<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/NCT03279861</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00076889</org_study_id>
    <nct_id>NCT03279861</nct_id>
  </id_info>
  <brief_title>Sacubitril-valsartan Versus Usual Anti-hypertensives in LVAD</brief_title>
  <official_title>Sacubitril-valsartan (Entresto) Versus Standard Anti-hypertensive Therapy in LVAD Patients - A Feasibility Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medtronic</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Maryland, Baltimore</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>
      This pilot, feasibility study evaluates the efficacy of sacubitril-valsartan (Entresto)&#xD;
      versus usual anti-hypertensive medications in patients with left ventricular assist devices&#xD;
      (LVAD). It also measures diurnal blood pressure variations in the context of continuous flow&#xD;
      physiology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Left ventricular assist devices (LVAD) have become a life-saving therapy for patients with&#xD;
      ACC/AHA stage D congestive heart failure (CHF). Despite longevity and improved quality of&#xD;
      life, LVAD-supported patients are plagued with adverse events, the most debilitating of all&#xD;
      is stroke. Ischemic and hemorrhagic strokes have been associated with hypertension (mean&#xD;
      arterial pressure, or MAP &gt; 90 mmHg) in addition to out-of-range INR and aspirin doses.&#xD;
      Strict blood pressure control has been shown in a recent randomized trial to confer a&#xD;
      significant decline in stroke rates of patients implanted with the Heartware LVAD. Patients&#xD;
      with poorly controlled hypertension are also at risk for inadequate left-ventricular&#xD;
      unloading and worsening CHF due to the exquisite sensitivity to afterload of the continuous&#xD;
      flow LVAD.&#xD;
&#xD;
      There are no guidelines for the use of anti-hypertensives in LVAD patients. Most are started&#xD;
      on standard CHF therapies, though this practice varies greatly across LVAD centers. The&#xD;
      angiotensin receptor blocker-neprilysin inhibitor sacubitril-valsartan (Entresto) is a potent&#xD;
      anti-hypertensive mediation that was recently approved by the Food and Drug Administration&#xD;
      for the treatment of patients with heart failure and low ejection fraction. We aim to&#xD;
      randomly assign patients to receive Entresto or usual anti-hypertensive therapy for blood&#xD;
      pressure control, then crossover to the other arm after 30 days. Daily blood pressure&#xD;
      measurements will be performed and correlated with LVAD pump flows and waveform analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    protocol change&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2017</start_date>
  <completion_date type="Anticipated">November 2019</completion_date>
  <primary_completion_date type="Anticipated">November 2018</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time spent with MAP &lt; 85 mmHg</measure>
    <time_frame>2 months</time_frame>
    <description>Daily mean arterial pressure (MAP) &lt; 85 mmHg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of drugs</measure>
    <time_frame>2 months</time_frame>
    <description>Number of anti-hypertensive drugs needed to achieve MAP &lt; 85 mmHg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pump flow</measure>
    <time_frame>2 months</time_frame>
    <description>Correlation of pump flow with daily MAP</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Congestive Heart Failure</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Entresto</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>First-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual meds</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>First-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entresto</intervention_name>
    <description>First line therapy in Entresto arm</description>
    <arm_group_label>Entresto</arm_group_label>
    <arm_group_label>Usual meds</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valsartan</intervention_name>
    <description>First line therapy in &quot;usual meds&quot; arm</description>
    <arm_group_label>Entresto</arm_group_label>
    <arm_group_label>Usual meds</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  More than 30 days after LVAD implant&#xD;
&#xD;
          -  Ambulatory&#xD;
&#xD;
          -  MAP &gt; 85 mmHg requiring initiation of anti-hypertensive medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to ACEI or ARB&#xD;
&#xD;
          -  eGFR &lt; 30 mL/min/1.73m2&#xD;
&#xD;
          -  K &gt; 5.4 mmol/L&#xD;
&#xD;
          -  MAP &lt; 60&#xD;
&#xD;
          -  Inability to check blood pressure at home&#xD;
&#xD;
          -  Lack of prescription coverage&#xD;
&#xD;
          -  Frequent hospitalizations (monthly)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Van-Khue Ton, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland</affiliation>
  </overall_official>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 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>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</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/NCT03279861
org study id: HP-00076889
nct id: NCT03279861
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This pilot, feasibility study evaluates the efficacy of sacubitril-valsartan (Entresto)
      versus usual anti-hypertensive medications in patients with left ventricular assist devices
      (LVAD). It also measures diurnal blood pressure variations in the context of continuous flow
      physiology.
Left ventricular assist devices (LVAD) have become a life-saving therapy for patients with
      ACC/AHA stage D congestive heart failure (CHF). Despite longevity and improved quality of
      life, LVAD-supported patients are plagued with adverse events, the most debilitating of all
      is stroke. Ischemic and hemorrhagic strokes have been associated with hypertension (mean
      arterial pressure, or MAP > 90 mmHg) in addition to out-of-range INR and aspirin doses.
      Strict blood pressure control has been shown in a recent randomized trial to confer a
      significant decline in stroke rates of patients implanted with the Heartware LVAD. Patients
      with poorly controlled hypertension are also at risk for inadequate left-ventricular
      unloading and worsening CHF due to the exquisite sensitivity to afterload of the continuous
      flow LVAD.

      There are no guidelines for the use of anti-hypertensives in LVAD patients. Most are started
      on standard CHF therapies, though this practice varies greatly across LVAD centers. The
      angiotensin receptor blocker-neprilysin inhibitor sacubitril-valsartan (Entresto) is a potent
      anti-hypertensive mediation that was recently approved by the Food and Drug Administration
      for the treatment of patients with heart failure and low ejection fraction. We aim to
      randomly assign patients to receive Entresto or usual anti-hypertensive therapy for blood
      pressure control, then crossover to the other arm after 30 days. Daily blood pressure
      measurements will be performed and correlated with LVAD pump flows and waveform analysis.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time spent with MAP < 85 mmHg
time frame: 2 months
description: Daily mean arterial pressure (MAP) < 85 mmHg
measure: Number of drugs
time frame: 2 months
description: Number of anti-hypertensive drugs needed to achieve MAP < 85 mmHg
measure: Pump flow
time frame: 2 months
description: Correlation of pump flow with daily MAP
arm group label: Entresto
arm group type: Active Comparator
description: First-line anti-hypertensive: sacubitril-valsartan, starting at 24-26 mg twice daily, increasing to maximum dose of 97-103 mg twice daily
arm group label: Usual meds
arm group type: Active Comparator
description: First-line anti-hypertensive: valsartan, starting at 40 mg twice daily, increasing to a maximum dose of 160 mg twice daily
intervention type: Drug
intervention name: Entresto
description: First line therapy in Entresto arm
arm group label: Entresto
arm group label: Usual meds
intervention type: Drug
intervention name: Valsartan
description: First line therapy in "usual meds" arm
arm group label: Entresto
arm group label: Usual meds
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Van-Khue Ton, MD PhD
role: Principal Investigator
affiliation: University of Maryland
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Valsartan
mesh term: Sacubitril and valsartan sodium hydrate drug combination
sharing ipd: No