<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/NCT02187978</url>
  </required_header>
  <id_info>
    <org_study_id>LHMC/098/2012/ETEF</org_study_id>
    <nct_id>NCT02187978</nct_id>
  </id_info>
  <brief_title>Early Total Enteral Feeding Versus Conventional Enteral Feeding in Stable Very Low Birth Weight Infants</brief_title>
  <official_title>Comparison of Early Total Enteral Feeding (ETEF) Versus Conventional Enteral Feeding (CEF) in Stable Very Low Birth Weight (VLBW) Infants - A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lady Hardinge Medical College</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lady Hardinge Medical College</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the effect of early total oral feeding versus&#xD;
      conventional oral feeding in stable VLBW infants. In current clinical practice, the&#xD;
      introduction of oral feeds for VLBW infants is often preceded by a period of fasting or&#xD;
      minimal feeding because of fear of necrotizing enterocolitis (NEC). However, this may be&#xD;
      associated with potential disadvantages and increased infectious and metabolic complications&#xD;
      related to prolonged fasting and use of parenteral nutrition. The studies conducted till date&#xD;
      have shown better outcomes and improved postnatal growth with early initiation and fast&#xD;
      advancements of feeds. It is still unclear whether stable VLBW babies can tolerate total oral&#xD;
      feeds on day 1 of life. No such study has been conducted on early total oral feeding but&#xD;
      observational work in our unit has shown it to be safe without any increased incidence of&#xD;
      feed intolerance or NEC. In view of the uncertainties regarding feeding protocols in VLBW&#xD;
      infants all over the world, the investigators decided to assess the effect of early total&#xD;
      enteral feeding in stable VLBW infants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preterm VLBW infants often have negligible intrauterine reserves of nutrition along with a&#xD;
      host of medical conditions postbirth including respiratory distress syndrome, hypoxia,&#xD;
      hypotension, acidosis, infection and surgery. These conditions increase the metabolic energy&#xD;
      requirements and nutrient needs of preterm babies. They require more specialised nutrition&#xD;
      because of their faster growth rates; to correct the growth faltering post birth and to&#xD;
      attain appropriate weight gain. Delayed postnatal growth due to inappropriate nutrition in&#xD;
      early period leads to long term cognitive impairment and decreased school performance.&#xD;
      Additional impediments to growth are high degree of biochemical and physiological immaturity&#xD;
      of gastro intestinal tract with an immature immune system.&#xD;
&#xD;
      In current clinical practice, the introduction of progressive enteral feeds for preterm VLBW&#xD;
      infants is often preceded by a period of enteral fasting or minimal enteral nutrition to&#xD;
      decrease the incidence of NEC. However, there may also be potential disadvantages associated&#xD;
      with delayed introduction of progressive enteral feeds. Gastrointestinal hormone secretion&#xD;
      and motility is stimulated by enteral milk and hence delayed enteral feeding could diminish&#xD;
      the functional adaptation of the gastrointestinal tract. In addition, 'starving' the gut may&#xD;
      be harmful increasing susceptibility to infection due to impaired barrier function by&#xD;
      intestinal epithelium. Parenteral nutrition (PN), though having an important role in early&#xD;
      stabilization by allowing early calorie intake and preventing catabolism, is associated with&#xD;
      significant risks of infectious and metabolic complications thereby increasing mortality and&#xD;
      morbidity, prolonging hospital stay, and adversely affecting growth and development. As per&#xD;
      recent literature reviews, enteral feeding has many advantages including appropriate intake&#xD;
      of most nutrients. It also promotes growth and development of the gut and reduces the risk of&#xD;
      infection. It is therefore important to establish enteral feeding as early as is safely&#xD;
      possible. It has been argued that the risk of NEC should not be considered in isolation of&#xD;
      these other potential clinical outcomes when determining feeding policies and practices for&#xD;
      VLBW infants. A systematically conducted, randomized controlled trial is necessary to prove&#xD;
      or refute the benefits of early total enteral feeding and nutrition. Hence the purpose of&#xD;
      this prospective randomized controlled trial is to compare the benefits of early total&#xD;
      enteral feeding over conventional enteral feeding in terms of attainment of full feeds,&#xD;
      incidence of sepsis &amp; NEC and duration of hospital stay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">June 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>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Day of attaining 150mL/Kg of enteral feeds</measure>
    <time_frame>Till 45 days of age</time_frame>
    <description>Full enteral feeds are defined as oral feeds at 150ml/Kg and sustaining it for 24 hrs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Episodes of feed intolerance</measure>
    <time_frame>Till 30 days of age or discharge whichever is earlier</time_frame>
    <description>Feed intolerance defined as presence of 1 or more of the following&#xD;
Vomiting &gt;3 times during any 24 hr period&#xD;
Any episode of bile/ blood stained vomiting&#xD;
Abdominal girth (AG) increase &gt; 2cm between feeds with pre feed gastric aspirate &gt; 25% of pre feed volume (milk) or any amount hgic/bilious&#xD;
Abdominal wall erythema&#xD;
Gross blood in stools</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of Sepsis</measure>
    <time_frame>Till 30 days of age or discharge whichever is earlier</time_frame>
    <description>Incidence of suspect (Clinical setting with positive sepsis screen) and confirmed (Clinical setting with positive blood culture) sepsis in the two groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of Hospital Stay</measure>
    <time_frame>Till 45 days of age</time_frame>
    <description>The total duration of hospital stay till discharge alive from hospital will be calculated in completed number of days</description>
  </other_outcome>
  <other_outcome>
    <measure>Mean weight at one month of age</measure>
    <time_frame>one month of age</time_frame>
    <description>The difference in mean weight in grams at one month of age between the neonates of the two groups</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Nutrition of Preterm Infants</condition>
  <arm_group>
    <arm_group_label>Early total enteral feeding (ETEF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Feeding will be initiated on D1 with 80ml/kg/day of expressed breast milk or LBW formula milk.&#xD;
No intravenous fluid will be provided. Feeds will be advanced till 150ml/kg/day is attained.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional enteral feeding (CEF)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Feeding will be initiated on D1of life with 20ml/kg of expressed breast milk or LBW formula milk.&#xD;
Remaining requirement as intravenous fluids. Feeds advanced by 20ml/kg/day for next 2 days and then 30ml/kg/day for the next three days until 150ml/kg/day is reached.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Early total enteral feeding (ETEF)</intervention_name>
    <description>In ETEF Group total required volume of fluid will be administered as oral feeds and no intravenous fluid will be given. Feeds will be started at 80 mL/kg and increased till 150ml/kg is attained.</description>
    <arm_group_label>Early total enteral feeding (ETEF)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional enteral feeding (CEF)</intervention_name>
    <description>CEF Group will receive some feed and some Intravenous fluids. Feeds will be slowly increased from 20 mL/kg on day 1 till full feeds 150ml/kg is attained on day 6 of life.</description>
    <arm_group_label>Conventional enteral feeding (CEF)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infants with gestational age between 28-34 weeks &amp; hemodynamically stable preterm VLBW&#xD;
             neonates (B Wt. 1000-1499g) defined as&#xD;
&#xD;
          -  No asphyxia(not required resuscitation beyond initial steps)&#xD;
&#xD;
          -  No significant respiratory distress at randomization (Not requiring respiratory&#xD;
             support)&#xD;
&#xD;
          -  No clinical evidence of shock at the time of randomization (not requiring vasopressor&#xD;
             support)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Major Congenital malformation&#xD;
&#xD;
          -  Refusal of consent&#xD;
&#xD;
          -  AREDF in utero&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Minutes</minimum_age>
    <maximum_age>120 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sushma Nangia, MD,DM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lady Hardinge Medical College &amp; Kalawati Saran Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lady Hardinge Medical College</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>September 26, 2015</last_update_submitted>
  <last_update_submitted_qc>September 26, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 29, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lady Hardinge Medical College</investigator_affiliation>
    <investigator_full_name>Sushma Nangia, M.D.</investigator_full_name>
    <investigator_title>Dr Sushma Nangia, Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Early total enteral feeding (ETEF)</keyword>
  <keyword>Conventional enteral feeding (CEF)</keyword>
  <keyword>VLBW infants</keyword>
  <keyword>NEC</keyword>
  <keyword>Preterm infants</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Birth Weight</mesh_term>
  </condition_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/NCT02187978
org study id: LHMC/098/2012/ETEF
nct id: NCT02187978
lead sponsor: 
has dmc: Yes
The purpose of this study is to compare the effect of early total oral feeding versus
      conventional oral feeding in stable VLBW infants. In current clinical practice, the
      introduction of oral feeds for VLBW infants is often preceded by a period of fasting or
      minimal feeding because of fear of necrotizing enterocolitis (NEC). However, this may be
      associated with potential disadvantages and increased infectious and metabolic complications
      related to prolonged fasting and use of parenteral nutrition. The studies conducted till date
      have shown better outcomes and improved postnatal growth with early initiation and fast
      advancements of feeds. It is still unclear whether stable VLBW babies can tolerate total oral
      feeds on day 1 of life. No such study has been conducted on early total oral feeding but
      observational work in our unit has shown it to be safe without any increased incidence of
      feed intolerance or NEC. In view of the uncertainties regarding feeding protocols in VLBW
      infants all over the world, the investigators decided to assess the effect of early total
      enteral feeding in stable VLBW infants.
Preterm VLBW infants often have negligible intrauterine reserves of nutrition along with a
      host of medical conditions postbirth including respiratory distress syndrome, hypoxia,
      hypotension, acidosis, infection and surgery. These conditions increase the metabolic energy
      requirements and nutrient needs of preterm babies. They require more specialised nutrition
      because of their faster growth rates; to correct the growth faltering post birth and to
      attain appropriate weight gain. Delayed postnatal growth due to inappropriate nutrition in
      early period leads to long term cognitive impairment and decreased school performance.
      Additional impediments to growth are high degree of biochemical and physiological immaturity
      of gastro intestinal tract with an immature immune system.

      In current clinical practice, the introduction of progressive enteral feeds for preterm VLBW
      infants is often preceded by a period of enteral fasting or minimal enteral nutrition to
      decrease the incidence of NEC. However, there may also be potential disadvantages associated
      with delayed introduction of progressive enteral feeds. Gastrointestinal hormone secretion
      and motility is stimulated by enteral milk and hence delayed enteral feeding could diminish
      the functional adaptation of the gastrointestinal tract. In addition, 'starving' the gut may
      be harmful increasing susceptibility to infection due to impaired barrier function by
      intestinal epithelium. Parenteral nutrition (PN), though having an important role in early
      stabilization by allowing early calorie intake and preventing catabolism, is associated with
      significant risks of infectious and metabolic complications thereby increasing mortality and
      morbidity, prolonging hospital stay, and adversely affecting growth and development. As per
      recent literature reviews, enteral feeding has many advantages including appropriate intake
      of most nutrients. It also promotes growth and development of the gut and reduces the risk of
      infection. It is therefore important to establish enteral feeding as early as is safely
      possible. It has been argued that the risk of NEC should not be considered in isolation of
      these other potential clinical outcomes when determining feeding policies and practices for
      VLBW infants. A systematically conducted, randomized controlled trial is necessary to prove
      or refute the benefits of early total enteral feeding and nutrition. Hence the purpose of
      this prospective randomized controlled trial is to compare the benefits of early total
      enteral feeding over conventional enteral feeding in terms of attainment of full feeds,
      incidence of sepsis & NEC and duration of hospital stay.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Day of attaining 150mL/Kg of enteral feeds
time frame: Till 45 days of age
description: Full enteral feeds are defined as oral feeds at 150ml/Kg and sustaining it for 24 hrs
measure: Episodes of feed intolerance
time frame: Till 30 days of age or discharge whichever is earlier
description: Feed intolerance defined as presence of 1 or more of the following
Vomiting >3 times during any 24 hr period
Any episode of bile/ blood stained vomiting
Abdominal girth (AG) increase > 2cm between feeds with pre feed gastric aspirate > 25% of pre feed volume (milk) or any amount hgic/bilious
Abdominal wall erythema
Gross blood in stools
measure: Incidence of Sepsis
time frame: Till 30 days of age or discharge whichever is earlier
description: Incidence of suspect (Clinical setting with positive sepsis screen) and confirmed (Clinical setting with positive blood culture) sepsis in the two groups
measure: Duration of Hospital Stay
time frame: Till 45 days of age
description: The total duration of hospital stay till discharge alive from hospital will be calculated in completed number of days
measure: Mean weight at one month of age
time frame: one month of age
description: The difference in mean weight in grams at one month of age between the neonates of the two groups
arm group label: Early total enteral feeding (ETEF)
arm group type: Experimental
description: Feeding will be initiated on D1 with 80ml/kg/day of expressed breast milk or LBW formula milk.
No intravenous fluid will be provided. Feeds will be advanced till 150ml/kg/day is attained.
arm group label: Conventional enteral feeding (CEF)
arm group type: Active Comparator
description: Feeding will be initiated on D1of life with 20ml/kg of expressed breast milk or LBW formula milk.
Remaining requirement as intravenous fluids. Feeds advanced by 20ml/kg/day for next 2 days and then 30ml/kg/day for the next three days until 150ml/kg/day is reached.
intervention type: Other
intervention name: Early total enteral feeding (ETEF)
description: In ETEF Group total required volume of fluid will be administered as oral feeds and no intravenous fluid will be given. Feeds will be started at 80 mL/kg and increased till 150ml/kg is attained.
arm group label: Early total enteral feeding (ETEF)
intervention type: Other
intervention name: Conventional enteral feeding (CEF)
description: CEF Group will receive some feed and some Intravenous fluids. Feeds will be slowly increased from 20 mL/kg on day 1 till full feeds 150ml/kg is attained on day 6 of life.
arm group label: Conventional enteral feeding (CEF)
criteria: 
gender: All
minimum age: 30 Minutes
maximum age: 120 Hours
healthy volunteers: No
last name: Sushma Nangia, MD,DM
role: Principal Investigator
affiliation: Lady Hardinge Medical College & Kalawati Saran Children's Hospital
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Lady Hardinge Medical College
investigator full name: Sushma Nangia, M.D.
investigator title: Dr Sushma Nangia, Professor of Pediatrics
mesh term: Birth Weight