<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/NCT04474262</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-ACLF-06</org_study_id>
    <nct_id>NCT04474262</nct_id>
  </id_info>
  <brief_title>Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients.</brief_title>
  <official_title>Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients-A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</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>
      The patients with ACLF having Ascites who require ascitic tapping will undergone ascitic&#xD;
      tapeither under albumin cover alone or with midodrine. The patient will be monitored for&#xD;
      complication and changes of PICD. Study analysis will be done with primary objective being&#xD;
      reduction in incidence of PICD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVE:&#xD;
&#xD;
      Primary objective: Incidence of Paracentesis induced circulatory dysfunction in patients&#xD;
      undergoing modest volume paracentesis (MVP) (&gt;3 and &lt;5 litres) with midodrine plus 25%&#xD;
      albumin v/s 25% albumin infusion alone at day 7&#xD;
&#xD;
      Secondary objective:&#xD;
&#xD;
        -  Change in systolic, diastolic and mean BP at day 3 and 6&#xD;
&#xD;
        -  Increase in plasma renin activity at day 6&#xD;
&#xD;
        -  Incidence of Hyponatremia, HE and AKI at day 3 and 6&#xD;
&#xD;
        -  Predictors of Paracentesis induced circulatory dysfunction&#xD;
&#xD;
        -  Predictors of 28 day survival.&#xD;
&#xD;
      Methodology :&#xD;
&#xD;
      Patients with Acute on chronic liver failure having grade III ascites will be given either&#xD;
      albumin or albumin plus midodrine. Midodrine will be started 4 hrs before tap to achieve&#xD;
      target MAP. Ascitic tapping will be followed by vital monitoring and monitoring of vital&#xD;
      parameters along with measurement of changes in s. rennin at day 3 and 6.&#xD;
&#xD;
        -  All patient will be undergo complete physical examination and complete clinical history&#xD;
           will be recorded.&#xD;
&#xD;
        -  Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin&#xD;
           levels&#xD;
&#xD;
        -  Those eligible will be randomised in to two groups&#xD;
&#xD;
        -  GROUP A will be given albumin 8g/l of ascitic tap during tap along with placebo for 7&#xD;
           days.&#xD;
&#xD;
        -  GROUP B will be given midodrine 7.5 mg to 12.5 mg tds (keeping the target MAP above 70&#xD;
           mmhg)for 7 days plus albumin same as in other group.&#xD;
&#xD;
      Study Population: Patients of acute on chronic liver failure who are admitted to and&#xD;
      attending the OPD at ILBS.&#xD;
&#xD;
      Study Design: Randomized controlled trial Study Period:NOV 2019 to march 2019&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      Considering incidence of PICD in albumin group is 30% and reduction to 10% by adding&#xD;
      midodrine with alpha =5%, and power of study being 80%. No. of cases in each group- 66&#xD;
      Total-132 Furthur with 10% dropout we need to enroll 150 cases (75 in each group) randomly&#xD;
      allocated in two groups by block randomization method with block size of 5.&#xD;
&#xD;
        -  Intervention: This RCT will be conducted at ILBS New Delhi between Dec 2019 and March&#xD;
           2021&#xD;
&#xD;
        -  Monitoring and assessment:&#xD;
&#xD;
        -  All patient will be undergo complete physical examination and complete clinical history&#xD;
           will be recorded.&#xD;
&#xD;
        -  Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin&#xD;
           levels&#xD;
&#xD;
        -  Those eligible will be randomised in to two groups&#xD;
&#xD;
        -  GROUP A will be given albumin 8g/l of ascitic tap along with placebo for 7 days.&#xD;
           Standard albumin therapy will continue (40gm/week)&#xD;
&#xD;
        -  GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70&#xD;
           mmhg)for 7 days plus albumin same as in other group.&#xD;
&#xD;
      Expected outcome of the project:&#xD;
&#xD;
      Primary:&#xD;
&#xD;
        -  Incidence of PICD at day 3 and day6&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  Changes in hemodynamic parameters at 1, 3 and 6 hour, Day 3, Day 6 post paracentesis&#xD;
&#xD;
        -  Increase in plasma renin activity at Day 3, Day 6&#xD;
&#xD;
        -  Incidence of Hyponatremia, HE and AKI at day 3 and 6&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 15, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2021</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 (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)</measure>
    <time_frame>Day 3</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)</measure>
    <time_frame>Day 6</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Mean Arterial Pressure (MAP) post paracentesis.</measure>
    <time_frame>1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Heart Rate post paracentesis.</measure>
    <time_frame>1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mean Arterial Pressure (MAP) post paracentesis.</measure>
    <time_frame>3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Heart Rate post paracentesis.</measure>
    <time_frame>3 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mean Arterial Pressure (MAP) post paracentesis.</measure>
    <time_frame>6 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Heart Rate post paracentesis.</measure>
    <time_frame>6 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mean Arterial Pressure (MAP) post paracentesis.</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Heart Rate post paracentesis.</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mean Arterial Pressure (MAP) post paracentesis.</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Heart Rate post paracentesis.</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma renin activity in both groups</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma renin activity in both groups</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Hyponatremia in both groups</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Hyponatremia in both groups</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Hepatic Encephalopathy in both groups</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Hepatic Encephalopathy in both groups</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Acute Kidney Injury in both groups</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Acute Kidney Injury in both groups</measure>
    <time_frame>Day 6</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Acute-On-Chronic Liver Failure</condition>
  <arm_group>
    <arm_group_label>Albumin with placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Albumin with Midodrine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Albumin</intervention_name>
    <description>Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week)</description>
    <arm_group_label>Albumin with Midodrine</arm_group_label>
    <arm_group_label>Albumin with placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midodrine Oral Tablet</intervention_name>
    <description>Midodrine 7.5 mg to 10 mg TDS (keeping the target MAP above 70 mmHg).</description>
    <arm_group_label>Albumin with Midodrine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Albumin with placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - ACLF patients (as per APASL definition) with grade II/III ascites&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 or &gt;75 years&#xD;
&#xD;
          2. Hepatocellular carcinoma&#xD;
&#xD;
          3. Extrahepatic portal vein obstruction&#xD;
&#xD;
          4. Non cirrhotic ascites&#xD;
&#xD;
          5. Serum creatinine &gt;1.5mg/dl&#xD;
&#xD;
          6. Refractory septic shock&#xD;
&#xD;
          7. Beta blockersPortal vein thrombosis&#xD;
&#xD;
          8. Grade 3-4 HE&#xD;
&#xD;
          9. Pregnancy or Lactation&#xD;
&#xD;
         10. Active variceal bleed&#xD;
&#xD;
         11. Respiratory, cardiac, renal failure&#xD;
&#xD;
         12. Uncontrolled hypertension&#xD;
&#xD;
         13. Severe coagulopathy&#xD;
&#xD;
         14. Refusal to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dr Ajay Mishra, MD</last_name>
    <phone>01146300000</phone>
    <email>ajaymishrapandit@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
    <contact>
      <last_name>Dr Ajay Mishra, MD</last_name>
      <phone>01146300000</phone>
      <email>ajaymishrapandit@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>July 13, 2020</last_update_submitted>
  <last_update_submitted_qc>July 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2020</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>Liver Failure</mesh_term>
    <mesh_term>End Stage Liver Disease</mesh_term>
    <mesh_term>Acute-On-Chronic Liver Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midodrine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04474262
org study id: ILBS-ACLF-06
nct id: NCT04474262
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The patients with ACLF having Ascites who require ascitic tapping will undergone ascitic
      tapeither under albumin cover alone or with midodrine. The patient will be monitored for
      complication and changes of PICD. Study analysis will be done with primary objective being
      reduction in incidence of PICD.
OBJECTIVE:

      Primary objective: Incidence of Paracentesis induced circulatory dysfunction in patients
      undergoing modest volume paracentesis (MVP) (>3 and <5 litres) with midodrine plus 25%
      albumin v/s 25% albumin infusion alone at day 7

      Secondary objective:

        -  Change in systolic, diastolic and mean BP at day 3 and 6

        -  Increase in plasma renin activity at day 6

        -  Incidence of Hyponatremia, HE and AKI at day 3 and 6

        -  Predictors of Paracentesis induced circulatory dysfunction

        -  Predictors of 28 day survival.

      Methodology :

      Patients with Acute on chronic liver failure having grade III ascites will be given either
      albumin or albumin plus midodrine. Midodrine will be started 4 hrs before tap to achieve
      target MAP. Ascitic tapping will be followed by vital monitoring and monitoring of vital
      parameters along with measurement of changes in s. rennin at day 3 and 6.

        -  All patient will be undergo complete physical examination and complete clinical history
           will be recorded.

        -  Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin
           levels

        -  Those eligible will be randomised in to two groups

        -  GROUP A will be given albumin 8g/l of ascitic tap during tap along with placebo for 7
           days.

        -  GROUP B will be given midodrine 7.5 mg to 12.5 mg tds (keeping the target MAP above 70
           mmhg)for 7 days plus albumin same as in other group.

      Study Population: Patients of acute on chronic liver failure who are admitted to and
      attending the OPD at ILBS.

      Study Design: Randomized controlled trial Study Period:NOV 2019 to march 2019

      Sample Size:

      Considering incidence of PICD in albumin group is 30% and reduction to 10% by adding
      midodrine with alpha =5%, and power of study being 80%. No. of cases in each group- 66
      Total-132 Furthur with 10% dropout we need to enroll 150 cases (75 in each group) randomly
      allocated in two groups by block randomization method with block size of 5.

        -  Intervention: This RCT will be conducted at ILBS New Delhi between Dec 2019 and March
           2021

        -  Monitoring and assessment:

        -  All patient will be undergo complete physical examination and complete clinical history
           will be recorded.

        -  Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin
           levels

        -  Those eligible will be randomised in to two groups

        -  GROUP A will be given albumin 8g/l of ascitic tap along with placebo for 7 days.
           Standard albumin therapy will continue (40gm/week)

        -  GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70
           mmhg)for 7 days plus albumin same as in other group.

      Expected outcome of the project:

      Primary:

        -  Incidence of PICD at day 3 and day6

      Secondary:

        -  Changes in hemodynamic parameters at 1, 3 and 6 hour, Day 3, Day 6 post paracentesis

        -  Increase in plasma renin activity at Day 3, Day 6

        -  Incidence of Hyponatremia, HE and AKI at day 3 and 6
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)
time frame: Day 3
measure: Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)
time frame: Day 6
measure: Changes in Mean Arterial Pressure (MAP) post paracentesis.
time frame: 1 hour
measure: Changes in Heart Rate post paracentesis.
time frame: 1 hour
measure: Changes in Mean Arterial Pressure (MAP) post paracentesis.
time frame: 3 hours
measure: Changes in Heart Rate post paracentesis.
time frame: 3 hours
measure: Changes in Mean Arterial Pressure (MAP) post paracentesis.
time frame: 6 hours
measure: Changes in Heart Rate post paracentesis.
time frame: 6 hours
measure: Changes in Mean Arterial Pressure (MAP) post paracentesis.
time frame: Day 3
measure: Changes in Heart Rate post paracentesis.
time frame: Day 3
measure: Changes in Mean Arterial Pressure (MAP) post paracentesis.
time frame: Day 6
measure: Changes in Heart Rate post paracentesis.
time frame: Day 6
measure: Change in plasma renin activity in both groups
time frame: Day 3
measure: Change in plasma renin activity in both groups
time frame: Day 6
measure: Incidence of Hyponatremia in both groups
time frame: Day 3
measure: Incidence of Hyponatremia in both groups
time frame: Day 6
measure: Incidence of Hepatic Encephalopathy in both groups
time frame: Day 3
measure: Incidence of Hepatic Encephalopathy in both groups
time frame: Day 6
measure: Incidence of Acute Kidney Injury in both groups
time frame: Day 3
measure: Incidence of Acute Kidney Injury in both groups
time frame: Day 6
arm group label: Albumin with placebo
arm group type: Active Comparator
description: Group A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week)
arm group label: Albumin with Midodrine
arm group type: Experimental
description: GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group.
intervention type: Biological
intervention name: Albumin
description: Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week)
arm group label: Albumin with Midodrine
arm group label: Albumin with placebo
intervention type: Drug
intervention name: Midodrine Oral Tablet
description: Midodrine 7.5 mg to 10 mg TDS (keeping the target MAP above 70 mmHg).
arm group label: Albumin with Midodrine
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Albumin with placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dr Ajay Mishra, MD
phone: 01146300000
email: ajaymishrapandit@gmail.com
facility: 
contact: 
country: India
responsible party type: Sponsor
mesh term: Liver Failure
mesh term: End Stage Liver Disease
mesh term: Acute-On-Chronic Liver Failure
mesh term: Midodrine
sharing ipd: Undecided