xml: <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/NCT06035848</url>
    </required_header>
    <id_info>
      <org_study_id>01-2021</org_study_id>
      <nct_id>NCT06035848</nct_id>
    </id_info>
    <brief_title>Components of Metabolic Derangement and Paracentesis for Determination of Surgery in Preterm Neonates With Necrotizing Enterocolitis.</brief_title>
    <official_title>Components of Metabolic Derangement and Paracentesis for Determination of Surgery in Preterm Neonates With Necrotizing Enterocolitis.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Gerardo Fernández Ortega</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Instituto Materno Infantil del Estado de México</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Instituto de Salud del Estado de México</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Hospital General de Mexico</source>
    <oversight_info>
      <has_dmc>No</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 aim of this clinical trial is to associate paracentesis with positive metabolic&#xD;
        derangement components for surgical determination in preterm infants with necrotizing&#xD;
        enterocolitis. The main questions it aims to answer are:&#xD;
  &#xD;
          -  are the combination of metabolic derangement components and paracentesis good indicators&#xD;
             for determining early surgery in preterm patients with necrotizing enterocolitis?&#xD;
  &#xD;
          -  With the use of the previously mentioned indicators, can mortality in these patients be&#xD;
             reduced? Participants will undergo determination of the 7 parameters of the metabolic&#xD;
             deterioration components and those with three or more positive points will undergo&#xD;
             paracentesis and if this is also positive, it will be determined that the patient&#xD;
             requires surgical management.&#xD;
  &#xD;
        The researchers will compare with a control group to see the differences in surgical&#xD;
        variables (length of necrotic bowel, length of viable bowel, need for intestinal diversion&#xD;
        and surgical reintervention) and mortality.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Controlled, randomized, double-blind clinical trial approved by the hospital's Ethics and&#xD;
        Research Committee, subject to the Declaration of Helsinki. This study follows the CONSORT&#xD;
        trial reporting guidelines. Patients younger than 37 weeks of gestation, with NEC stage IIa&#xD;
        or greater according to Bell criteria were included.&#xD;
  &#xD;
        Two groups of patients were formed (Control and Intervention), randomization was based on a&#xD;
        randomization sequence generated using the Graphard 2021 program.&#xD;
  &#xD;
        Control group: determination of surgery in a conventional manner according to Bell's criteria&#xD;
        (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.&#xD;
  &#xD;
        Intervention Group: CMD measurement every 3rd day, it was considered positive when 3 or more&#xD;
        points were present. These patients underwent paracentesis and if it was positive (faecal&#xD;
        aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery&#xD;
        was made.&#xD;
  &#xD;
        Both groups received the same pre- and post-surgical medical management by neonatology.&#xD;
  &#xD;
        As a safety criterion, it was defined that when a surgeon considered that a neonate had an&#xD;
        indication for surgery, in spite of not meeting the criteria previously indicated for each&#xD;
        group, the surgical intervention would be performed.&#xD;
  &#xD;
        The diagnosis, implementation of the randomization to each group, and blood sampling were&#xD;
        performed by the neonatology staff, the surgical research team being blinded; paracentesis&#xD;
        was performed by a pediatric surgeon in the patient's crib with asepsis measures, antisepsis&#xD;
        with chlorhexidine, sedation and analgesia (fentanyl 2 to 4 mcg /kg/dose), 1% lidocaine&#xD;
        infiltration at the puncture site (iliac fossa right), a 22 G punzocath and a 10 ml syringe&#xD;
        were used .&#xD;
  &#xD;
        Follow-up was performed until the patient was discharged or died. Mortality was the dependent&#xD;
        variable. The time from the patient's admission to the study until surgery was considered;&#xD;
        during exploratory laparotomy, the length of intestinal necrosis, length of viable intestine,&#xD;
        need for intestinal bypass, surgical intervention performed, and surgical reintervention were&#xD;
        determined. In addition, fasting days and parenteral nutrition (TPN) were quantified.&#xD;
  &#xD;
        Sample size. Based on the calculation for the difference of two proportions, a size of 31&#xD;
        patients per group was obtained, with a mortality difference of 30%, one-tailed, alpha of 5%,&#xD;
        and statistical power of 80%. In June 2022, it was decided to carry out an intermediate&#xD;
        analysis to assess the benefit or harm of the intervention, determined by the p value ˂ 0.05&#xD;
        in the dependent variable.&#xD;
  &#xD;
        Statistical analysis. Descriptive statistics with measures of central tendency and dispersion&#xD;
        were used. For qualitative variables frequencies and percentages, for quantitative variables&#xD;
        mean and standard deviation. The Shapiro-Wilk test was used to test normal distribution.&#xD;
  &#xD;
        For inferential statistics, group comparisons were performed using the χ2 test, Fisher's&#xD;
        exact test, Student's t test or Mann Whitney U test, according to the type and distribution&#xD;
        of the variable. The relative risk (RR) was obtained as a measure of association, with 95%&#xD;
        confidence interval (CI). In addition, a bivariate analysis was performed between mortality&#xD;
        and secondary variables. Statistical significance was established with a p-value &lt;0.05.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Terminated</overall_status>
    <why_stopped>
      In June 2022, it was decided to perform an intermediate analysis to assess the benefit or harm&#xD;
      of the intervention.&#xD;
    </why_stopped>
    <start_date type="Actual">February 1, 2021</start_date>
    <completion_date type="Actual">June 30, 2022</completion_date>
    <primary_completion_date type="Actual">May 31, 2022</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>The aim of this study was to determine an indication for early surgery in preterm neonates with necrotizing enterocolitis by using paracentesis in combination with the components of metabolic derangement compared to using the Bell´s criteria.&#xD;
  Two groups of patients were formed (Control and Intervention). Control group: determination of surgery in a conventional manner according to Bell's criteria (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.&#xD;
  Intervention Group: components of metabolic derangement measurement every 3rd day, it was considered positive when 3 or more points were present. These patients underwent paracentesis and if it was positive (faecal aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery was made.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The diagnosis, application of randomization to each group and blood sampling were performed by the neonatology staff, both the patients and the surgical team that provided care were blinded.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Mortality in preterm newborns with necrotizing enterocolitis</measure>
      <time_frame>Neonates were followed from the date of surgery until death or hospital discharge, whichever came first, evaluated up to 6 months.</time_frame>
      <description>The mortality of patients with necrotizing enterocolitis who required surgical management in both groups was determined.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">117</enrollment>
    <condition>Necrotizing Enterocolitis</condition>
    <arm_group>
      <arm_group_label>Intervention group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Components of metabolic derangement measurement every 3rd day, it was considered positive when 3 or more points were present. These patients underwent paracentesis and if it was positive (faecal aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery was made.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Determination of surgery in a conventional manner according to Bell's criteria (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Association of the components of metabolic derangement and paracentesis.</intervention_name>
      <description>In the intervention group were determined:&#xD;
  Components of metabolic derangement&#xD;
  Paracentesis. Determination of surgery: 3 positive points of the components of the metabolic derangement and a positive paracentesis.&#xD;
  The components of the metabolic derangement are the 7 parameters described by Tepas: positive blood culture, metabolic acidosis, neutropenia, bandemia, thrombocytopenia, hyponatremia and hypotension, being considered positive when 3 or more parameters are present.&#xD;
  Paracentesis was considered positive according to Kosloske's criteria: obtaining more than 0.5ml of serohematic fluid, Gram-positive fluid and obtaining fecal material.&#xD;
  Both groups had the same pre, trans and postoperative care.</description>
      <arm_group_label>Intervention group</arm_group_label>
      <other_name>MD7: components of metabolic derangement</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bell's criteria: pneumoperitoneum</intervention_name>
      <description>In the control group, the surgery was determined according to Bell's criteria, in the presence of radiographic pneumoperitoneum as an absolute indication for surgery.</description>
      <arm_group_label>Control group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients equal to or less than 36.6 weeks gestation, with a diagnosis of NEC stage II&#xD;
               A or greater according to Bell criteria.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with a history of gastroschisis, suspected Hirschsprung's disease. Patients&#xD;
               who do not give authorization for participation.&#xD;
  &#xD;
          Elimination criteria:&#xD;
  &#xD;
          Patients who during follow-up died due to some other condition. Patients who during the&#xD;
          study declined to participate. Patients who in the surgical findings had data of&#xD;
          Spontaneous Intestinal Perforation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Gerardo Fernández, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Not affiliated</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Hospital de Ginecología y Obstetricia IMIEM</name>
        <address>
          <city>Toluca</city>
          <zip>50170</zip>
          <country>Mexico</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Mexico</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 4, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Hospital General de Mexico</investigator_affiliation>
      <investigator_full_name>Gerardo Fernández Ortega</investigator_full_name>
      <investigator_title>Pediatric Surgery Specialty Coordinator / Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Surgery</keyword>
    <keyword>New born</keyword>
    <keyword>Pediatrics</keyword>
    <keyword>Mortality</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Enterocolitis</mesh_term>
      <mesh_term>Enterocolitis, Necrotizing</mesh_term>
      <mesh_term>Metabolic Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06035848
  org study id: 01-2021
  nct id: NCT06035848
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The aim of this clinical trial is to associate paracentesis with positive metabolic
        derangement components for surgical determination in preterm infants with necrotizing
        enterocolitis. The main questions it aims to answer are:
  
          -  are the combination of metabolic derangement components and paracentesis good indicators
             for determining early surgery in preterm patients with necrotizing enterocolitis?
  
          -  With the use of the previously mentioned indicators, can mortality in these patients be
             reduced? Participants will undergo determination of the 7 parameters of the metabolic
             deterioration components and those with three or more positive points will undergo
             paracentesis and if this is also positive, it will be determined that the patient
             requires surgical management.
  
        The researchers will compare with a control group to see the differences in surgical
        variables (length of necrotic bowel, length of viable bowel, need for intestinal diversion
        and surgical reintervention) and mortality.
  Controlled, randomized, double-blind clinical trial approved by the hospital's Ethics and
        Research Committee, subject to the Declaration of Helsinki. This study follows the CONSORT
        trial reporting guidelines. Patients younger than 37 weeks of gestation, with NEC stage IIa
        or greater according to Bell criteria were included.
  
        Two groups of patients were formed (Control and Intervention), randomization was based on a
        randomization sequence generated using the Graphard 2021 program.
  
        Control group: determination of surgery in a conventional manner according to Bell's criteria
        (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.
  
        Intervention Group: CMD measurement every 3rd day, it was considered positive when 3 or more
        points were present. These patients underwent paracentesis and if it was positive (faecal
        aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery
        was made.
  
        Both groups received the same pre- and post-surgical medical management by neonatology.
  
        As a safety criterion, it was defined that when a surgeon considered that a neonate had an
        indication for surgery, in spite of not meeting the criteria previously indicated for each
        group, the surgical intervention would be performed.
  
        The diagnosis, implementation of the randomization to each group, and blood sampling were
        performed by the neonatology staff, the surgical research team being blinded; paracentesis
        was performed by a pediatric surgeon in the patient's crib with asepsis measures, antisepsis
        with chlorhexidine, sedation and analgesia (fentanyl 2 to 4 mcg /kg/dose), 1% lidocaine
        infiltration at the puncture site (iliac fossa right), a 22 G punzocath and a 10 ml syringe
        were used .
  
        Follow-up was performed until the patient was discharged or died. Mortality was the dependent
        variable. The time from the patient's admission to the study until surgery was considered;
        during exploratory laparotomy, the length of intestinal necrosis, length of viable intestine,
        need for intestinal bypass, surgical intervention performed, and surgical reintervention were
        determined. In addition, fasting days and parenteral nutrition (TPN) were quantified.
  
        Sample size. Based on the calculation for the difference of two proportions, a size of 31
        patients per group was obtained, with a mortality difference of 30%, one-tailed, alpha of 5%,
        and statistical power of 80%. In June 2022, it was decided to carry out an intermediate
        analysis to assess the benefit or harm of the intervention, determined by the p value ˂ 0.05
        in the dependent variable.
  
        Statistical analysis. Descriptive statistics with measures of central tendency and dispersion
        were used. For qualitative variables frequencies and percentages, for quantitative variables
        mean and standard deviation. The Shapiro-Wilk test was used to test normal distribution.
  
        For inferential statistics, group comparisons were performed using the χ2 test, Fisher's
        exact test, Student's t test or Mann Whitney U test, according to the type and distribution
        of the variable. The relative risk (RR) was obtained as a measure of association, with 95%
        confidence interval (CI). In addition, a bivariate analysis was performed between mortality
        and secondary variables. Statistical significance was established with a p-value <0.05.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The aim of this study was to determine an indication for early surgery in preterm neonates with necrotizing enterocolitis by using paracentesis in combination with the components of metabolic derangement compared to using the Bell´s criteria.
  Two groups of patients were formed (Control and Intervention). Control group: determination of surgery in a conventional manner according to Bell's criteria (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.
  Intervention Group: components of metabolic derangement measurement every 3rd day, it was considered positive when 3 or more points were present. These patients underwent paracentesis and if it was positive (faecal aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery was made.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: The diagnosis, application of randomization to each group and blood sampling were performed by the neonatology staff, both the patients and the surgical team that provided care were blinded.
  measure: Mortality in preterm newborns with necrotizing enterocolitis
  time frame: Neonates were followed from the date of surgery until death or hospital discharge, whichever came first, evaluated up to 6 months.
  description: The mortality of patients with necrotizing enterocolitis who required surgical management in both groups was determined.
  arm group label: Intervention group
  arm group type: Experimental
  description: Components of metabolic derangement measurement every 3rd day, it was considered positive when 3 or more points were present. These patients underwent paracentesis and if it was positive (faecal aspiration, serous fluid with Gram + staining, or serohematic fluid) the decision for surgery was made.
  arm group label: Control group
  arm group type: Active Comparator
  description: Determination of surgery in a conventional manner according to Bell's criteria (absolute indication: pneumoperitoneum), with radiographic surveillance every 6 hours.
  intervention type: Procedure
  intervention name: Association of the components of metabolic derangement and paracentesis.
  description: In the intervention group were determined:
  Components of metabolic derangement
  Paracentesis. Determination of surgery: 3 positive points of the components of the metabolic derangement and a positive paracentesis.
  The components of the metabolic derangement are the 7 parameters described by Tepas: positive blood culture, metabolic acidosis, neutropenia, bandemia, thrombocytopenia, hyponatremia and hypotension, being considered positive when 3 or more parameters are present.
  Paracentesis was considered positive according to Kosloske's criteria: obtaining more than 0.5ml of serohematic fluid, Gram-positive fluid and obtaining fecal material.
  Both groups had the same pre, trans and postoperative care.
  arm group label: Intervention group
  other name: MD7: components of metabolic derangement
  intervention type: Procedure
  intervention name: Bell's criteria: pneumoperitoneum
  description: In the control group, the surgery was determined according to Bell's criteria, in the presence of radiographic pneumoperitoneum as an absolute indication for surgery.
  arm group label: Control group
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Gerardo Fernández, MD
  role: Principal Investigator
  affiliation: Not affiliated
  facility: 
  country: Mexico
  responsible party type: Sponsor-Investigator
  investigator affiliation: Hospital General de Mexico
  investigator full name: Gerardo Fernández Ortega
  investigator title: Pediatric Surgery Specialty Coordinator / Principal Investigator
  mesh term: Enterocolitis
  mesh term: Enterocolitis, Necrotizing
  mesh term: Metabolic Diseases
  sharing ipd: No