<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/NCT04489589</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00096716</org_study_id>
    <nct_id>NCT04489589</nct_id>
  </id_info>
  <brief_title>Midodrine for the Early Liberation of Vasopressor Support in the ICU</brief_title>
  <acronym>LIBERATE</acronym>
  <official_title>Midodrine for the Early Liberation of Vasopressor Support in the ICU - The LIBERATE Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alberta Health services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute of Health Economics, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alberta</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vasopressors are medications that are given intravenously to increase the blood pressure of&#xD;
      patients with illnesses that cause dangerous blood pressure drops. When a doctor prescribes a&#xD;
      vasopressor, they ask that the dose be adjusted to achieve a specific blood pressure. This&#xD;
      kind of medical support with intravenous (IV) vasopressors are usual treatments in intensive&#xD;
      care unit (ICU) settings. Oral vasopressors, such as midodrine, have been historically used&#xD;
      to maintain blood pressure in non-critically ill patients. In this study, the investigators&#xD;
      will be using midodrine to reduce the need for IV vasopressors as blood pressure improves&#xD;
      during the stay in the ICU&#xD;
&#xD;
      The LIBERATE pilot study will evaluate the role of midodrine for patients with low blood&#xD;
      pressure in the ICU. The investigators are planning on enrolling up to 20 study participants&#xD;
      to evaluate this question in the General Systems ICU at the University of Alberta Hospital.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose: Resuscitation and hemodynamic support with intravenous (IV) vasopressors is a prime&#xD;
      indication of treatment in intensive care unit (ICU) settings. Hemodynamic support is&#xD;
      typically provided with intravenous (IV) vasopressors. However, these have been shown to have&#xD;
      significant negative effects including increased central venous catheter line associated&#xD;
      infections, venous thromboembolic disease, impaired mobility and gastrointestinal injury and&#xD;
      ischemia. Oral vasopressors, such as midodrine, have been historically used for hemodynamic&#xD;
      support in non-critically ill patients, but their study in patients as IV pressor sparing&#xD;
      therapy has been limited.&#xD;
&#xD;
      Hypothesis: to evaluate the expanded role of midodrine for any vasoplegic patients in the&#xD;
      ICU.&#xD;
&#xD;
      Justification: In 2018, there were 1,613 admissions to the adult general systems ICU (GSICU)&#xD;
      at the University of Alberta Hospital (UAH). Patients were sick, with a mean Acute Physiology&#xD;
      and Chronic Health Evaluation II (APACHE) score of 21.3, with 36.4% requiring vasopressors on&#xD;
      admission, accounting for 1942 patient-days (data from eCritical TRACER database). In the&#xD;
      environment strained healthcare resources and limited ICU capacity, the ability to safely&#xD;
      wean patients from IV vasopressors with transition to oral hemodynamic supporting agents&#xD;
      would greatly improve how patients navigate through the healthcare system. This in turn will&#xD;
      improve patient-centered case.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      To determine if recruitment for LIBERATE is achievable and feasible To compare the effect of&#xD;
      enteral midodrine vs placebo on duration of vasopressor support&#xD;
&#xD;
      Secondary Objective: To compare the effect of enteral midodrine vs. placebo on:&#xD;
&#xD;
      ICU length of stay 90-day all-cause mortality Rate of re-initiation of IV vasopressors Rates&#xD;
      of ICU re-admission Adverse events Research Method/Procedures: The LIBERATE Trial is a single&#xD;
      centre, concealed-allocation parallel-group blinded pilot RCT. Patients will be randomly&#xD;
      assigned to midodrine (enteral, 10mg every 8h) or placebo (microcrystalline cellulose) for&#xD;
      the duration of their IV vasopressor therapy and 24h following the discontinuation of their&#xD;
      IV vasopressor therapy. The recruitment target is 60 patients (i.e., 30 patients per arm)&#xD;
      with full follow-up to ensure feasibility. Study personnel at the clinical sites will&#xD;
      document the ICU length of stay. Daily assessment will occur for re-initiation of IV&#xD;
      vasopressors and ICU re-admission. Patients will be followed at 90 days for mortality.&#xD;
&#xD;
      Plan for Data Analysis: Analyses of the primary and secondary outcomes will involve summary&#xD;
      measures obtained by aggregating the endpoints using Stata software package (StataCorp,&#xD;
      Texas, USA). Baseline comparisons will be performed using chi-squared test for equal&#xD;
      proportions with results to be reported as numbers, percentages, and 95% confidence&#xD;
      intervals. Continuous normally distributed variables will be compared using paired t-tests&#xD;
      and reported as means with 95% confidence intervals, while non-normally distributed will be&#xD;
      compared using Wilcoxon rank sum tests and reported as medians and interquartile ranges.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 22, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <phase>Phase 4</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>Recruitment Rates</measure>
    <time_frame>1 year</time_frame>
    <description>Recruitment metrics by patients recruitment and consent rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of vasopressor support</measure>
    <time_frame>1 year</time_frame>
    <description>Duration of intravenous vasopressor support</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>1 year</time_frame>
    <description>Total duration of patient stay in ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Up to 90 days</time_frame>
    <description>All cause patient mortality within 90 days of study recruitment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-initiation of IV vasopressors</measure>
    <time_frame>1 year</time_frame>
    <description>Rate of re-initiation of intravenous vasopressors during ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU re-admissions</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of ICU re-admissions during same hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of adverse events during ICU stay</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Critical Illness</condition>
  <condition>Shock</condition>
  <arm_group>
    <arm_group_label>Midodrine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Midodrine 10mg PO/NG q8h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Microcrystalline cellulose PO/NG q8h</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midodrine</intervention_name>
    <description>10mg PO/NG q8h</description>
    <arm_group_label>Midodrine</arm_group_label>
    <other_name>Midodrine Hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>10mg PO/NG q8h</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Microcrystalline cellulose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
          -  ICU admission&#xD;
&#xD;
          -  Ongoing vasopressor support&#xD;
&#xD;
          -  Decreasing vasopressor dose&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Greater than 24 hours from peak vasopressor dose&#xD;
&#xD;
          -  Contraindication to enteral medications&#xD;
&#xD;
          -  Previously on midodrine in last 7 days&#xD;
&#xD;
          -  Expected death or withdrawal of life-sustaining therapies&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Known allergy to Midodrine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oleksa G Rewa, MD MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T5R0T1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>September 23, 2022</last_update_submitted>
  <last_update_submitted_qc>September 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</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>Critical Illness</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>No</sharing_ipd>
    <ipd_description>As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.</ipd_description>
  </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/NCT04489589
org study id: Pro00096716
nct id: NCT04489589
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Vasopressors are medications that are given intravenously to increase the blood pressure of
      patients with illnesses that cause dangerous blood pressure drops. When a doctor prescribes a
      vasopressor, they ask that the dose be adjusted to achieve a specific blood pressure. This
      kind of medical support with intravenous (IV) vasopressors are usual treatments in intensive
      care unit (ICU) settings. Oral vasopressors, such as midodrine, have been historically used
      to maintain blood pressure in non-critically ill patients. In this study, the investigators
      will be using midodrine to reduce the need for IV vasopressors as blood pressure improves
      during the stay in the ICU

      The LIBERATE pilot study will evaluate the role of midodrine for patients with low blood
      pressure in the ICU. The investigators are planning on enrolling up to 20 study participants
      to evaluate this question in the General Systems ICU at the University of Alberta Hospital.
Purpose: Resuscitation and hemodynamic support with intravenous (IV) vasopressors is a prime
      indication of treatment in intensive care unit (ICU) settings. Hemodynamic support is
      typically provided with intravenous (IV) vasopressors. However, these have been shown to have
      significant negative effects including increased central venous catheter line associated
      infections, venous thromboembolic disease, impaired mobility and gastrointestinal injury and
      ischemia. Oral vasopressors, such as midodrine, have been historically used for hemodynamic
      support in non-critically ill patients, but their study in patients as IV pressor sparing
      therapy has been limited.

      Hypothesis: to evaluate the expanded role of midodrine for any vasoplegic patients in the
      ICU.

      Justification: In 2018, there were 1,613 admissions to the adult general systems ICU (GSICU)
      at the University of Alberta Hospital (UAH). Patients were sick, with a mean Acute Physiology
      and Chronic Health Evaluation II (APACHE) score of 21.3, with 36.4% requiring vasopressors on
      admission, accounting for 1942 patient-days (data from eCritical TRACER database). In the
      environment strained healthcare resources and limited ICU capacity, the ability to safely
      wean patients from IV vasopressors with transition to oral hemodynamic supporting agents
      would greatly improve how patients navigate through the healthcare system. This in turn will
      improve patient-centered case.

      Primary Objective:

      To determine if recruitment for LIBERATE is achievable and feasible To compare the effect of
      enteral midodrine vs placebo on duration of vasopressor support

      Secondary Objective: To compare the effect of enteral midodrine vs. placebo on:

      ICU length of stay 90-day all-cause mortality Rate of re-initiation of IV vasopressors Rates
      of ICU re-admission Adverse events Research Method/Procedures: The LIBERATE Trial is a single
      centre, concealed-allocation parallel-group blinded pilot RCT. Patients will be randomly
      assigned to midodrine (enteral, 10mg every 8h) or placebo (microcrystalline cellulose) for
      the duration of their IV vasopressor therapy and 24h following the discontinuation of their
      IV vasopressor therapy. The recruitment target is 60 patients (i.e., 30 patients per arm)
      with full follow-up to ensure feasibility. Study personnel at the clinical sites will
      document the ICU length of stay. Daily assessment will occur for re-initiation of IV
      vasopressors and ICU re-admission. Patients will be followed at 90 days for mortality.

      Plan for Data Analysis: Analyses of the primary and secondary outcomes will involve summary
      measures obtained by aggregating the endpoints using Stata software package (StataCorp,
      Texas, USA). Baseline comparisons will be performed using chi-squared test for equal
      proportions with results to be reported as numbers, percentages, and 95% confidence
      intervals. Continuous normally distributed variables will be compared using paired t-tests
      and reported as means with 95% confidence intervals, while non-normally distributed will be
      compared using Wilcoxon rank sum tests and reported as medians and interquartile ranges.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Recruitment Rates
time frame: 1 year
description: Recruitment metrics by patients recruitment and consent rate
measure: Duration of vasopressor support
time frame: 1 year
description: Duration of intravenous vasopressor support
measure: ICU length of stay
time frame: 1 year
description: Total duration of patient stay in ICU
measure: Mortality
time frame: Up to 90 days
description: All cause patient mortality within 90 days of study recruitment
measure: Re-initiation of IV vasopressors
time frame: 1 year
description: Rate of re-initiation of intravenous vasopressors during ICU stay
measure: ICU re-admissions
time frame: 1 year
description: Rates of ICU re-admissions during same hospitalization
measure: Adverse events
time frame: 1 year
description: Rates of adverse events during ICU stay
arm group label: Midodrine
arm group type: Experimental
description: Midodrine 10mg PO/NG q8h
arm group label: Placebo
arm group type: Placebo Comparator
description: Microcrystalline cellulose PO/NG q8h
intervention type: Drug
intervention name: Midodrine
description: 10mg PO/NG q8h
arm group label: Midodrine
other name: Midodrine Hydrochloride
intervention type: Drug
intervention name: Placebo
description: 10mg PO/NG q8h
arm group label: Placebo
other name: Microcrystalline cellulose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oleksa G Rewa, MD MSc
role: Principal Investigator
affiliation: University of Alberta
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Critical Illness
mesh term: Midodrine
sharing ipd: No
ipd description: As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.