<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/NCT02975323</url>
  </required_header>
  <id_info>
    <org_study_id>20-2605/R&amp;D/HEC/12</org_study_id>
    <nct_id>NCT02975323</nct_id>
  </id_info>
  <brief_title>Doppler Ultrasound Hepatic Vein Waveform as a Non-invasive Tool in the Assessment of Severity of Portal Hypertension</brief_title>
  <acronym>DPH</acronym>
  <official_title>Doppler Ultrasound Hepatic Vein Waveform as a Non-invasive Tool in the Assessment of Severity of Portal Hypertension (DPH Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dow University of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Portal hypertension is the result of an increased hepatic vascular resistance and portal&#xD;
      inflow. The best established method to assess portal pressures is the determination of wedged&#xD;
      hepatic venous pressure gradient (HVPG). Ultrasound Doppler technique is non-invasive in the&#xD;
      assessment of portal hypertension as compared with invasive technique of measurement of the&#xD;
      hepatic venous pressure gradient (HVPG). Hemodynamic measurements (BP and pulse recording)&#xD;
      will be done and then patient will be given tablet Carvedilol 12.5 mg in a single dose and&#xD;
      wait till the time that 20% reduction in heart rate from the baseline occurs. Haemodynamic&#xD;
      measurements will be repeated to assess the acute response to beta-adrenoreceptor blocker&#xD;
      agent. The change in the HWF will be recorded post beta-adrenoreceptor blocker&#xD;
      administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ultrasound Doppler technique is non-invasive in the assessment of portal hypertension as&#xD;
      compared with invasive technique of measurement of the hepatic venous pressure gradient&#xD;
      (HVPG). The Doppler waveform of the hepatic vein in healthy subjects is normally triphasic&#xD;
      (two negative waves and one positive wave) because of central venous pressure variations due&#xD;
      to the cardiac cycle. The normal triphasic hepatic vein waveform is transformed into a&#xD;
      biphasic or monophasic waveform in patients with cirrhosis. A monophasic waveform has been&#xD;
      shown to correlate with a high Child-Pugh score and a poor survival rate.&#xD;
&#xD;
      Therefore, Hepatic vein waveform (HVWF) evaluation with Doppler US may be used as a&#xD;
      supplemental tool to assess the severity of Portal Hypertension and therapeutic response to&#xD;
      portal pressure lowering drugs in primary prophylaxis of variceal bleed in patients with&#xD;
      large oesophageal varices. There's one study which has looked into the same topic but it has&#xD;
      been conducted on alcoholic cirrhotics.&#xD;
&#xD;
      Doppler ultrasound is a non-invasive tool in the measurement of portal pressure in portal&#xD;
      hypertensive patients. Hemodynamic measurements (BP and pulse recording) will be done and&#xD;
      then patient will be given tablet Carvedilol 12.5 mg in a single dose and wait till the time&#xD;
      that 20% reduction in heart rate from the baseline occurs. Haemodynamic measurements will be&#xD;
      repeated to assess the acute response to beta-adrenoreceptor blocker agent. The change in the&#xD;
      HWF will be recorded post beta-adrenoreceptor blocker administration. This study will be a&#xD;
      validation and interventional study. It is an open labeled study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2014</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of Correlation of HWF as detected on doppler ultrasound (tri-, bi,- monophasic pattern) and HVPG (mm Hg) as assessed at hepatic vein catherization in the portal hypertensive patient .</measure>
    <time_frame>6 hours</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Portal Hypertension</condition>
  <arm_group>
    <arm_group_label>Single</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To administer Carvedilol 12.5 mg orally and measure Wedge pressure gradient in hepatic veins followed by change in hepatic vein wave form</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carvedilol</intervention_name>
    <description>Single dose of oral carvedilol 12.5 mg and wait till the time there's 20% reduction in hepatic wedge pressure gradient from the baseline.</description>
    <arm_group_label>Single</arm_group_label>
    <other_name>carveda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with cirrhosis and large varices (≥ 5mm) on screening endoscopy&#xD;
&#xD;
          -  Not known esophageal or gastric variceal bleed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Small esophageal varices (&lt;5 mm in size) on screening endoscopy&#xD;
&#xD;
          -  Hemodynamically unstable i.e. Blood pressure of &lt;90mmHg and tachycardia of &gt;100bpm.&#xD;
&#xD;
          -  Contraindication to Beta-blockers (Asthma, bradycardia, heart failure, allergy)&#xD;
&#xD;
          -  history of Esophageal or gastric variceal bleed in the past&#xD;
&#xD;
          -  Hepatocellular carcinoma or other metastatic malignancy.&#xD;
&#xD;
          -  Portal vein thrombosis (PVT) or Inferior venacaval (IVC) thrombosis&#xD;
&#xD;
          -  Congestive cardiac failure (CCF)&#xD;
&#xD;
          -  Renal failure or Hepatorenal syndrome (Creatine of &gt;1.5 mg/dl)&#xD;
&#xD;
          -  Previous allergy to IV contrast agent.&#xD;
&#xD;
          -  Lactating or Pregnant women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Syed Hasnain A Shah, M.D.</last_name>
    <phone>00922134864676</phone>
    <email>hasnain.alishah@aku.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Aga Khan University,</name>
      <address>
        <city>Karachi</city>
        <state>Sind</state>
        <zip>74800</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tasneem Khan, MBA</last_name>
      <phone>00922134864670</phone>
      <email>tasneem.khan@aku.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>December 2, 2016</last_update_submitted>
  <last_update_submitted_qc>December 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>Dr. Syed Hasnain Ali Shah</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>hepatic venous pressure gradient</keyword>
  <keyword>liver disease</keyword>
  <keyword>US Doppler waveform</keyword>
  <keyword>Cirrhosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Portal</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carvedilol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02975323
org study id: 20-2605/R&D/HEC/12
nct id: NCT02975323
lead sponsor: 
collaborator: 
has dmc: Yes
Portal hypertension is the result of an increased hepatic vascular resistance and portal
      inflow. The best established method to assess portal pressures is the determination of wedged
      hepatic venous pressure gradient (HVPG). Ultrasound Doppler technique is non-invasive in the
      assessment of portal hypertension as compared with invasive technique of measurement of the
      hepatic venous pressure gradient (HVPG). Hemodynamic measurements (BP and pulse recording)
      will be done and then patient will be given tablet Carvedilol 12.5 mg in a single dose and
      wait till the time that 20% reduction in heart rate from the baseline occurs. Haemodynamic
      measurements will be repeated to assess the acute response to beta-adrenoreceptor blocker
      agent. The change in the HWF will be recorded post beta-adrenoreceptor blocker
      administration.
Ultrasound Doppler technique is non-invasive in the assessment of portal hypertension as
      compared with invasive technique of measurement of the hepatic venous pressure gradient
      (HVPG). The Doppler waveform of the hepatic vein in healthy subjects is normally triphasic
      (two negative waves and one positive wave) because of central venous pressure variations due
      to the cardiac cycle. The normal triphasic hepatic vein waveform is transformed into a
      biphasic or monophasic waveform in patients with cirrhosis. A monophasic waveform has been
      shown to correlate with a high Child-Pugh score and a poor survival rate.

      Therefore, Hepatic vein waveform (HVWF) evaluation with Doppler US may be used as a
      supplemental tool to assess the severity of Portal Hypertension and therapeutic response to
      portal pressure lowering drugs in primary prophylaxis of variceal bleed in patients with
      large oesophageal varices. There's one study which has looked into the same topic but it has
      been conducted on alcoholic cirrhotics.

      Doppler ultrasound is a non-invasive tool in the measurement of portal pressure in portal
      hypertensive patients. Hemodynamic measurements (BP and pulse recording) will be done and
      then patient will be given tablet Carvedilol 12.5 mg in a single dose and wait till the time
      that 20% reduction in heart rate from the baseline occurs. Haemodynamic measurements will be
      repeated to assess the acute response to beta-adrenoreceptor blocker agent. The change in the
      HWF will be recorded post beta-adrenoreceptor blocker administration. This study will be a
      validation and interventional study. It is an open labeled study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of Correlation of HWF as detected on doppler ultrasound (tri-, bi,- monophasic pattern) and HVPG (mm Hg) as assessed at hepatic vein catherization in the portal hypertensive patient .
time frame: 6 hours
arm group label: Single
arm group type: Experimental
description: To administer Carvedilol 12.5 mg orally and measure Wedge pressure gradient in hepatic veins followed by change in hepatic vein wave form
intervention type: Drug
intervention name: Carvedilol
description: Single dose of oral carvedilol 12.5 mg and wait till the time there's 20% reduction in hepatic wedge pressure gradient from the baseline.
arm group label: Single
other name: carveda
criteria: 
gender: All
minimum age: 17 Years
maximum age: 70 Years
healthy volunteers: No
last name: Syed Hasnain A Shah, M.D.
phone: 00922134864676
email: hasnain.alishah@aku.edu
facility: 
status: Recruiting
contact: 
country: Pakistan
responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: Dr. Syed Hasnain Ali Shah
investigator title: Professor
mesh term: Hypertension, Portal
mesh term: Hypertension
mesh term: Carvedilol
sharing ipd: No