<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/NCT04474327</url>
  </required_header>
  <id_info>
    <org_study_id>Montelukast in neonatal sepsis</org_study_id>
    <nct_id>NCT04474327</nct_id>
  </id_info>
  <brief_title>Role of Montelukast in Modulation of Response to Sepsis in Preterm Infants</brief_title>
  <official_title>Role of Montelukast in Modulation of Response to Sepsis in Preterm Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University Children Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mansoura University Children Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will conduct this study to explore the role of Montelukast in treatment of&#xD;
      neonatal sepsis and whether it has an effect on inflammatory markers, the duration of&#xD;
      antibiotic use, or on the patients´ outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Since inflammatory mediators play a crucial role in the pathophysiology of sepsis so&#xD;
      anti-inflammatory treatment, Montelukast, could be a beneficial therapy. The investigators&#xD;
      will conduct this pilot, open-labeled, randomized controlled intervention trial on 40&#xD;
      newborns admitted to NICU. The study will include late preterm infants with gestational age&#xD;
      (34 weeks to less than 37 weeks) with clinical evidence of sepsis. The study included an&#xD;
      intervention group (n=20) that will receive oral Montelukast for 10 days with antibiotics in&#xD;
      addition to the conventional antibiotic therapy regimen according to NICU policy while the&#xD;
      control group (n=20) will receive antibiotics in addition to the conventional antibiotic&#xD;
      therapy regimen according to NICU policy. After obtaining a fully informed written consent&#xD;
      from the neonate's parents or guardians, patients will be recruited and group allocated in&#xD;
      the study by random pick up of closed opaque sealed envelopes. Patients will be observed&#xD;
      clinically and by laboratory investigations along the duration of hospital admission through&#xD;
      a structured collection sheet. Demographic data, cause of admission, clinical data (vital&#xD;
      signs, activity, feeding intolerance, respiratory symptoms, duration of oxygen support, use&#xD;
      of inotropes) will be recorded. Blood sampling will be performed twice in both groups, on&#xD;
      admission, and 10 days after treatment. The following investigations will be carried out:&#xD;
      complete blood picture, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF alpha),&#xD;
      blood culture, Serum creatinine, Liver enzymes, and INR. A lumbar puncture will be performed&#xD;
      when the treating physicians suspect meningitis. Patients in both groups will be observed&#xD;
      along the duration of hospital admission to detect the outcome.&#xD;
&#xD;
      Patients in the intervention group, receiving Montelukast sodium (Singulair), will be given&#xD;
      at a dose according to body weight (1.5 kg to 2 kg, will be given 1.5 mg; greater than 2 kg,&#xD;
      will be given 2 mg). This dose was previously prescribed and given to preterm neonates&#xD;
      suffered from bronchopulmonary dysplasia by Kim et al. (2015). Four mg of the drug will be&#xD;
      dissolved in four ml milk and 1.5 - 2 ml milk only will be given once daily at 9 pm via an&#xD;
      orogastric tube or by oral administration for 10 days. Along the period of NICU admission,&#xD;
      patients receiving Montelukast will be closely observed for the development of any of its&#xD;
      side effects that including &quot;diarrhea, colic, vomiting, fever or cough&quot; (Adelsberg et al.,&#xD;
      2005).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 24, 2020</start_date>
  <completion_date type="Actual">February 10, 2021</completion_date>
  <primary_completion_date type="Actual">February 10, 2021</primary_completion_date>
  <phase>Phase 1</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>Change in serum tumor necrosis factor (TNF) Alpha level</measure>
    <time_frame>Measured twice: on admission and 10 days after receiving therapy</time_frame>
    <description>Change in serum level of TNF alpha is assessed by the difference between the admission level and its level at 10 days after receiving the therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The duration of NICU admission</measure>
    <time_frame>Counting the total duration of NICU admission</time_frame>
    <description>the total duration of NICU admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum C-reactive protein (CRP) level</measure>
    <time_frame>Measured twice: on admission and 10 days after receiving therapy</time_frame>
    <description>Serum C-reactive protein (CRP) level will be measured on admission and compare its level with the level at 10 days after receiving therapy. It will be measured in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients improvement, deterioration (Clinically and laboratory) or death</measure>
    <time_frame>determined at 10 days after receiving therapy</time_frame>
    <description>Patients are considered 1.improved when manifested clinically by no respiratory distress, normal temperature, no oxygen support, no inotropes, alert, not lethargic, tolerate feeding, increasing in body weight and laboratory by normal CBC , normal CRP, Culture negative. 2. Partially improved if patient still on intravenous fluid therapy, still on oxygen support, still on inotropes, CRP decreasing but still positive, and CBC still abnormal. 3. Deteriorated if developed complication as coagulopathy, septic shock or MODS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>use of positive pressure ventilation and its duration</measure>
    <time_frame>determined at 10 days after receiving therapy</time_frame>
    <description>use of positive pressure ventilation (receiving mechanical ventilation or CPAP) and the duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of use of inotropes</measure>
    <time_frame>determined at 10 days after receiving therapy</time_frame>
    <description>duration of inotropes (dopamine, epinephrine, norepinephrine)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Neonatal Sepsis</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention group will receive Montelukast Sodium for 10 days in addition to the conventional antibiotic therapy regimen and other supportive measures according to the policy of neonatal units and patients' needs. Montelukast sodium will be given at a dose according to body weight (1.5 kg to 2 kg, will be given 1.5 mg; greater than 2 kg, 2 mg will be given) this dose was calculated according to ( Kim et al. (2015). Four mg of the drug will be dissolved in four ml milk and 1.5 - 2 ml milk only will be given once daily at 9 pm via an orogastric tube or by oral administration for 10 days and patients of this group will be closely observed for development of Montelukast side effects as &quot;diarrhea, colic, vomiting, fever and cough&quot; (Adelsberg et al. 2005).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group will receive antibiotics and other supportive measures according to the policy of neonatal units and patients' needs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Montelukast Sodium</intervention_name>
    <description>Montelukast sodium (Singulair) will be given at a dose according to body weight. Four mg of the drug will be dissolved in four ml milk and the dose will be given once daily at 9 pm for 10 days.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Singulair</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Infants with gestational age from 34 weeks to less than 37 weeks (late preterm) and&#xD;
             weighted more than 1.5 Kg with clinical evidence of neonatal sepsis (Wynn 2016).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - 1. Infants presented initially with septic shock, multi-organ dysfunction syndrome&#xD;
        (MODS), disseminated intravascular coagulopathy.&#xD;
&#xD;
        2. Infants with major congenital malformations 3. Infants with chromosomal aberrations 4.&#xD;
        Postoperative patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>30 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hanan A El-Halaby</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mansoura University Children Hospital, Gomhuria street, 35116 Mansoura, Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mansoura University Childran Hospital</name>
      <address>
        <city>Mansoura</city>
        <state>Dakahlia</state>
        <zip>35116</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>van Adelsberg J, Moy J, Wei LX, Tozzi CA, Knorr B, Reiss TF. Safety, tolerability, and exploratory efficacy of montelukast in 6- to 24-month-old patients with asthma. Curr Med Res Opin. 2005 Jun;21(6):971-9. doi: 10.1185/030079905X48456.</citation>
    <PMID>15969897</PMID>
  </reference>
  <results_reference>
    <citation>Kim SB, Lee JH, Lee J, Shin SH, Eun HS, Lee SM, Sohn JA, Kim HS, Choi BM, Park MS, Park KI, Namgung R, Park MS. The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia. Korean J Pediatr. 2015 Sep;58(9):347-53. doi: 10.3345/kjp.2015.58.9.347. Epub 2015 Sep 21.</citation>
    <PMID>26512261</PMID>
  </results_reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>February 10, 2021</last_update_submitted>
  <last_update_submitted_qc>February 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University Children Hospital</investigator_affiliation>
    <investigator_full_name>Hanan El-Halaby</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Montelukast</keyword>
  <keyword>TNF alpha</keyword>
  <keyword>premature infant</keyword>
  <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>Montelukast</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/NCT04474327
org study id: Montelukast in neonatal sepsis
nct id: NCT04474327
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The investigators will conduct this study to explore the role of Montelukast in treatment of
      neonatal sepsis and whether it has an effect on inflammatory markers, the duration of
      antibiotic use, or on the patients´ outcome.
Since inflammatory mediators play a crucial role in the pathophysiology of sepsis so
      anti-inflammatory treatment, Montelukast, could be a beneficial therapy. The investigators
      will conduct this pilot, open-labeled, randomized controlled intervention trial on 40
      newborns admitted to NICU. The study will include late preterm infants with gestational age
      (34 weeks to less than 37 weeks) with clinical evidence of sepsis. The study included an
      intervention group (n=20) that will receive oral Montelukast for 10 days with antibiotics in
      addition to the conventional antibiotic therapy regimen according to NICU policy while the
      control group (n=20) will receive antibiotics in addition to the conventional antibiotic
      therapy regimen according to NICU policy. After obtaining a fully informed written consent
      from the neonate's parents or guardians, patients will be recruited and group allocated in
      the study by random pick up of closed opaque sealed envelopes. Patients will be observed
      clinically and by laboratory investigations along the duration of hospital admission through
      a structured collection sheet. Demographic data, cause of admission, clinical data (vital
      signs, activity, feeding intolerance, respiratory symptoms, duration of oxygen support, use
      of inotropes) will be recorded. Blood sampling will be performed twice in both groups, on
      admission, and 10 days after treatment. The following investigations will be carried out:
      complete blood picture, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF alpha),
      blood culture, Serum creatinine, Liver enzymes, and INR. A lumbar puncture will be performed
      when the treating physicians suspect meningitis. Patients in both groups will be observed
      along the duration of hospital admission to detect the outcome.

      Patients in the intervention group, receiving Montelukast sodium (Singulair), will be given
      at a dose according to body weight (1.5 kg to 2 kg, will be given 1.5 mg; greater than 2 kg,
      will be given 2 mg). This dose was previously prescribed and given to preterm neonates
      suffered from bronchopulmonary dysplasia by Kim et al. (2015). Four mg of the drug will be
      dissolved in four ml milk and 1.5 - 2 ml milk only will be given once daily at 9 pm via an
      orogastric tube or by oral administration for 10 days. Along the period of NICU admission,
      patients receiving Montelukast will be closely observed for the development of any of its
      side effects that including "diarrhea, colic, vomiting, fever or cough" (Adelsberg et al.,
      2005).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in serum tumor necrosis factor (TNF) Alpha level
time frame: Measured twice: on admission and 10 days after receiving therapy
description: Change in serum level of TNF alpha is assessed by the difference between the admission level and its level at 10 days after receiving the therapy.
measure: The duration of NICU admission
time frame: Counting the total duration of NICU admission
description: the total duration of NICU admission
measure: Change in serum C-reactive protein (CRP) level
time frame: Measured twice: on admission and 10 days after receiving therapy
description: Serum C-reactive protein (CRP) level will be measured on admission and compare its level with the level at 10 days after receiving therapy. It will be measured in both groups
measure: Patients improvement, deterioration (Clinically and laboratory) or death
time frame: determined at 10 days after receiving therapy
description: Patients are considered 1.improved when manifested clinically by no respiratory distress, normal temperature, no oxygen support, no inotropes, alert, not lethargic, tolerate feeding, increasing in body weight and laboratory by normal CBC , normal CRP, Culture negative. 2. Partially improved if patient still on intravenous fluid therapy, still on oxygen support, still on inotropes, CRP decreasing but still positive, and CBC still abnormal. 3. Deteriorated if developed complication as coagulopathy, septic shock or MODS.
measure: use of positive pressure ventilation and its duration
time frame: determined at 10 days after receiving therapy
description: use of positive pressure ventilation (receiving mechanical ventilation or CPAP) and the duration
measure: Duration of use of inotropes
time frame: determined at 10 days after receiving therapy
description: duration of inotropes (dopamine, epinephrine, norepinephrine)
arm group label: Intervention group
arm group type: Experimental
description: The intervention group will receive Montelukast Sodium for 10 days in addition to the conventional antibiotic therapy regimen and other supportive measures according to the policy of neonatal units and patients' needs. Montelukast sodium will be given at a dose according to body weight (1.5 kg to 2 kg, will be given 1.5 mg; greater than 2 kg, 2 mg will be given) this dose was calculated according to ( Kim et al. (2015). Four mg of the drug will be dissolved in four ml milk and 1.5 - 2 ml milk only will be given once daily at 9 pm via an orogastric tube or by oral administration for 10 days and patients of this group will be closely observed for development of Montelukast side effects as "diarrhea, colic, vomiting, fever and cough" (Adelsberg et al. 2005).
arm group label: Control group
arm group type: No Intervention
description: The control group will receive antibiotics and other supportive measures according to the policy of neonatal units and patients' needs.
intervention type: Drug
intervention name: Montelukast Sodium
description: Montelukast sodium (Singulair) will be given at a dose according to body weight. Four mg of the drug will be dissolved in four ml milk and the dose will be given once daily at 9 pm for 10 days.
arm group label: Intervention group
other name: Singulair
criteria: 
gender: All
minimum age: 1 Day
maximum age: 30 Days
healthy volunteers: No
last name: Hanan A El-Halaby
role: Principal Investigator
affiliation: Mansoura University Children Hospital, Gomhuria street, 35116 Mansoura, Egypt
facility: 
country: Egypt
citation: van Adelsberg J, Moy J, Wei LX, Tozzi CA, Knorr B, Reiss TF. Safety, tolerability, and exploratory efficacy of montelukast in 6- to 24-month-old patients with asthma. Curr Med Res Opin. 2005 Jun;21(6):971-9. doi: 10.1185/030079905X48456.
PMID: 15969897
citation: Kim SB, Lee JH, Lee J, Shin SH, Eun HS, Lee SM, Sohn JA, Kim HS, Choi BM, Park MS, Park KI, Namgung R, Park MS. The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia. Korean J Pediatr. 2015 Sep;58(9):347-53. doi: 10.3345/kjp.2015.58.9.347. Epub 2015 Sep 21.
PMID: 26512261
responsible party type: Principal Investigator
investigator affiliation: Mansoura University Children Hospital
investigator full name: Hanan El-Halaby
investigator title: Principal investigator
mesh term: Sepsis
mesh term: Toxemia
mesh term: Neonatal Sepsis
mesh term: Montelukast