<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/NCT04460560</url>
  </required_header>
  <id_info>
    <org_study_id>834744</org_study_id>
    <nct_id>NCT04460560</nct_id>
  </id_info>
  <brief_title>Terlipressin for HRS-AKI in Liver Transplant Candidates (INFUSE)</brief_title>
  <acronym>INFUSE</acronym>
  <official_title>A Multi-Center, Open Label, Collaborative Research Study to Treat HRS-AKI Patients With Continuous Terlipressin Infusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hepatorenal syndrome-acute kidney injury (HRS-AKI), a potentially reversible renal failure,&#xD;
      is a serious, rapidly progressing, often fatal, complication of decompensated cirrhosis.&#xD;
      Terlipressin is a synthetic vasopressin analogue that acts as a systemic vasoconstrictor via&#xD;
      the vascular vasopressin V1 receptors. In HRS-AKI patients the strong V1 receptor-mediated&#xD;
      vasoconstrictor activity of terlipressin, particularly in the splanchnic area, increases&#xD;
      effective intravascular volume and mean arterial pressure (MAP), ameliorates&#xD;
      renin-angiotensin-aldosterone system and sympathetic nervous system hyperactivity, and&#xD;
      improves renal blood flow. The INFUSE trial will evaluate the use of continuous terlipressin&#xD;
      infusion in patients on the liver transplant waiting list with HRS-AKI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 11, 2020</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of renal function (SCr) from Day 1 thru end of treatment, repeated measure analysis. SCr will be collected daily, from Day 1 thru end of treatment. Baseline SCr will also be entered.</measure>
    <time_frame>14 days or reversal of HRS-AKI, whichever occur first</time_frame>
    <description>SCr will be collected daily, from Day 1 thru end of treatment.</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Hepatorenal Syndrome</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Terlipressin</intervention_name>
    <description>For the first dose of terlipressin, each vial will be reconstituted with 5 mL of sterile 0.9% sodium chloride solution and administered intravenously as a bolus injection and given over 1 minute at a dose of 0.5 mg.&#xD;
For continuous infusion, the dose of terlipressin is to be dissolved in 0.9% sodium chloride solution and infused with a pump</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent by subject or legally authorized representative.&#xD;
&#xD;
          2. At least 18 years of age.&#xD;
&#xD;
          3. Cirrhosis and ascites.&#xD;
&#xD;
          4. No sustained improvement in renal function (less than 20% decrease in SCr) at least 48&#xD;
             hours after diuretic withdrawal and after plasma volume expansion with albumin (given&#xD;
             daily for two days - 48 hours minimum from 1st dose). If SCr improves by ≥ 20 % but&#xD;
             plateaus ( ≤ 10 % fluctuation in sCr) and remains above 1.5 mg/dl for ≥another 48 hrs&#xD;
             and there are no features of acute tubular necrosis.&#xD;
&#xD;
          5. Increase in SCr by at least ≥ 0.3 mg/dl OR 1.5-2 fold above baseline (AKI stage 1 and&#xD;
             above), to a SCr of ≥ 1.5 mg/dl at the time of initiating treatment. Baseline SCr is&#xD;
             defined as the most recent, lowest SCr within last 6 months before date of current&#xD;
             admission.&#xD;
&#xD;
          6. A.On liver transplant wait list or liver transplant eligible with anticipation of&#xD;
             being placed on the liver transplant wait list. B. Patients not on the transplant&#xD;
             waitlist or transplant eligible are also eligible for the trial ( maximum 25 subjects)&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serum creatinine level greater than 5.0 mg/dL. Subjects with value greater than 5.0&#xD;
             mg/dL may be enrolled with Sponsor prior approval.&#xD;
&#xD;
          2. MELD score ≥ 35&#xD;
&#xD;
          3. Acute on Chronic Liver Failure (ACLF) grade 3 (according to the CLIF Consortium&#xD;
             grading system).&#xD;
&#xD;
          4. Uncontrolled sepsis and/or uncontrolled bacterial infection (e.g., persisting&#xD;
             bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with&#xD;
             vasomotor instability).&#xD;
&#xD;
          5. Shock.&#xD;
&#xD;
          6. Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents:&#xD;
             eg, aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal&#xD;
             anti-inflammatory drugs (NSAIDs: e.g., ibuprofen, naproxen, diclofenac), significant&#xD;
             exposure to radiographic contrast agents (large doses or multiple injections of&#xD;
             iodinated contrast media; e.g., during coronary or abdominal angiogram).&#xD;
&#xD;
          7. Estimated life expectancy of less than 7 days.&#xD;
&#xD;
          8. Advanced Hepatocellular Carcinoma ( HCC) with expected survival of &lt; 6 months&#xD;
&#xD;
          9. Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary&#xD;
             supplements, herbal preparations, viral hepatitis, or toxins (e.g., Amanita toxin with&#xD;
             mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic&#xD;
             hepatitis.&#xD;
&#xD;
         10. Evidence of obstructive uropathy or parenchymal renal disease. Renal ultrasound or&#xD;
             other imaging not required but should be taken if suspicious.&#xD;
&#xD;
         11. Tubular epithelial casts, heme granular casts (range of 1-3 granular casts&#xD;
             acceptable), hematuria or microhematuria on urinalysis that is indicative of acute&#xD;
             tubular necrosis and/or intrinsic renal disease.&#xD;
&#xD;
         12. Subjects known to be pregnant; all women of child-bearing age and potential must have&#xD;
             a negative pregnancy test.&#xD;
&#xD;
         13. Severe cardiovascular disease, including, but not limited to, unstable angina,&#xD;
             pulmonary edema, congestive heart failure, or persisting symptomatic peripheral&#xD;
             vascular disease, myocardial infarction or stable chronic angina within the past 12&#xD;
             months, or any other cardiovascular disease judged by the investigator to be severe&#xD;
             and creates a risk to subject with concurrent terlipressin use.&#xD;
&#xD;
         14. Current or recent (within 4 weeks) renal replacement therapy (RRT) or anticipation of&#xD;
             RRT within 3 days on enrollment.&#xD;
&#xD;
         15. Participation in other clinical research involving investigational medicinal products&#xD;
             within 30 days of starting study drug that would adversely affect participation in&#xD;
             this or the current trial.&#xD;
&#xD;
         16. Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of starting study&#xD;
             drug.&#xD;
&#xD;
         17. For the Prospective Group: All vasopressors must be stopped prior to treatment with&#xD;
             terlipressin. Use of vasopressors (e.g., norepinephrine, epinephrine or vasopressin&#xD;
             dopamine or other vasopressors) of ≥ 3 consecutive days within the prior 14-day&#xD;
             screening period are excluded. Patients receiving a vasopressor other than midodrine&#xD;
             within 24 hours of qualifying SCr are excluded, i.e, a 24-h washout is required prior&#xD;
             to enrollment.&#xD;
&#xD;
             Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and&#xD;
             octreotide treatment must be stopped prior to enrollment.&#xD;
&#xD;
         18. Known allergy or sensitivity to terlipressin.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Healthcare, Inc</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White All Saints Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 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>Hepatorenal Syndrome</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>


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/NCT04460560
org study id: 834744
nct id: NCT04460560
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Hepatorenal syndrome-acute kidney injury (HRS-AKI), a potentially reversible renal failure,
      is a serious, rapidly progressing, often fatal, complication of decompensated cirrhosis.
      Terlipressin is a synthetic vasopressin analogue that acts as a systemic vasoconstrictor via
      the vascular vasopressin V1 receptors. In HRS-AKI patients the strong V1 receptor-mediated
      vasoconstrictor activity of terlipressin, particularly in the splanchnic area, increases
      effective intravascular volume and mean arterial pressure (MAP), ameliorates
      renin-angiotensin-aldosterone system and sympathetic nervous system hyperactivity, and
      improves renal blood flow. The INFUSE trial will evaluate the use of continuous terlipressin
      infusion in patients on the liver transplant waiting list with HRS-AKI.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Improvement of renal function (SCr) from Day 1 thru end of treatment, repeated measure analysis. SCr will be collected daily, from Day 1 thru end of treatment. Baseline SCr will also be entered.
time frame: 14 days or reversal of HRS-AKI, whichever occur first
description: SCr will be collected daily, from Day 1 thru end of treatment.
intervention type: Drug
intervention name: Terlipressin
description: For the first dose of terlipressin, each vial will be reconstituted with 5 mL of sterile 0.9% sodium chloride solution and administered intravenously as a bolus injection and given over 1 minute at a dose of 0.5 mg.
For continuous infusion, the dose of terlipressin is to be dissolved in 0.9% sodium chloride solution and infused with a pump
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hepatorenal Syndrome
mesh term: Terlipressin
sharing ipd: No