<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/NCT04463394</url>
  </required_header>
  <id_info>
    <org_study_id>56875</org_study_id>
    <nct_id>NCT04463394</nct_id>
  </id_info>
  <brief_title>The Hemodynamic Effects of Vasopressin in Patients With Fontan Physiology</brief_title>
  <official_title>The Hemodynamic Effects of Vasopressin in Patients With Fontan Physiology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to evaluate if vasopressin can elevate systemic arterial blood&#xD;
      pressures without having a significant effect on pulmonary arterial pressures. Because&#xD;
      patients who have undergone Fontan procedures rely on low pressures across the pulmonary&#xD;
      vascular bed to maintain cardiac output, vasoactive agents that concomitantly increase&#xD;
      systemic and pulmonary pressures may have a deleterious effect in this specific patient&#xD;
      population.&#xD;
&#xD;
      Hypothesis: In patients with Fontan physiology, vasopressin will increase systemic BP by 20%&#xD;
      above baseline, without increasing the transpulmonary gradient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with Fontan physiology are at increased risk of developing hypotension during&#xD;
      periods of illness or with anesthesia. These patients have changes in venous capacitance,&#xD;
      compliance, and venomotor tone. When hypotension occurs, the approach to management requires&#xD;
      a careful understanding of these changes and the selection of appropriate, efficacious&#xD;
      vasoactive agents. Vasoconstrictive medications are frequently used to treat hypotension when&#xD;
      patients are refractory to fluid resuscitation. However, most of these medications have an&#xD;
      effect on both the systemic and pulmonary circulations, raising the vascular pressures of&#xD;
      both circuits. However, these patients often do not tolerate abrupt increases in pulmonary&#xD;
      arterial pressures or vascular resistance, and a low transpulmonary gradient is imperative to&#xD;
      maintain cardiac output. The ideal agent would be one that raises systemic vascular pressure&#xD;
      while having a minimal effect on the pulmonary circulation.&#xD;
&#xD;
      One promising medication for treating hypotension in Fontan patients is vasopressin. One&#xD;
      prior study evaluated the hemodynamic effect of vasopressin in pediatric patients with&#xD;
      pulmonary hypertension. Compared to other vasopressor agents (phenylephrine, epinephrine),&#xD;
      vasopressin increased systemic blood pressure with the least effect on pulmonary artery&#xD;
      pressure. In a second study evaluating the use of vasopressin specifically for patients&#xD;
      undergoing cardiac surgery for the creation of a Fontan, those who were treated with&#xD;
      vasopressin as part of their postoperative management demonstrated lower transpulmonary&#xD;
      gradients than those treated with placebo. Other studies have evaluated the use of&#xD;
      vasopressin in Fontan patients for other clinical outcomes, such as decreasing postoperative&#xD;
      chest tube output. On the basis of these studies, as well as our clinical experience managing&#xD;
      these patients in the operating room, procedural suites, and in the intensive care unit, the&#xD;
      investigator believes that vasopressin is not only safe but may be the preferred agent for&#xD;
      this patient population.&#xD;
&#xD;
      Although vasopressin has been studied extensively in the context of sepsis, post&#xD;
      cardiopulmonary bypass, and other vasoplegic disease states, the use of vasopressin has not&#xD;
      yet been studied in the general population of patients who have Fontan physiology. The&#xD;
      investigator hopes to demonstrate the efficacy of vasopressin as a medication specifically&#xD;
      for these patients, as one that can elevate systemic blood pressure without compromising&#xD;
      cardiac output or having a deleterious effect on the pulmonary vasculature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 12, 2020</start_date>
  <completion_date type="Actual">February 15, 2022</completion_date>
  <primary_completion_date type="Actual">February 15, 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Using Minimal Sample size estimation based on the primary outcome (PVR/SVR ratio) based on paired means for decreases in PVR/SVR ratio after vasopressin administration from a prior study at our institution. We calculated a minimum sample size of 28 for a power of 0.8 and and 0.05 significant difference.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in systemic (aortic) blood pressure</measure>
    <time_frame>Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in pulmonary artery pressure</measure>
    <time_frame>Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in transpulmonary gradient</measure>
    <time_frame>Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)</time_frame>
    <description>Transpulmonary gradient = Mean pulmonary arterial pressure - left atrial pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PVR/SVR Ratio</measure>
    <time_frame>Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Hypotension</condition>
  <condition>Fontan Physiology</condition>
  <arm_group>
    <arm_group_label>Vasopressin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants undergoing cardiac catheterization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vasopressin</intervention_name>
    <description>Vasopressin administered intravenously</description>
    <arm_group_label>Vasopressin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. All patients scheduled for cardiac catheterization at Lucile Packard Children's Hospital&#xD;
        with Fontan circulation&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Critical illness severe enough to preclude extended cardiac catheterization time&#xD;
&#xD;
          2. Patients already on vasopressin&#xD;
&#xD;
          3. Patients with pulmonary hypertension.&#xD;
&#xD;
          4. Patient not scheduled for cardiac catheterization at Lucile Packard Children's&#xD;
             Hospital (LPCH).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manchula Navaratnam, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Siehr SL, Feinstein JA, Yang W, Peng LF, Ogawa MT, Ramamoorthy C. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study. Pediatr Crit Care Med. 2016 May;17(5):428-37. doi: 10.1097/PCC.0000000000000716.</citation>
    <PMID>27144689</PMID>
  </reference>
  <reference>
    <citation>Kumar TK, Kashyap P, Figueroa M, Zurakowski D, Allen J, Ballweg JA, Sathanandam S, Ali M, Knott-Craig CJ. Vasopressin After the Fontan Operation. World J Pediatr Congenit Heart Surg. 2016 Jan;7(1):43-8. doi: 10.1177/2150135115614574.</citation>
    <PMID>26714993</PMID>
  </reference>
  <reference>
    <citation>Bigelow AM, Ghanayem NS, Thompson NE, Scott JP, Cassidy LD, Woods KJ, Woods RK, Mitchell ME, Hraska V, Hoffman GM. Safety and Efficacy of Vasopressin After Fontan Completion: A Randomized Pilot Study. Ann Thorac Surg. 2019 Dec;108(6):1865-1874. doi: 10.1016/j.athoracsur.2019.06.053. Epub 2019 Aug 7.</citation>
    <PMID>31400337</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>April 14, 2023</last_update_submitted>
  <last_update_submitted_qc>April 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Manchula Navaratnam</investigator_full_name>
    <investigator_title>Clinical Associate Professor, Anesthesiology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vasopressins</mesh_term>
    <mesh_term>Arginine Vasopressin</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/NCT04463394
org study id: 56875
nct id: NCT04463394
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The goal of this study is to evaluate if vasopressin can elevate systemic arterial blood
      pressures without having a significant effect on pulmonary arterial pressures. Because
      patients who have undergone Fontan procedures rely on low pressures across the pulmonary
      vascular bed to maintain cardiac output, vasoactive agents that concomitantly increase
      systemic and pulmonary pressures may have a deleterious effect in this specific patient
      population.

      Hypothesis: In patients with Fontan physiology, vasopressin will increase systemic BP by 20%
      above baseline, without increasing the transpulmonary gradient.
Patients with Fontan physiology are at increased risk of developing hypotension during
      periods of illness or with anesthesia. These patients have changes in venous capacitance,
      compliance, and venomotor tone. When hypotension occurs, the approach to management requires
      a careful understanding of these changes and the selection of appropriate, efficacious
      vasoactive agents. Vasoconstrictive medications are frequently used to treat hypotension when
      patients are refractory to fluid resuscitation. However, most of these medications have an
      effect on both the systemic and pulmonary circulations, raising the vascular pressures of
      both circuits. However, these patients often do not tolerate abrupt increases in pulmonary
      arterial pressures or vascular resistance, and a low transpulmonary gradient is imperative to
      maintain cardiac output. The ideal agent would be one that raises systemic vascular pressure
      while having a minimal effect on the pulmonary circulation.

      One promising medication for treating hypotension in Fontan patients is vasopressin. One
      prior study evaluated the hemodynamic effect of vasopressin in pediatric patients with
      pulmonary hypertension. Compared to other vasopressor agents (phenylephrine, epinephrine),
      vasopressin increased systemic blood pressure with the least effect on pulmonary artery
      pressure. In a second study evaluating the use of vasopressin specifically for patients
      undergoing cardiac surgery for the creation of a Fontan, those who were treated with
      vasopressin as part of their postoperative management demonstrated lower transpulmonary
      gradients than those treated with placebo. Other studies have evaluated the use of
      vasopressin in Fontan patients for other clinical outcomes, such as decreasing postoperative
      chest tube output. On the basis of these studies, as well as our clinical experience managing
      these patients in the operating room, procedural suites, and in the intensive care unit, the
      investigator believes that vasopressin is not only safe but may be the preferred agent for
      this patient population.

      Although vasopressin has been studied extensively in the context of sepsis, post
      cardiopulmonary bypass, and other vasoplegic disease states, the use of vasopressin has not
      yet been studied in the general population of patients who have Fontan physiology. The
      investigator hopes to demonstrate the efficacy of vasopressin as a medication specifically
      for these patients, as one that can elevate systemic blood pressure without compromising
      cardiac output or having a deleterious effect on the pulmonary vasculature.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Using Minimal Sample size estimation based on the primary outcome (PVR/SVR ratio) based on paired means for decreases in PVR/SVR ratio after vasopressin administration from a prior study at our institution. We calculated a minimum sample size of 28 for a power of 0.8 and and 0.05 significant difference.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in systemic (aortic) blood pressure
time frame: Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
measure: Change in pulmonary artery pressure
time frame: Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
measure: Change in transpulmonary gradient
time frame: Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
description: Transpulmonary gradient = Mean pulmonary arterial pressure - left atrial pressure
measure: PVR/SVR Ratio
time frame: Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
arm group label: Vasopressin
arm group type: Experimental
description: Participants undergoing cardiac catheterization
intervention type: Drug
intervention name: Vasopressin
description: Vasopressin administered intravenously
arm group label: Vasopressin
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Manchula Navaratnam, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
facility: 
country: United States
citation: Siehr SL, Feinstein JA, Yang W, Peng LF, Ogawa MT, Ramamoorthy C. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study. Pediatr Crit Care Med. 2016 May;17(5):428-37. doi: 10.1097/PCC.0000000000000716.
PMID: 27144689
citation: Kumar TK, Kashyap P, Figueroa M, Zurakowski D, Allen J, Ballweg JA, Sathanandam S, Ali M, Knott-Craig CJ. Vasopressin After the Fontan Operation. World J Pediatr Congenit Heart Surg. 2016 Jan;7(1):43-8. doi: 10.1177/2150135115614574.
PMID: 26714993
citation: Bigelow AM, Ghanayem NS, Thompson NE, Scott JP, Cassidy LD, Woods KJ, Woods RK, Mitchell ME, Hraska V, Hoffman GM. Safety and Efficacy of Vasopressin After Fontan Completion: A Randomized Pilot Study. Ann Thorac Surg. 2019 Dec;108(6):1865-1874. doi: 10.1016/j.athoracsur.2019.06.053. Epub 2019 Aug 7.
PMID: 31400337
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Manchula Navaratnam
investigator title: Clinical Associate Professor, Anesthesiology
mesh term: Hypotension
mesh term: Vasopressins
mesh term: Arginine Vasopressin
sharing ipd: No