fetalis&#xD;
&#xD;
          -  Intraventricular haemorrhage III/IV grade&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Days</minimum_age>
    <maximum_age>3 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Silvia Romero-Maldonado, M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Nacional de Perinatología Isidro Espinosa de los Reyes</affiliation>
  </overall_official>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>September 5, 2017</last_update_submitted>
  <last_update_submitted_qc>September 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes</investigator_affiliation>
    <investigator_full_name>Silvia Romero-Maldonado</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Oxidative Damage</keyword>
  <keyword>Vitamin E</keyword>
  <keyword>Total Antioxidant Capacity</keyword>
  <keyword>Retinopathy of Prematurity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Retinopathy of Prematurity</mesh_term>
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin E</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/NCT03274596
org study id: 212250-10231
nct id: NCT03274596
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The retinopathy of prematurity (ROP) is a public health problem, the main causes of ROP are
      prematurity, use of oxygen, malnutrition and oxidative stress. Vitamin E was used beforehand
      however its use was stopped because of its association with sepsis and enterocolitis caused
      by the excipient of vitamin E. The purpose of this study is to use vitamin E to prevent ROP,
      without the previously used excipients.
Antioxidant defence mechanisms include cellular and extracellular enzymes. Vitamin E is the
      main fat-soluble vitamin responsible for the protection of cell membranes against
      peroxidation, thus, it protects polyunsaturated fatty acids from peroxidation which is a step
      in the pathogenesis of ROP.

      Previous research on the roles of vitamin E, in the prevention of BPD and ROP was halted
      because of complications involving sepsis and necrotising enterocolitis. These complications
      were caused by the compositions of vitamin E oral presentations, which contain polyethylene
      glycol, propylene glycol, ethanol and, polysorbate 80. These substances, which are used as
      excipients, may generate adverse effects in premature newborns. These preparations were not
      used in this project to avoid the development of necrotising enterocolitis, and because these
      formulations are not commercially available in Mexico.

      The infants were randomly assigned to one of two groups using a computerized random number
      generator sequence; this process was handled by the hospital pharmacy staff. The treated
      group, received vitamin E 12.5 IU orally every 12 hours, from 72 h after birth until 28 days
      of age, the first blood sample collected from the newborns before the intervention was
      considered the baseline, and subsequent samples were obtained at 15 and 28 days of age.

      Control group: received orally sterile water (placebo)
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: participants were randomly assigned to one of two treatmenst (A and B) using a computarized random number generator sequence; this process was handled by the hospital pharmacy staff. Group A: received vitamin E 12.5 IU orally every 12 hours, from 72 h after birth until 28 days of age, Group B: received orally sterile water (placebo) orally every 12 hours, from 72 h after birth until 28 days of age,
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The placebo was made by a pharmacologist and was the only person who knows the treatment of A and B. The placebo was administered by nursing staff and had the same appearance and amount as vitamin E. Neither the parents of the participants nor the researchers involved in the care or analysis of the data knew the content of the treatment and B until the end of the study.
measure: Incidence of retinopathy of prematurity
time frame: For the first retinopathy diagnosis, ophthalmological evaluation was performed at 28 days of birth.
description: Retinopathy of prematurity was classified according to the International Classification of Retinopathy of Prematurity revisited 2005.
measure: Incidence of bronchopulmonary dysplasia (BPD)
time frame: Incidence of BPD was measured in each participant at 28 days old.
description: BPD diagnosis was established according to the National Institute of Child Health and Human Development (NICHD) Workshop summary.
measure: Severity of bronchopulmonary dysplasia (BPD)
time frame: Severity of BPD was measured at corrected 36 weeks' gestational age.
description: Severity was classified into one of three stages: mild, when the patient did not required oxygen; moderate, when the patient required 30% oxygen; and severe when the patient required >30% oxygen, had nasal continuous positive airway pressure (CPAP), or mechanical ventilation.
arm group label: Treatment A
arm group type: Active Comparator
description: Group A: received 12.5 IU of vitamin E orally every 12 hours, from 72 h of birth to 28 days old.
arm group label: Treatment B
arm group type: Placebo Comparator
description: Group B: received 12.5 IU of placebo orally every 12 hours, from 72 hours of birth to 28 days old.
intervention type: Drug
intervention name: Vitamin E
arm group label: Treatment A
intervention type: Drug
intervention name: Placebo
arm group label: Treatment B
criteria: 
gender: All
minimum age: 3 Days
maximum age: 3 Days
healthy volunteers: No
last name: Silvia Romero-Maldonado, M.Sc.
role: Principal Investigator
affiliation: Instituto Nacional de Perinatología Isidro Espinosa de los Reyes
responsible party type: Principal Investigator
investigator affiliation: Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes
investigator full name: Silvia Romero-Maldonado
investigator title: Principal Investigator
mesh term: Retinal Diseases
mesh term: Retinopathy of Prematurity
mesh term: Premature Birth
mesh term: Vitamin E