<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/NCT03306095</url>
  </required_header>
  <id_info>
    <org_study_id>EVLF2017</org_study_id>
    <nct_id>NCT03306095</nct_id>
  </id_info>
  <brief_title>Comparison of Early Vs Delayed Feeding on Rebleeding Following Endoscopic Ligation for Acute Esophageal Variceal Bleeding</brief_title>
  <acronym>EVLF</acronym>
  <official_title>Comparison of Early Vs Delayed Feeding on Rebleeding Following Endoscopic Ligation for Acute Esophageal Variceal Bleeding</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dayanand Medical College and Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dayanand Medical College and Hospital</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>
      Following endoscopic therapy of variceal bleeding, the issue of when to refeed these patients&#xD;
      has rarely been investigated. This may imply that feeding is generally regarded as a&#xD;
      negligible factor in the management of bleeding varices. On the other hand, it is usually&#xD;
      believed that systematic fasting is required in case of patients with upper gastrointestinal&#xD;
      bleeding.&#xD;
&#xD;
      Some researchers in their studies demonstrated that immediate refeeding has similar outcomes&#xD;
      to delayed refeeding among patients with low risk of nonvariceal bleeding. The situation of&#xD;
      variceal bleeding is quite different from that of peptic ulcer bleeding as demonstrated by&#xD;
      studies of other researchers who made a review on feeding of patients with upper&#xD;
      gastrointestinal bleeding, and recommended that feeding should be delayed for at least 48&#xD;
      hours after endoscopic therapy because early refeeding may cause a shift in blood flow to the&#xD;
      splanchnic circulation, which in turn could lead to an increase in pressure and an increased&#xD;
      risk of rebleeding from the varices.&#xD;
&#xD;
      The other important reason of delay in feeding may be ascribed to the fear of occurrence of&#xD;
      early rebleeding induced by refeeding. In addition, repeated endoscopic examination and&#xD;
      therapy may be required in patients with very early rebleeding. The decision to delay feeding&#xD;
      is usually based on clinicians 'experience or experts' opinion rather than evidence based.&#xD;
      That is why we planned this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There has not been much studies conducted to address this issue however most of the&#xD;
      recommendations are made in view of preventing any complications following procedures.&#xD;
      Stiegmann and Goff 4 were the first to employ EVL to treat esophageal varices. They did not&#xD;
      mention any specific restriction of feeding on patients receiving band ligation however they&#xD;
      did mentioned that following the band ligation of varices, the ligated varices and tissues&#xD;
      may evoke transient dysphagia to solid food.5 A study conducted by Gin Ho Lo et al 6&#xD;
      demonstrated that early feeding with a liquid diet in conscious patients after successful&#xD;
      endoscopic therapy of varices can shorten the hospital stay. The two groups which were&#xD;
      created in this study were the early-feeding group and the delayed-feeding group. Patients in&#xD;
      the early-feeding group were asked to fast for only 4 hours following endoscopic treatment.&#xD;
      Subsequently, a liquid diet (fruit juice, soybean juice, milk, rice in liquid form) was&#xD;
      instituted for 3 days. Additionally, &lt;500 cc intravenous fluid with proper electrolyte&#xD;
      supplement per day was administered. Thereafter, a soft diet was provided for 3 days, after&#xD;
      which a regular diet was resumed since the seventh day after endoscopic treatment. Patients&#xD;
      in the delayed-feeding group were asked to absolutely fast for 48 hours after endoscopic&#xD;
      treatment, and 1500 cc/day intravenous fluids (normal saline or glucose water) with proper&#xD;
      electrolytes were administered for 2 days. After 2 days of fasting, a liquid diet was given&#xD;
      for 1 day, and subsequently, a soft diet was given for 3 days, and then a regular diet was&#xD;
      instituted on the seventh day after endoscopic treatment. If rebleeding occurred within 7&#xD;
      days of endoscopic therapy, patients in both groups were again asked to fast for 48 hours,&#xD;
      and then put on a liquid diet for 1 day followed by a soft diet for 4 days.&#xD;
&#xD;
      Treatment failure was defined as failure to control acute bleeding episodes or very early&#xD;
      rebleeding or death within 5 days. Failure to control acute variceal bleeding was defined as&#xD;
      the occurrence of any of the following events within 48 hours of enrollment, based on the&#xD;
      modified criteria of the Baveno III consensus:7 (1) fresh hematemesis after enrollment; (2)&#xD;
      sudden onset of reduction in blood pressure of _20 mmHg and/or an increase in pulse rate of&#xD;
      20 beats/minute with 2 g drop in hemoglobin; (3) transfusion of four units of blood required&#xD;
      to increase the hematocrit to above 27% or hemoglobin to above 9 g/dL; and (4) death. Very&#xD;
      early rebleeding was defined as when the criteria for failure to control acute variceal&#xD;
      bleeding occurred between 48 hours and 120 hours after enrollment in patients achieving&#xD;
      control of acute bleeding. Control of acute bleeding (initial hemostasis) was defined as when&#xD;
      the criteria for failure did not occur within 48 hours of enrollment. A 5-day hemostasis was&#xD;
      defined as when the criteria for failure to control acute variceal bleeding and very early&#xD;
      rebleeding did not occur within 5 days of enrollment. A nasogastric tube was not routinely&#xD;
      inserted after initial endoscopy.&#xD;
&#xD;
      The rebleeding rates associated with EVL varied greatly between studies, and rates ranging&#xD;
      from 2% to 54% have been recorded.8,9 Aside from other reasons, this discrepancy is very&#xD;
      likely to be related to the variation in timing of refeeding after EVL. However, this factor&#xD;
      was rarely mentioned in the methodology of these studies A review article by Xavier&#xD;
      He´buterne 10 concluded that In patients hospitalized for acute upper gastrointestinal&#xD;
      bleeding due to an ulcer with high risk of rebleeding (Forrest I-IIb) or with variceal&#xD;
      bleeding it is recommended to wait at least 48 h after endoscopic therapy before initiating&#xD;
      oral or enteral feeding. In case of ulcer with low risk of rebleeding (Forrest IIc and III)&#xD;
      or in patients with gastritis, Mallory-Weiss, oesophagitis, or angiodysplasia, there is no&#xD;
      need to delay refeeding, and they can be fed as soon as tolerated. Understanding the cause of&#xD;
      the diagnosis is always necessary to adapt nutrition in patients with upper gastrointestinal&#xD;
      bleeding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2, 2017</start_date>
  <completion_date type="Actual">July 16, 2018</completion_date>
  <primary_completion_date type="Actual">May 1, 2018</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>2 Days</target_duration>
  <primary_outcome>
    <measure>Bleeding</measure>
    <time_frame>48 hour</time_frame>
    <description>Early Re bleed Rate versus delayed variceal re bleed rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>48 hour</time_frame>
    <description>Mortality rate following early and late feeding</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemostasis</measure>
    <time_frame>48 hour</time_frame>
    <description>Hemostasis</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">200</enrollment>
  <condition>Acute Gastroesophageal Variceal Bleeding</condition>
  <arm_group>
    <arm_group_label>Early refeeding group</arm_group_label>
    <description>Food Intake by patient with in 4 hours i.e &lt;4 hours after the EVL procedure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed refeeding group</arm_group_label>
    <description>Food Intake by patient with in 4 hours i.e &gt; 4 hours after the EVL procedure</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Early refeeding group</intervention_name>
    <description>Food Intake by patient with in 4 hours i.e &lt;4 hours after the EVL procedure</description>
    <arm_group_label>Delayed refeeding group</arm_group_label>
    <arm_group_label>Early refeeding group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Delayed refeeding group</intervention_name>
    <description>Food Intake by patient after 4 hours i.e &gt; 4 hours after the EVL procedure</description>
    <arm_group_label>Delayed refeeding group</arm_group_label>
    <arm_group_label>Early refeeding group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Based on earlier study done by Gin-Ho Lo et al where the prevalence of UGI bleed in early&#xD;
        refeeding group was 33 % and late refeeding group was 10 % a sample size required to detect&#xD;
        any significant difference was found to be 88. Adding to which 10 % of attrition a total&#xD;
        sample size of 100 was taken.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Presence of Portal Hypertension with or without cirrhosis.&#xD;
&#xD;
          2. 18 and 80 years of age.&#xD;
&#xD;
          3. Prophylactic EVL&#xD;
&#xD;
          4. EVL was performed as maintenance treatment for Past history of bleeding varices&#xD;
&#xD;
          5. Emergency endoscopic EVL for acutely bleeding varices.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Septicemia&#xD;
&#xD;
          2. Patients with advanced hepatocellular carcinoma (HCC)&#xD;
&#xD;
          3. Failure to control variceal bleeding by emergency endoscopic therapy.&#xD;
&#xD;
          4. Uncooperative patient&#xD;
&#xD;
          5. Patient with endotracheal intubation.&#xD;
&#xD;
          6. Ever received EIS or EVL within 1 month prior to index bleeding.&#xD;
&#xD;
          7. Child Pugh's scores &gt;13.&#xD;
&#xD;
          8. Presence of Overt hepatic encephalopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sandeep Singh Sidhu</name>
      <address>
        <city>Ludhiana</city>
        <state>Punjab</state>
        <zip>141001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <results_reference>
    <citation>Hebuterne X, Vanbiervliet G. Feeding the patients with upper gastrointestinal bleeding. Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):197-201. doi: 10.1097/MCO.0b013e3283436dc5.</citation>
    <PMID>21252654</PMID>
  </results_reference>
  <results_reference>
    <citation>Laine L, Cohen H, Brodhead J, Cantor D, Garcia F, Mosquera M. Prospective evaluation of immediate versus delayed refeeding and prognostic value of endoscopy in patients with upper gastrointestinal hemorrhage. Gastroenterology. 1992 Jan;102(1):314-6. doi: 10.1016/0016-5085(92)91816-m.</citation>
    <PMID>1727765</PMID>
  </results_reference>
  <results_reference>
    <citation>Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60; quiz 361. doi: 10.1038/ajg.2011.480. Epub 2012 Feb 7.</citation>
    <PMID>22310222</PMID>
  </results_reference>
  <results_reference>
    <citation>Lo GH, Lin CW, Hsu YC. A controlled trial of early versus delayed feeding following ligation in the control of acute esophageal variceal bleeding. J Chin Med Assoc. 2015 Nov;78(11):642-7. doi: 10.1016/j.jcma.2015.07.004. Epub 2015 Sep 2.</citation>
    <PMID>26341455</PMID>
  </results_reference>
  <results_reference>
    <citation>Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010 Mar 4;362(9):823-32. doi: 10.1056/NEJMra0901512. No abstract available. Erratum In: N Engl J Med. 2011 Feb 3;364(5):490. Dosage error in article text.</citation>
    <PMID>20200386</PMID>
  </results_reference>
  <results_reference>
    <citation>Lo GH. Management of acute esophageal variceal hemorrhage. Kaohsiung J Med Sci. 2010 Feb;26(2):55-67. doi: 10.1016/s1607-551x(10)70009-7.</citation>
    <PMID>20123593</PMID>
  </results_reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>October 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 10, 2017</study_first_posted>
  <last_update_submitted>July 30, 2018</last_update_submitted>
  <last_update_submitted_qc>July 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dayanand Medical College and Hospital</investigator_affiliation>
    <investigator_full_name>Prof. Sandeep S Sidhu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</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/NCT03306095
org study id: EVLF2017
nct id: NCT03306095
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Following endoscopic therapy of variceal bleeding, the issue of when to refeed these patients
      has rarely been investigated. This may imply that feeding is generally regarded as a
      negligible factor in the management of bleeding varices. On the other hand, it is usually
      believed that systematic fasting is required in case of patients with upper gastrointestinal
      bleeding.

      Some researchers in their studies demonstrated that immediate refeeding has similar outcomes
      to delayed refeeding among patients with low risk of nonvariceal bleeding. The situation of
      variceal bleeding is quite different from that of peptic ulcer bleeding as demonstrated by
      studies of other researchers who made a review on feeding of patients with upper
      gastrointestinal bleeding, and recommended that feeding should be delayed for at least 48
      hours after endoscopic therapy because early refeeding may cause a shift in blood flow to the
      splanchnic circulation, which in turn could lead to an increase in pressure and an increased
      risk of rebleeding from the varices.

      The other important reason of delay in feeding may be ascribed to the fear of occurrence of
      early rebleeding induced by refeeding. In addition, repeated endoscopic examination and
      therapy may be required in patients with very early rebleeding. The decision to delay feeding
      is usually based on clinicians 'experience or experts' opinion rather than evidence based.
      That is why we planned this study.
There has not been much studies conducted to address this issue however most of the
      recommendations are made in view of preventing any complications following procedures.
      Stiegmann and Goff 4 were the first to employ EVL to treat esophageal varices. They did not
      mention any specific restriction of feeding on patients receiving band ligation however they
      did mentioned that following the band ligation of varices, the ligated varices and tissues
      may evoke transient dysphagia to solid food.5 A study conducted by Gin Ho Lo et al 6
      demonstrated that early feeding with a liquid diet in conscious patients after successful
      endoscopic therapy of varices can shorten the hospital stay. The two groups which were
      created in this study were the early-feeding group and the delayed-feeding group. Patients in
      the early-feeding group were asked to fast for only 4 hours following endoscopic treatment.
      Subsequently, a liquid diet (fruit juice, soybean juice, milk, rice in liquid form) was
      instituted for 3 days. Additionally, <500 cc intravenous fluid with proper electrolyte
      supplement per day was administered. Thereafter, a soft diet was provided for 3 days, after
      which a regular diet was resumed since the seventh day after endoscopic treatment. Patients
      in the delayed-feeding group were asked to absolutely fast for 48 hours after endoscopic
      treatment, and 1500 cc/day intravenous fluids (normal saline or glucose water) with proper
      electrolytes were administered for 2 days. After 2 days of fasting, a liquid diet was given
      for 1 day, and subsequently, a soft diet was given for 3 days, and then a regular diet was
      instituted on the seventh day after endoscopic treatment. If rebleeding occurred within 7
      days of endoscopic therapy, patients in both groups were again asked to fast for 48 hours,
      and then put on a liquid diet for 1 day followed by a soft diet for 4 days.

      Treatment failure was defined as failure to control acute bleeding episodes or very early
      rebleeding or death within 5 days. Failure to control acute variceal bleeding was defined as
      the occurrence of any of the following events within 48 hours of enrollment, based on the
      modified criteria of the Baveno III consensus:7 (1) fresh hematemesis after enrollment; (2)
      sudden onset of reduction in blood pressure of _20 mmHg and/or an increase in pulse rate of
      20 beats/minute with 2 g drop in hemoglobin; (3) transfusion of four units of blood required
      to increase the hematocrit to above 27% or hemoglobin to above 9 g/dL; and (4) death. Very
      early rebleeding was defined as when the criteria for failure to control acute variceal
      bleeding occurred between 48 hours and 120 hours after enrollment in patients achieving
      control of acute bleeding. Control of acute bleeding (initial hemostasis) was defined as when
      the criteria for failure did not occur within 48 hours of enrollment. A 5-day hemostasis was
      defined as when the criteria for failure to control acute variceal bleeding and very early
      rebleeding did not occur within 5 days of enrollment. A nasogastric tube was not routinely
      inserted after initial endoscopy.

      The rebleeding rates associated with EVL varied greatly between studies, and rates ranging
      from 2% to 54% have been recorded.8,9 Aside from other reasons, this discrepancy is very
      likely to be related to the variation in timing of refeeding after EVL. However, this factor
      was rarely mentioned in the methodology of these studies A review article by Xavier
      He´buterne 10 concluded that In patients hospitalized for acute upper gastrointestinal
      bleeding due to an ulcer with high risk of rebleeding (Forrest I-IIb) or with variceal
      bleeding it is recommended to wait at least 48 h after endoscopic therapy before initiating
      oral or enteral feeding. In case of ulcer with low risk of rebleeding (Forrest IIc and III)
      or in patients with gastritis, Mallory-Weiss, oesophagitis, or angiodysplasia, there is no
      need to delay refeeding, and they can be fed as soon as tolerated. Understanding the cause of
      the diagnosis is always necessary to adapt nutrition in patients with upper gastrointestinal
      bleeding.
observational model: Case-Control
time perspective: Prospective
measure: Bleeding
time frame: 48 hour
description: Early Re bleed Rate versus delayed variceal re bleed rate
measure: Mortality
time frame: 48 hour
description: Mortality rate following early and late feeding
measure: Hemostasis
time frame: 48 hour
description: Hemostasis
arm group label: Early refeeding group
description: Food Intake by patient with in 4 hours i.e <4 hours after the EVL procedure
arm group label: Delayed refeeding group
description: Food Intake by patient with in 4 hours i.e > 4 hours after the EVL procedure
intervention type: Other
intervention name: Early refeeding group
description: Food Intake by patient with in 4 hours i.e <4 hours after the EVL procedure
arm group label: Delayed refeeding group
arm group label: Early refeeding group
intervention type: Other
intervention name: Delayed refeeding group
description: Food Intake by patient after 4 hours i.e > 4 hours after the EVL procedure
arm group label: Delayed refeeding group
arm group label: Early refeeding group
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: India
citation: Hebuterne X, Vanbiervliet G. Feeding the patients with upper gastrointestinal bleeding. Curr Opin Clin Nutr Metab Care. 2011 Mar;14(2):197-201. doi: 10.1097/MCO.0b013e3283436dc5.
PMID: 21252654
citation: Laine L, Cohen H, Brodhead J, Cantor D, Garcia F, Mosquera M. Prospective evaluation of immediate versus delayed refeeding and prognostic value of endoscopy in patients with upper gastrointestinal hemorrhage. Gastroenterology. 1992 Jan;102(1):314-6. doi: 10.1016/0016-5085(92)91816-m.
PMID: 1727765
citation: Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60; quiz 361. doi: 10.1038/ajg.2011.480. Epub 2012 Feb 7.
PMID: 22310222
citation: Lo GH, Lin CW, Hsu YC. A controlled trial of early versus delayed feeding following ligation in the control of acute esophageal variceal bleeding. J Chin Med Assoc. 2015 Nov;78(11):642-7. doi: 10.1016/j.jcma.2015.07.004. Epub 2015 Sep 2.
PMID: 26341455
citation: Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010 Mar 4;362(9):823-32. doi: 10.1056/NEJMra0901512. No abstract available. Erratum In: N Engl J Med. 2011 Feb 3;364(5):490. Dosage error in article text.
PMID: 20200386
citation: Lo GH. Management of acute esophageal variceal hemorrhage. Kaohsiung J Med Sci. 2010 Feb;26(2):55-67. doi: 10.1016/s1607-551x(10)70009-7.
PMID: 20123593
responsible party type: Principal Investigator
investigator affiliation: Dayanand Medical College and Hospital
investigator full name: Prof. Sandeep S Sidhu
investigator title: Professor
mesh term: Hemorrhage