<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/NCT03295162</url>
  </required_header>
  <id_info>
    <org_study_id>Pediatrics Dept-ASU</org_study_id>
    <nct_id>NCT03295162</nct_id>
  </id_info>
  <brief_title>Effects of Melatonin as a Novel Antioxidant and Free Radicals Scavenger in Neonatal Sepsis</brief_title>
  <official_title>Effects of Melatonin as a Novel Antioxidant and Free Radicals Scavenger in Neonatal Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mohamed Hussein Metwally</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams 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>
      Assess the efficacy of melatonin as an adjuvant in the treatment of free radical disease in&#xD;
      septic preterms receiving melatonin compared to those on conventional treatment through&#xD;
      measuring the level of Malondialdehyde as a marker of oxidative stress and by comparing other&#xD;
      clinical and laboratory parameters of sepsis in both groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized controlled trial. It will be provisionally conducted on 55 neonates&#xD;
      admitted to the neonatal intensive care units (NICUs) of Ain Shams University Hospitals,&#xD;
      Cairo, Egypt.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      The study will include:Preterm infants (less than 37 weeks gestational age). Evidence of&#xD;
      neonatal sepsis.&#xD;
&#xD;
      Exclusion Criteria: Neonate with evidence of any of the following will be excluded:&#xD;
&#xD;
      Infants with hypoxic ischemic encephalopathy. Infants on nothing per os. Infants with high&#xD;
      oxygen needs either on invasive or non-invasive mechanical ventilation.&#xD;
&#xD;
      Group Classification:&#xD;
&#xD;
      Studied neonates will be completely evaluated and subsequently discriminated, into 2 main&#xD;
      groups:Sepsis group: including neonates with proved sepsis. These will be subsequently&#xD;
      randomized by permuted block randomization according to sequence of enrollment into:Subgroup&#xD;
      A: neonates with odd numbers will receive melatonin.&#xD;
&#xD;
      Subgroup B: neonates with even numbers will not receive the medicine. Non Sepsis group:&#xD;
      healthy neonates, in whom sepsis will be ruled-out on the basis of absence of any clinical or&#xD;
      laboratory evidence suggestive of infection.&#xD;
&#xD;
      Diagnosis of neonatal sepsis will be established based on the presence of: risk factors of&#xD;
      sepsis (e.g., prematurity, chorioamnionitis), any clinical evidence suggestive of sepsis,&#xD;
      quantitative C-reactive protein (CRP) levels ≥6 mg/dL, Rodwell's hematological scores ≥3,&#xD;
      with or without positive blood culture results&#xD;
&#xD;
        1. Comprehensive history taking including:&#xD;
&#xD;
           A.Antenatal history: Maternal age, maternal diseases; Maternal diabetic control,&#xD;
           maternal fever, infection, prolonged rupture of membranes &gt;=18 hours, malodorous vaginal&#xD;
           discharge.&#xD;
&#xD;
           B.Natal history: Gestational age, sex, and mode of delivery. C.Postnatal history: APGAR&#xD;
           score, Respiratory distress and/or cyanosis.&#xD;
&#xD;
        2. Gestational age will be estimated using the date of the last menstrual period, early&#xD;
           antenatal ultrasound if present when available and confirmed by the new Ballard scoring&#xD;
           system&#xD;
&#xD;
        3. Full clinical examination including: chest, cardiac, abdominal and neurological&#xD;
           examination.&#xD;
&#xD;
        4. Clinical signs of infection: lethargy, irritability, prolonged capillary refill,&#xD;
           tachycardia, respiratory distress, apnea, convulsions, abdominal distension, feeding&#xD;
           intolerance, hyperglycemia, temperature instability and bleeding.&#xD;
&#xD;
        5. Assessment of the hemodynamic state of the neonates: mean arterial blood pressure&#xD;
           (MABP), urinary output, temperature, capillary refill time.&#xD;
&#xD;
        6. Laboratory investigations Complete blood picture (CBC) with differential leucocytic&#xD;
           count. C- reactive protein (CRP) quantitative assay. Blood cultures. MDA assay: blood&#xD;
           samples will be collected in plain tubes from peripheral veins or central venous access.&#xD;
           Samples will be allowed to clot before centrifugation for 15 minutes and serum will be&#xD;
           stored at (-20 degree C) until MDA analysis using MDA competitive ELISA-kit.&#xD;
&#xD;
           Blood samples will be collected from all included neonates at enrollment and in day one&#xD;
           for healthy group.&#xD;
&#xD;
           As for subgroup A, other samples will be withdrawn at 4 and 72 hours after melatonin&#xD;
           administration to assess serum level of malondialdehyde while for subgroup B another&#xD;
           sample will be withdrawn after 72 hours&#xD;
&#xD;
        7. Melatonin Medication:&#xD;
&#xD;
           Melatonin 10 mg rapid release capsules (puritans pride) will be used. Melatonin will be&#xD;
           given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in&#xD;
           two doses of 10 mg each(2 ml ), with a 1-hour interval.(Gitto et al., 2000)&#xD;
&#xD;
        8. Treatment protocol: All neonates will be managed according to the protocol of NICU&#xD;
           beside routine neonatal care.&#xD;
&#xD;
      Babies admitted to NICU will be bathed, placed in incubator, attached to monitor.&#xD;
&#xD;
      Cannula will be inserted, IV fluids is started and IV antibiotics. If there is respiratory&#xD;
      distress: O2 or ventilation is started, usually feeds are delayed to day 2 or day 3 (or even&#xD;
      later) according the severity of condition (clinical decision according to the attending&#xD;
      neonatologist).&#xD;
&#xD;
      If no distress and the baby is well: trophic feeds will be started (10ml/kg/day milk), feeds&#xD;
      are increased in 10-20ml/kg/day according to baby tolerance, and the condition of the baby&#xD;
      (clinical decision according to the attending neonatologist), IV fluids are reduced&#xD;
      gradually.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 26, 2015</start_date>
  <completion_date type="Actual">September 1, 2017</completion_date>
  <primary_completion_date type="Actual">March 1, 2017</primary_completion_date>
  <phase>Phase 1/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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Melatonin as an antioxidant and free radicals scavenger in Neonatal sepsis</measure>
    <time_frame>3 days</time_frame>
    <description>efficacy of melatonin as an adjuvant in the treatment of free radical disease in septic preterms receiving melatonin compared to those on conventional treatment through measuring the level of Malondialdehyde as a marker of oxidative stress</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>melatonin as an adjuvant in management of neonatal sepsis</measure>
    <time_frame>3 days</time_frame>
    <description>efficacy of melatonin as an adjuvant in the treatment of septic preterms compared to those on conventional treatment and by comparing other clinical and laboratory parameters of sepsis in both groups</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>Sepsis A Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>neonates diagnosed with Sepsis and will receive melatonin. 10 mg product as a total dose of 20 mg .together with conventional treatment of Neonatal sepsis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sepsis B Group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>neonates diagnosed with Sepsis and willnot receive melatonin., they will recieve only the conventional treatment of Neonatal Sepsis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>healthy neonates, in whom sepsis will be ruled-out on the basis of absence of any clinical or laboratory evidence suggestive of infection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin 10 mg</intervention_name>
    <description>Melatonin will be given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in two doses of 10 mg each(2 ml ), with a 1-hour interval. to one group together with conventional treatment</description>
    <arm_group_label>Sepsis A Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Conventional treatment of neonatal sepsis</intervention_name>
    <description>Conventional treatment of neonatal sepsis including antibiotics,IV fluids, Total Parenteral Nutrition,etc...</description>
    <arm_group_label>Sepsis A Group</arm_group_label>
    <arm_group_label>Sepsis B Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Preterm infants ( less than 37 weeks gestational age). Evidence of neonatal sepsis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Infants with hypoxic ischemic encephalopath Infants on nothing per os. Infants with high&#xD;
        oxygen needs either on invasive or non-invasive mechanical ventilation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>28 Days</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>September 25, 2017</last_update_submitted>
  <last_update_submitted_qc>September 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Mohamed Hussein Metwally</investigator_full_name>
    <investigator_title>Assistant Lecturer</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Neonatal Sepsis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03295162
org study id: Pediatrics Dept-ASU
nct id: NCT03295162
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Assess the efficacy of melatonin as an adjuvant in the treatment of free radical disease in
      septic preterms receiving melatonin compared to those on conventional treatment through
      measuring the level of Malondialdehyde as a marker of oxidative stress and by comparing other
      clinical and laboratory parameters of sepsis in both groups.
This is a randomized controlled trial. It will be provisionally conducted on 55 neonates
      admitted to the neonatal intensive care units (NICUs) of Ain Shams University Hospitals,
      Cairo, Egypt.

      Inclusion criteria:

      The study will include:Preterm infants (less than 37 weeks gestational age). Evidence of
      neonatal sepsis.

      Exclusion Criteria: Neonate with evidence of any of the following will be excluded:

      Infants with hypoxic ischemic encephalopathy. Infants on nothing per os. Infants with high
      oxygen needs either on invasive or non-invasive mechanical ventilation.

      Group Classification:

      Studied neonates will be completely evaluated and subsequently discriminated, into 2 main
      groups:Sepsis group: including neonates with proved sepsis. These will be subsequently
      randomized by permuted block randomization according to sequence of enrollment into:Subgroup
      A: neonates with odd numbers will receive melatonin.

      Subgroup B: neonates with even numbers will not receive the medicine. Non Sepsis group:
      healthy neonates, in whom sepsis will be ruled-out on the basis of absence of any clinical or
      laboratory evidence suggestive of infection.

      Diagnosis of neonatal sepsis will be established based on the presence of: risk factors of
      sepsis (e.g., prematurity, chorioamnionitis), any clinical evidence suggestive of sepsis,
      quantitative C-reactive protein (CRP) levels ≥6 mg/dL, Rodwell's hematological scores ≥3,
      with or without positive blood culture results

        1. Comprehensive history taking including:

           A.Antenatal history: Maternal age, maternal diseases; Maternal diabetic control,
           maternal fever, infection, prolonged rupture of membranes >=18 hours, malodorous vaginal
           discharge.

           B.Natal history: Gestational age, sex, and mode of delivery. C.Postnatal history: APGAR
           score, Respiratory distress and/or cyanosis.

        2. Gestational age will be estimated using the date of the last menstrual period, early
           antenatal ultrasound if present when available and confirmed by the new Ballard scoring
           system

        3. Full clinical examination including: chest, cardiac, abdominal and neurological
           examination.

        4. Clinical signs of infection: lethargy, irritability, prolonged capillary refill,
           tachycardia, respiratory distress, apnea, convulsions, abdominal distension, feeding
           intolerance, hyperglycemia, temperature instability and bleeding.

        5. Assessment of the hemodynamic state of the neonates: mean arterial blood pressure
           (MABP), urinary output, temperature, capillary refill time.

        6. Laboratory investigations Complete blood picture (CBC) with differential leucocytic
           count. C- reactive protein (CRP) quantitative assay. Blood cultures. MDA assay: blood
           samples will be collected in plain tubes from peripheral veins or central venous access.
           Samples will be allowed to clot before centrifugation for 15 minutes and serum will be
           stored at (-20 degree C) until MDA analysis using MDA competitive ELISA-kit.

           Blood samples will be collected from all included neonates at enrollment and in day one
           for healthy group.

           As for subgroup A, other samples will be withdrawn at 4 and 72 hours after melatonin
           administration to assess serum level of malondialdehyde while for subgroup B another
           sample will be withdrawn after 72 hours

        7. Melatonin Medication:

           Melatonin 10 mg rapid release capsules (puritans pride) will be used. Melatonin will be
           given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in
           two doses of 10 mg each(2 ml ), with a 1-hour interval.(Gitto et al., 2000)

        8. Treatment protocol: All neonates will be managed according to the protocol of NICU
           beside routine neonatal care.

      Babies admitted to NICU will be bathed, placed in incubator, attached to monitor.

      Cannula will be inserted, IV fluids is started and IV antibiotics. If there is respiratory
      distress: O2 or ventilation is started, usually feeds are delayed to day 2 or day 3 (or even
      later) according the severity of condition (clinical decision according to the attending
      neonatologist).

      If no distress and the baby is well: trophic feeds will be started (10ml/kg/day milk), feeds
      are increased in 10-20ml/kg/day according to baby tolerance, and the condition of the baby
      (clinical decision according to the attending neonatologist), IV fluids are reduced
      gradually.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Melatonin as an antioxidant and free radicals scavenger in Neonatal sepsis
time frame: 3 days
description: efficacy of melatonin as an adjuvant in the treatment of free radical disease in septic preterms receiving melatonin compared to those on conventional treatment through measuring the level of Malondialdehyde as a marker of oxidative stress
measure: melatonin as an adjuvant in management of neonatal sepsis
time frame: 3 days
description: efficacy of melatonin as an adjuvant in the treatment of septic preterms compared to those on conventional treatment and by comparing other clinical and laboratory parameters of sepsis in both groups
arm group label: Sepsis A Group
arm group type: Experimental
description: neonates diagnosed with Sepsis and will receive melatonin. 10 mg product as a total dose of 20 mg .together with conventional treatment of Neonatal sepsis
arm group label: Sepsis B Group
arm group type: Sham Comparator
description: neonates diagnosed with Sepsis and willnot receive melatonin., they will recieve only the conventional treatment of Neonatal Sepsis
arm group label: Control
arm group type: No Intervention
description: healthy neonates, in whom sepsis will be ruled-out on the basis of absence of any clinical or laboratory evidence suggestive of infection.
intervention type: Drug
intervention name: Melatonin 10 mg
description: Melatonin will be given at a total dose of 20 mg dissolved in 4 ml of distilled water via enteral route in two doses of 10 mg each(2 ml ), with a 1-hour interval. to one group together with conventional treatment
arm group label: Sepsis A Group
intervention type: Combination Product
intervention name: Conventional treatment of neonatal sepsis
description: Conventional treatment of neonatal sepsis including antibiotics,IV fluids, Total Parenteral Nutrition,etc...
arm group label: Sepsis A Group
arm group label: Sepsis B Group
criteria: 
gender: All
minimum age: 1 Day
maximum age: 28 Days
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor-Investigator
investigator affiliation: Ain Shams University
investigator full name: Mohamed Hussein Metwally
investigator title: Assistant Lecturer
mesh term: Sepsis
mesh term: Toxemia
mesh term: Neonatal Sepsis
mesh term: Melatonin
sharing ipd: Undecided