<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/NCT04437264</url>
  </required_header>
  <id_info>
    <org_study_id>2000027328</org_study_id>
    <nct_id>NCT04437264</nct_id>
  </id_info>
  <brief_title>Intermittent Versus Continuous Enteral Nutrition in Mechanically Ventilated Patients in the Medical Intensive Care Unit</brief_title>
  <official_title>Intermittent Versus Continuous Enteral Nutrition in Mechanically Ventilated Patients in the Medical Intensive Care Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</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>
      Evaluate effective delivery of goal nutrition with intermittent as compared with continuous&#xD;
      enteral nutrition schedules, as defined by percentage of recommended calories that patient&#xD;
      receives per day of interest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be approached and if the patient (or surrogate decision maker) is&#xD;
      interested, then consent will be obtained for participation in the study. The patient will&#xD;
      then be randomly assigned to receive usual care (continuous feeds) or intervention&#xD;
      (intermittent feeds, see details below). Randomization will occur via simple block&#xD;
      randomization within the REDCap software. Group assignment will not be revealed to the&#xD;
      clinical team until the decision to feed the patient has occurred and the actual feeding&#xD;
      order is entered. When the clinical team decides to initiate enteral nutrition, they will&#xD;
      place a nutrition consult order for tube feed recommendations. Nutrition consult will place&#xD;
      recommendations for both continuous feeding and for intermittent schedule, including enteral&#xD;
      nutrition formula and dosing. Prior to feeds being started, the patient's randomization&#xD;
      status will be revealed to the clinical team. The covering provider will then place the order&#xD;
      for enteral nutrition according to the nutritionist's recommendations for the correct feeding&#xD;
      schedule.&#xD;
&#xD;
      For patients randomized to continuous feeds, their enteral nutrition will be ordered and&#xD;
      delivered as per usual care and standard MICU procedure. Nutritionist will provide&#xD;
      recommendations for initiation rate, up titration schedule, and maintenance dosing to be&#xD;
      delivered continuously over 24 hours. Under usual care of ICU patients, our clinical&#xD;
      nutritionists provide a specified formula, a specified calorie goal, and a suggested&#xD;
      titration rate. This is typically 20 mL per hour to start with an increase in rate of 20 mL&#xD;
      per hour every 6 to 8 hours until the goal rate is achieved. Typical goal rates are in the&#xD;
      range of 60 to 80 mL per hour for 24 hours per day.&#xD;
&#xD;
      For patients randomized to the intervention group (intermittent feeds), they will receive&#xD;
      their enteral nutrition according to a research protocol schedule. This will involve the&#xD;
      total recommended feed volume divided into four equal volume &quot;meals.&quot; These will be delivered&#xD;
      at a rate of 400 cc/hr at 8:00, 12:00, 16:00, and 20:00. The up-titration schedule will be as&#xD;
      follows: first meal will be 100 mL, and the volume of each meal thereafter will be increased&#xD;
      by 100mL until patient is at goal volume (typically between 300 and 450 mL). There are no&#xD;
      formula or diets that are inappropriate to be administered on an intermittent feed schedule.&#xD;
      The intervention will not change formula selection or total calorie goals. It will only&#xD;
      change the schedule of feeding. For all patients, regardless of feeding schedule, the&#xD;
      Kangaroo E-Pump will be used to deliver enteral nutrition, and the above rate and volume&#xD;
      parameters can be programmed in.&#xD;
&#xD;
      There will be no change in delivery of enteral free water or medications. This schedule will&#xD;
      be determined by nursing and clinical care team, as is the current standard of care. To&#xD;
      assure correct ordering of intermittent feeds and the insulin prior to each meal, an EPIC&#xD;
      orderset with prepopulated instructions will be developed.&#xD;
&#xD;
      If there are no signs of or clinical concerns for intolerance, patients will continue to&#xD;
      receive enteral nutrition according to assigned schedule until they are extubated or until&#xD;
      enteral nutrition is discontinued.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 7, 2020</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The care team and study staff in the ICU will be aware of arm assignment. Study staff abstracting outcome data will be blinded to arm assignement.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Recommended calories</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>percentage of recommended calories that patient receives per day of interest during study period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with aspiration</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>percentage of patients experiencing aspiration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients experiencing intolerance of feeding</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>percentage of patients experiencing intolerance of feeding including nausea, vomiting, diarrhea, ileus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>feasibility: proportion complete protocol</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>percentage of patients assigned to intervention (ie intermittent feeding protocol) that remain on study protocol for study period of interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>delirium</measure>
    <time_frame>intubation day 1 until 14 days later</time_frame>
    <description>number of delirium and coma free days out of 14 following intubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>urine 6-sulfatoxymelatonin acrophase</measure>
    <time_frame>day 1 to 3 following initiation of feeds</time_frame>
    <description>Urine 6-sulfatoxymelatonin acrophase defined as the time of fitted peak 6-sulfatoxymelatonin from fitting a cosine curve to hourly urine aMT6s levels will be determined daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>maximum glucose</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>highest glucose per day of interest</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>minimum glucose</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>lowest glucose per day of interest</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insulin usage</measure>
    <time_frame>Intubation day 1 to intubation day 10</time_frame>
    <description>number of insulin units used per day (composite of short and long acting formulations)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Enteral Feeding</condition>
  <condition>Nutrition Disorders</condition>
  <arm_group>
    <arm_group_label>Intermittent feed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be assigned to receive intermittent enteral feeding protocol. They will receive four equal volume feeds at 8:00, 12:00, 16:00, and 20:00 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous feeds</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be assigned to receive continuous enteral feeding protocol. Typical goal rates are in the range of 60 to 80 mL per hour for 24 hours per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Intermittent feed participant</intervention_name>
    <description>Patients will be assigned to receive intermittent enteral feeding protocol. They will receive four equal volume feeds at 8:00, 12:00, 16:00, and 20:00 hours.</description>
    <arm_group_label>Intermittent feed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Continuous feeds participant</intervention_name>
    <description>Patients will be assigned to receive continuous enteral feeding protocol. Typical goal rates are in the range of 60 to 80 mL per hour for 24 hours per day.</description>
    <arm_group_label>Continuous feeds</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          -  MICU Yale New Haven Hospital&#xD;
&#xD;
          -  Age &gt;= 18 years old.&#xD;
&#xD;
          -  Patients mechanically ventilated via endotracheal tube&#xD;
&#xD;
          -  Patients intubated within 72 hours of hospital admission&#xD;
&#xD;
          -  First intubation of current hospitalization&#xD;
&#xD;
          -  First MICU admission of current hospitalization&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
        • Patient has opted out of research participation via institutional patient portal.&#xD;
&#xD;
        At significant risk for gastrointestinal intolerance of intermittent bolus feeds:&#xD;
&#xD;
          -  Prior upper gastrointestinal surgery that alters proximal GI anatomy (including but&#xD;
             not limited to gastric bypass surgery, gastric banding, complete or partial&#xD;
             gastrectomy, Whipple procedure; of note, appendectomy and cholecystectomy are not&#xD;
             exclusion criteria.&#xD;
&#xD;
          -  Structural gastrointestinal obstruction (such as tumor).&#xD;
&#xD;
          -  Chronic enteral nutrition (prior to current admission).&#xD;
&#xD;
          -  History of significant esophageal dysmotility (history of GERD is acceptable) or&#xD;
             clinically significant GE junction incompetence&#xD;
&#xD;
          -  Unable to have head of bed elevated at least 30 degrees while intubated and being fed&#xD;
             (this is standard protocol).&#xD;
&#xD;
          -  Enteral access terminates post-pyloric (ie nasojejunal or jejunostomy tubes are to be&#xD;
             excluded) or unable to place gastric tube for access. (The clinical team will&#xD;
             determine type of tube placement. As this is particularly selected by intensivists for&#xD;
             patients at higher aspiration risk, this tube enteral access exclusion de facto&#xD;
             excludes patients at high aspiration risk.)&#xD;
&#xD;
          -  History of small bowel obstruction or ileus on current admission or within last 1&#xD;
             month.&#xD;
&#xD;
          -  History of gastroparesis.&#xD;
&#xD;
          -  Percutaneous gastrostomy tube or tracheostomy.&#xD;
&#xD;
          -  History of ongoing aspiration as determined by a speech medicine specialist or other&#xD;
             medical professional or a patent who required adjustment of diet (e.g., thickening of&#xD;
             liquids) prior to hospitalization.&#xD;
&#xD;
          -  History of significant esophageal dysmotility (history of GERD is acceptable) or&#xD;
             clinically significant GE junction incompetence&#xD;
&#xD;
        Other Exclusion Criteria:&#xD;
&#xD;
          -  At risk of refeeding syndrome.&#xD;
&#xD;
          -  Pregnant patients.&#xD;
&#xD;
          -  Patients receiving neuromuscular blockade.&#xD;
&#xD;
          -  Patients with glycemic emergency (HHNK, DKA, severe hypoglycemia resulting in MICU&#xD;
             admission) or patients controlling their sugar / insulin dosing via continuous glucose&#xD;
             monitoring&#xD;
&#xD;
          -  Post cardiac arrest (on current admission).&#xD;
&#xD;
          -  Received &gt;= 6 hours of enteral nutrition (regardless of volume) at the time of&#xD;
             screening and team is able to consent / enroll / initiate intermittent feed within an&#xD;
             additional 2 hours.&#xD;
&#xD;
          -  Plan for extubation within 24 hours.&#xD;
&#xD;
          -  Not English-speaking.&#xD;
&#xD;
          -  Patients otherwise excluded by the treating physician.&#xD;
&#xD;
          -  Retrospective exclusion: patients who initially met eligibility criteria, but no&#xD;
             nutrition consult (i.e., decision to initiate feeds by clinical providers) placed&#xD;
             within 72 hours of intubation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melissa P Knauert, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melissa P Knauert, MD, PhD</last_name>
    <phone>203.785.4163</phone>
    <email>melissa.knauert@yale.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Taylor A Intihar, BS</last_name>
    <phone>203.785.3207</phone>
    <email>taylor.intihar@yale.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Yale New Haven Hospital, York Street Campus</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MICU Director</last_name>
    </contact>
    <investigator>
      <last_name>Melissa P Knauert, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>January 24, 2023</last_update_submitted>
  <last_update_submitted_qc>January 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nutrition Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>De-identified individual participant data can be made available upon request.</ipd_description>
  </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/NCT04437264
org study id: 2000027328
nct id: NCT04437264
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Evaluate effective delivery of goal nutrition with intermittent as compared with continuous
      enteral nutrition schedules, as defined by percentage of recommended calories that patient
      receives per day of interest.
Eligible patients will be approached and if the patient (or surrogate decision maker) is
      interested, then consent will be obtained for participation in the study. The patient will
      then be randomly assigned to receive usual care (continuous feeds) or intervention
      (intermittent feeds, see details below). Randomization will occur via simple block
      randomization within the REDCap software. Group assignment will not be revealed to the
      clinical team until the decision to feed the patient has occurred and the actual feeding
      order is entered. When the clinical team decides to initiate enteral nutrition, they will
      place a nutrition consult order for tube feed recommendations. Nutrition consult will place
      recommendations for both continuous feeding and for intermittent schedule, including enteral
      nutrition formula and dosing. Prior to feeds being started, the patient's randomization
      status will be revealed to the clinical team. The covering provider will then place the order
      for enteral nutrition according to the nutritionist's recommendations for the correct feeding
      schedule.

      For patients randomized to continuous feeds, their enteral nutrition will be ordered and
      delivered as per usual care and standard MICU procedure. Nutritionist will provide
      recommendations for initiation rate, up titration schedule, and maintenance dosing to be
      delivered continuously over 24 hours. Under usual care of ICU patients, our clinical
      nutritionists provide a specified formula, a specified calorie goal, and a suggested
      titration rate. This is typically 20 mL per hour to start with an increase in rate of 20 mL
      per hour every 6 to 8 hours until the goal rate is achieved. Typical goal rates are in the
      range of 60 to 80 mL per hour for 24 hours per day.

      For patients randomized to the intervention group (intermittent feeds), they will receive
      their enteral nutrition according to a research protocol schedule. This will involve the
      total recommended feed volume divided into four equal volume "meals." These will be delivered
      at a rate of 400 cc/hr at 8:00, 12:00, 16:00, and 20:00. The up-titration schedule will be as
      follows: first meal will be 100 mL, and the volume of each meal thereafter will be increased
      by 100mL until patient is at goal volume (typically between 300 and 450 mL). There are no
      formula or diets that are inappropriate to be administered on an intermittent feed schedule.
      The intervention will not change formula selection or total calorie goals. It will only
      change the schedule of feeding. For all patients, regardless of feeding schedule, the
      Kangaroo E-Pump will be used to deliver enteral nutrition, and the above rate and volume
      parameters can be programmed in.

      There will be no change in delivery of enteral free water or medications. This schedule will
      be determined by nursing and clinical care team, as is the current standard of care. To
      assure correct ordering of intermittent feeds and the insulin prior to each meal, an EPIC
      orderset with prepopulated instructions will be developed.

      If there are no signs of or clinical concerns for intolerance, patients will continue to
      receive enteral nutrition according to assigned schedule until they are extubated or until
      enteral nutrition is discontinued.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The care team and study staff in the ICU will be aware of arm assignment. Study staff abstracting outcome data will be blinded to arm assignement.
measure: Recommended calories
time frame: Intubation day 1 to intubation day 10
description: percentage of recommended calories that patient receives per day of interest during study period
measure: Percentage of patients with aspiration
time frame: Intubation day 1 to intubation day 10
description: percentage of patients experiencing aspiration
measure: Percentage of patients experiencing intolerance of feeding
time frame: Intubation day 1 to intubation day 10
description: percentage of patients experiencing intolerance of feeding including nausea, vomiting, diarrhea, ileus
measure: feasibility: proportion complete protocol
time frame: Intubation day 1 to intubation day 10
description: percentage of patients assigned to intervention (ie intermittent feeding protocol) that remain on study protocol for study period of interest.
measure: delirium
time frame: intubation day 1 until 14 days later
description: number of delirium and coma free days out of 14 following intubation
measure: urine 6-sulfatoxymelatonin acrophase
time frame: day 1 to 3 following initiation of feeds
description: Urine 6-sulfatoxymelatonin acrophase defined as the time of fitted peak 6-sulfatoxymelatonin from fitting a cosine curve to hourly urine aMT6s levels will be determined daily
measure: maximum glucose
time frame: Intubation day 1 to intubation day 10
description: highest glucose per day of interest
measure: minimum glucose
time frame: Intubation day 1 to intubation day 10
description: lowest glucose per day of interest
measure: insulin usage
time frame: Intubation day 1 to intubation day 10
description: number of insulin units used per day (composite of short and long acting formulations)
arm group label: Intermittent feed
arm group type: Experimental
description: Patients will be assigned to receive intermittent enteral feeding protocol. They will receive four equal volume feeds at 8:00, 12:00, 16:00, and 20:00 hours.
arm group label: Continuous feeds
arm group type: Experimental
description: Patients will be assigned to receive continuous enteral feeding protocol. Typical goal rates are in the range of 60 to 80 mL per hour for 24 hours per day.
intervention type: Dietary Supplement
intervention name: Intermittent feed participant
description: Patients will be assigned to receive intermittent enteral feeding protocol. They will receive four equal volume feeds at 8:00, 12:00, 16:00, and 20:00 hours.
arm group label: Intermittent feed
intervention type: Dietary Supplement
intervention name: Continuous feeds participant
description: Patients will be assigned to receive continuous enteral feeding protocol. Typical goal rates are in the range of 60 to 80 mL per hour for 24 hours per day.
arm group label: Continuous feeds
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Melissa P Knauert, MD, PhD
role: Principal Investigator
affiliation: Yale University
last name: Melissa P Knauert, MD, PhD
phone: 203.785.4163
email: melissa.knauert@yale.edu
last name: Taylor A Intihar, BS
phone: 203.785.3207
email: taylor.intihar@yale.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Nutrition Disorders
sharing ipd: No
ipd description: De-identified individual participant data can be made available upon request.