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/NCT06027970</url>
    </required_header>
    <id_info>
      <org_study_id>IEC-INT/2023/Study-865</org_study_id>
      <nct_id>NCT06027970</nct_id>
    </id_info>
    <brief_title>Efficacy of Continuous Terlipressin Therapy After Endoscopic Variceal Ligation</brief_title>
    <acronym>TERLEVL</acronym>
    <official_title>Efficacy of Continuous Terlipressin Therapy After Endoscopic Variceal Ligation in Acute Variceal Haemorrhage: A Randomised Control Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Postgraduate Institute of Medical Education and Research</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Postgraduate Institute of Medical Education and Research</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>
        Upper gastrointestinal (UGI) bleed of variceal origin is a common medical emergency. Prompt&#xD;
        endoscopic variceal ligation (EVL) is therapeutic as well as diagnostic. Terlipressin, a&#xD;
        vasopressin analog (intravenous, 2 mg q 4 hourly), is widely used promptly in any suspicious&#xD;
        cases of variceal haemorrhage (VH) before endoscopic intervention, along with volume and&#xD;
        blood resuscitative measures.&#xD;
  &#xD;
        As per guideline, after EVL Terlipressin therapy (1 mg IV q 4 hourly) is advised to continue&#xD;
        for 2-5 day to prevent re-bleed and mortality [1]. But the prolong use of Terlipressin is not&#xD;
        completely safe as well as it is expensive also in resource constraint setting. At present,&#xD;
        no randomized control clinical trial (RCT) is available to prove the efficacy of post-EVL&#xD;
        Terlipressin therapy in preventing re-bleed and mortality in acute variceal haemorrhage.&#xD;
  &#xD;
        During the post marketing surveillance Terlipressin therapy was found to be associated with&#xD;
        life threatening complication like cardiac arrhythmia, myocardial ischemia, critical&#xD;
        vasoconstriction of peripheral as well as internal organ leading to ischemia or gangrene,&#xD;
        severe hyponatremia, hypertension, fluid overload and pulmonary oedema (2-4).&#xD;
  &#xD;
        So the justification of continuing Terlipressin for 5 days after EVL is questionable, as the&#xD;
        haemostasis is primarily achieved by EVL and the risk versus benefit of Trelipressin therapy&#xD;
        after EVL is still unknown. Continue IV Terlipressin therapy also prolongs in-hospital care&#xD;
        causing further increase of health care burden.&#xD;
  &#xD;
        As per recently concluded institutional study, continuing Terlipressin after EVL in acute VH&#xD;
        did not prevent re-bleed or mortality, rather it increased the risk of ADR, duration of&#xD;
        hospital stay, in-hospital complications and cost of the therapy [5]. But the study was open&#xD;
        level with relatively smaller sample size.&#xD;
  &#xD;
        There is still lack of RCT on post-EVL Terlipressin therapy, regarding its efficacy in&#xD;
        preventing re-bleed and mortality. So, we have planned this study to evaluate the efficacy of&#xD;
        continuous Terlipressin therapy after EVL, in acute VH.&#xD;
  &#xD;
        It will be a double blind randomized controlled clinical trial. The study will be carried out&#xD;
        in the 2 arms; denoting the duration of Terlipressin therapy after EVL. Participant with&#xD;
        acute VH will be randomized into two study groups after successful EVL.&#xD;
  &#xD;
        The treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days&#xD;
        and the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly&#xD;
        instead of Terlipressin for 2 days. Both the group will receive standard care of therapy and&#xD;
        will be followed up for 8 weeks. The participants and the recruiter/PI will be unaware of&#xD;
        intervention (terlipressin or NS) receiving.&#xD;
  &#xD;
        The study will enlighten us regarding efficacy of continuous Terlipressin therapy after EVL&#xD;
        to prevent re- bleed and mortality in acute VH. The study will also generate significant data&#xD;
        regarding adverse drug events (ADE) and cost effectiveness or pharmaco- economics of continue&#xD;
        Terlipressin therapy after EVL.&#xD;
  &#xD;
        In the Indian population there is no study to determine the role gene related to variceal&#xD;
        bleed or re-bleed. Endothelial dysfunction is the major contributor for the development of&#xD;
        portal hypertension and subsequent varices formation in patient with cirrhosis. Development&#xD;
        of blood vessel and endothelial function, endothelial proliferation and neoangiogenesis are&#xD;
        regulated by vascular endothelial growth factor (VEGF) family genes. In a recently published&#xD;
        study, VEGF C(+405)G(rs2010963) single nucleotide polymorphism (SNP) genotype was found to be&#xD;
        associated with higher risk of esophageal and gastric varices and bleeding [10]. Since VEGF&#xD;
        is the major factor to endothelial proliferation and neoangiogenesis. So, in this study, as a&#xD;
        secondary objective, we will also try to explore the association of VEGF genotype with&#xD;
        variceal bleed/ re-bleed and mortality.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <phase>Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Re-bleed</measure>
      <time_frame>7 days</time_frame>
      <description>Re-bleed is defined as any significant UGI haemorrhage after EVL, leading to repeat endoscopy, haemodynamic instability and significant drop of haemoglobin requiring blood transfusion.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mortality</measure>
      <time_frame>7 days</time_frame>
      <description>Incidence of episode of mortality</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of hospital stay</measure>
      <time_frame>1 week</time_frame>
      <description>Number of days of stay in the hospital</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>need for blood transfusions</measure>
      <time_frame>1 week</time_frame>
      <description>After successful EVL, requirement of blood transfusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse drug reaction (ADR)</measure>
      <time_frame>1 week</time_frame>
      <description>Incidence of adverse drug reaction (ADR)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">165</enrollment>
    <condition>Variceal Hemorrhage</condition>
    <arm_group>
      <arm_group_label>Treatment</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>After successful Endoscopic variceal ligation (EVL) the treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days. Both the group will receive standard care of therapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>After successful Endoscopic variceal ligation (EVL) the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly instead of Terlipressin for 2 days. Both the group will receive standard care of therapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Terlipressin</intervention_name>
      <description>After successful Endoscopic variceal ligation (EVL) The treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days</description>
      <arm_group_label>Treatment</arm_group_label>
      <other_name>Standard care of therapy</other_name>
      <other_name>Endoscopic variceal ligation (EVL)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>0.9% normal saline (NS)</intervention_name>
      <description>After successful Endoscopic variceal ligation (EVL) the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly instead of Terlipressin for 2 days</description>
      <arm_group_label>Control</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Irrespective of gender&#xD;
  &#xD;
            -  age ≥ 18 years&#xD;
  &#xD;
            -  all the patients with endoscopy proven acute VH with successful EVL done&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients not receiving pre-EVL Terlipressin therapy&#xD;
  &#xD;
            -  not achieving haemostasis during EVL&#xD;
  &#xD;
            -  EVL done beyond 48 hours of admission because of hemodynamic instability or&#xD;
               encephalopathy&#xD;
  &#xD;
            -  Patients with chronic kidney disease&#xD;
  &#xD;
            -  Patients with pregnancy&#xD;
  &#xD;
            -  Patients who are receiving blood thinners like anti-platelets, anti-coagulation agents&#xD;
               within 4 weeks of presentation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Deba P Dhibar, MD</last_name>
      <phone>9530881462</phone>
      <email>drdeba_prasad@yahoo.co.in</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Internal Medicine, Post Graduate Institute of Medical Education and Research,</name>
        <address>
          <city>Chandigarh</city>
          <zip>160012</zip>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>P</last_name>
        <phone>+911722756670</phone>
        <email>pgimerinternalmed@hotmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
      <investigator_full_name>Deba Prasad Dhibar</investigator_full_name>
      <investigator_title>Associate 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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Terlipressin</mesh_term>
    </intervention_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/NCT06027970
  org study id: IEC-INT/2023/Study-865
  nct id: NCT06027970
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Upper gastrointestinal (UGI) bleed of variceal origin is a common medical emergency. Prompt
        endoscopic variceal ligation (EVL) is therapeutic as well as diagnostic. Terlipressin, a
        vasopressin analog (intravenous, 2 mg q 4 hourly), is widely used promptly in any suspicious
        cases of variceal haemorrhage (VH) before endoscopic intervention, along with volume and
        blood resuscitative measures.
  
        As per guideline, after EVL Terlipressin therapy (1 mg IV q 4 hourly) is advised to continue
        for 2-5 day to prevent re-bleed and mortality [1]. But the prolong use of Terlipressin is not
        completely safe as well as it is expensive also in resource constraint setting. At present,
        no randomized control clinical trial (RCT) is available to prove the efficacy of post-EVL
        Terlipressin therapy in preventing re-bleed and mortality in acute variceal haemorrhage.
  
        During the post marketing surveillance Terlipressin therapy was found to be associated with
        life threatening complication like cardiac arrhythmia, myocardial ischemia, critical
        vasoconstriction of peripheral as well as internal organ leading to ischemia or gangrene,
        severe hyponatremia, hypertension, fluid overload and pulmonary oedema (2-4).
  
        So the justification of continuing Terlipressin for 5 days after EVL is questionable, as the
        haemostasis is primarily achieved by EVL and the risk versus benefit of Trelipressin therapy
        after EVL is still unknown. Continue IV Terlipressin therapy also prolongs in-hospital care
        causing further increase of health care burden.
  
        As per recently concluded institutional study, continuing Terlipressin after EVL in acute VH
        did not prevent re-bleed or mortality, rather it increased the risk of ADR, duration of
        hospital stay, in-hospital complications and cost of the therapy [5]. But the study was open
        level with relatively smaller sample size.
  
        There is still lack of RCT on post-EVL Terlipressin therapy, regarding its efficacy in
        preventing re-bleed and mortality. So, we have planned this study to evaluate the efficacy of
        continuous Terlipressin therapy after EVL, in acute VH.
  
        It will be a double blind randomized controlled clinical trial. The study will be carried out
        in the 2 arms; denoting the duration of Terlipressin therapy after EVL. Participant with
        acute VH will be randomized into two study groups after successful EVL.
  
        The treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days
        and the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly
        instead of Terlipressin for 2 days. Both the group will receive standard care of therapy and
        will be followed up for 8 weeks. The participants and the recruiter/PI will be unaware of
        intervention (terlipressin or NS) receiving.
  
        The study will enlighten us regarding efficacy of continuous Terlipressin therapy after EVL
        to prevent re- bleed and mortality in acute VH. The study will also generate significant data
        regarding adverse drug events (ADE) and cost effectiveness or pharmaco- economics of continue
        Terlipressin therapy after EVL.
  
        In the Indian population there is no study to determine the role gene related to variceal
        bleed or re-bleed. Endothelial dysfunction is the major contributor for the development of
        portal hypertension and subsequent varices formation in patient with cirrhosis. Development
        of blood vessel and endothelial function, endothelial proliferation and neoangiogenesis are
        regulated by vascular endothelial growth factor (VEGF) family genes. In a recently published
        study, VEGF C(+405)G(rs2010963) single nucleotide polymorphism (SNP) genotype was found to be
        associated with higher risk of esophageal and gastric varices and bleeding [10]. Since VEGF
        is the major factor to endothelial proliferation and neoangiogenesis. So, in this study, as a
        secondary objective, we will also try to explore the association of VEGF genotype with
        variceal bleed/ re-bleed and mortality.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Re-bleed
  time frame: 7 days
  description: Re-bleed is defined as any significant UGI haemorrhage after EVL, leading to repeat endoscopy, haemodynamic instability and significant drop of haemoglobin requiring blood transfusion.
  measure: Mortality
  time frame: 7 days
  description: Incidence of episode of mortality
  measure: Duration of hospital stay
  time frame: 1 week
  description: Number of days of stay in the hospital
  measure: need for blood transfusions
  time frame: 1 week
  description: After successful EVL, requirement of blood transfusion
  measure: Adverse drug reaction (ADR)
  time frame: 1 week
  description: Incidence of adverse drug reaction (ADR)
  arm group label: Treatment
  arm group type: Active Comparator
  description: After successful Endoscopic variceal ligation (EVL) the treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days. Both the group will receive standard care of therapy.
  arm group label: Control
  arm group type: Placebo Comparator
  description: After successful Endoscopic variceal ligation (EVL) the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly instead of Terlipressin for 2 days. Both the group will receive standard care of therapy.
  intervention type: Drug
  intervention name: Terlipressin
  description: After successful Endoscopic variceal ligation (EVL) The treatment group will receive injection Terlipressin (1 mg IV bolus q 4 hourly) for 2 days
  arm group label: Treatment
  other name: Standard care of therapy
  other name: Endoscopic variceal ligation (EVL)
  intervention type: Other
  intervention name: 0.9% normal saline (NS)
  description: After successful Endoscopic variceal ligation (EVL) the control group will receive 10 ml of 0.9% normal saline (NS) IV bolus q 4 hourly instead of Terlipressin for 2 days
  arm group label: Control
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Deba P Dhibar, MD
  phone: 9530881462
  email: drdeba_prasad@yahoo.co.in
  facility: 
  contact: 
  country: India
  responsible party type: Principal Investigator
  investigator affiliation: Postgraduate Institute of Medical Education and Research
  investigator full name: Deba Prasad Dhibar
  investigator title: Associate Professor
  mesh term: Hemorrhage
  mesh term: Terlipressin
  sharing ipd: No