<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/NCT04458103</url>
  </required_header>
  <id_info>
    <org_study_id>2020P000422</org_study_id>
    <nct_id>NCT04458103</nct_id>
  </id_info>
  <brief_title>Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD</brief_title>
  <official_title>Percutaneous RVAD to Preemptively Treat Right Heart Failure Post-LVAD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prior studies have shown that left ventricular assist device (LVAD) implantation commonly&#xD;
      results in right ventricular failure (RVF). Right ventricular dysfunction and failure after&#xD;
      LVAD implantation is known to increase morbidity and mortality and contribute to longer&#xD;
      post-implant hospital length of stay. Since RVF is difficult to predict and can have harmful&#xD;
      effects such as increased ICU stay, adverse outcomes, and mortality, it could be beneficial&#xD;
      to preemptively treat patients through preoperative or intraoperative percutaneous right&#xD;
      ventricular assist device (RVAD) placement to prevent RVF.&#xD;
&#xD;
      This trial will include both a prospective interventional cohort and a retrospective control&#xD;
      cohort. The prospective interventional cohort will consist of patients undergoing LVAD&#xD;
      implantation at Massachusetts General Hospital. These patients will preemptively receive an&#xD;
      RVAD (either the ProtekDuo or Impella RP) surrounding LVAD implantation. The historical&#xD;
      control cohort will consist of retrospective data collection on patients who have undergone&#xD;
      LVAD implantation in the past. This group will be matched with the enrolled prospective&#xD;
      interventional patients. The purpose of this study is to compare clinical outcomes of&#xD;
      standard of care treatment versus percutaneous RVAD placement perioperatively to LVAD&#xD;
      implantation. The investigators hypothesize that the use of the RVAD will mitigate need for&#xD;
      inotropic support, reducing the vasoactive-inotrope score (VIS) by 50%, and will improve end&#xD;
      organ function in patients compared to standard of care.&#xD;
&#xD;
      Subjects who consent to the study will undergo peri-operative placement of an RVAD, which&#xD;
      will be left in up to 72 hours postoperatively. The type of RVAD (Impella RP or ProtekDuo)&#xD;
      inserted will be determined by patient needs and venous access and will be up to the&#xD;
      discretion of the treating physician. 25 subjects will be enrolled in the prospective&#xD;
      interventional cohort and compared to 25 subjects in the matched retrospective control&#xD;
      cohort.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prior studies have shown that left ventricular assist device (LVAD) implantation commonly&#xD;
      results in right ventricular failure (RVF). Right ventricular dysfunction and failure after&#xD;
      LVAD implantation is known to increase morbidity and mortality and contribute to longer&#xD;
      post-implant hospital length of stay. More severe right ventricular failure is highly&#xD;
      correlated with poor prognosis and death post-LVAD implantation. In current practice,&#xD;
      patients who receive LVADs require right heart support, provided in the form of inotropes.&#xD;
      Vasoactive inotrope score (VIS) is a measure that quantifies the amount of right heart&#xD;
      support required post-operatively, including dopamine, dobutamine, milrinone, epinephrine,&#xD;
      norepinephrine, and vasopressin. It has been used in other studies as a surrogate marker for&#xD;
      hemodynamic cardiovascular derangement.&#xD;
&#xD;
      In some cases, right ventricular failure post-LVAD also requires mechanical circulatory&#xD;
      support during the perioperative period. Since RVF is difficult to predict and can have&#xD;
      harmful effects such as increased ICU stay, adverse outcomes, and mortality, it could be&#xD;
      beneficial to preemptively treat patients through preoperative or intraoperative percutaneous&#xD;
      right ventricular assist device (RVAD) placement to prevent RVF. The purpose of this study is&#xD;
      to test the hypothesis that preemptive use of percutaneous RVADs will mitigate the need for&#xD;
      inotropic support in LVAD patients, reducing associated adverse outcomes.&#xD;
&#xD;
      This trial will include both a prospective interventional cohort and a retrospective control&#xD;
      cohort. The prospective interventional cohort will consist of patients undergoing LVAD&#xD;
      implantation at Massachusetts General Hospital. These patients will receive an RVAD (either&#xD;
      the ProtekDuo or Impella RP) prior to or during LVAD implantation. The historical control&#xD;
      cohort will consist of retrospective data collection on patients who have undergone LVAD&#xD;
      implantation in the past. This group will be matched with the enrolled prospective&#xD;
      interventional patients. The purpose of this study is to compare clinical outcomes of&#xD;
      standard of care treatment versus preemptive percutaneous RVAD placement surrounding LVAD&#xD;
      implantation. The investigators hypothesize that the use of the RVAD will mitigate need for&#xD;
      inotropic support, reducing the vasoactive-inotrope score (VIS) by 50%, and will improve end&#xD;
      organ function in patients compared to standard of care.&#xD;
&#xD;
      There are two types of percutaneous RVADs that will be used in the study: the Impella RP and&#xD;
      the ProtekDuo. These devices allow for early intervention in RVF without the need for&#xD;
      invasive surgical procedures requiring placement of durable RVADs via thoracotomy or&#xD;
      sternotomy. The Impella RP, manufactured by Abiomed, is a heart pump that delivers blood from&#xD;
      the inferior vena cava (IVC) to the pulmonary artery (PA). Its insertion is done&#xD;
      percutaneously via catheterization through the femoral vein. ProtekDuo, manufactured by&#xD;
      TandemLife, is another device placed percutaneously for right heart support via the right&#xD;
      internal jugular (RIJ) vein.&#xD;
&#xD;
      Subjects who consent to the study will undergo pre-operative or intra-operative placement of&#xD;
      an RVAD, which will be left in up to 72 hours postoperatively. The type of RVAD (Impella RP&#xD;
      or ProtekDuo) inserted will be determined by patient needs and venous access and will be up&#xD;
      to the discretion of the treating physician. 25 subjects will be enrolled in the prospective&#xD;
      interventional cohort and compared to 25 subjects in the matched retrospective control&#xD;
      cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Vasoactive Inotropic Score</measure>
    <time_frame>first 24 hours post-LVAD implantation</time_frame>
    <description>Retrospective review in a patient chart. Score calculated based on dosages of vasopressors and inotropes within first 24-hours post-LVAD implant. It is hypothesized that a higher score will correspond with worse outcomes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Vasoactive Inotropic Score</measure>
    <time_frame>up to date of hospital discharge (estimated average = 3 weeks)</time_frame>
    <description>Retrospective review in a patient chart. Calculated based on dosages of inotropes and vasopressors from time of LVAD implantation to hospital discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive Care Unit length of stay</measure>
    <time_frame>up to date of discharge from intensive care unit (estimated average = 1 week)</time_frame>
    <description>Retrospective review in a patient chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total post-operative length of stay after LVAD implantation</measure>
    <time_frame>up to date of hospital discharge (estimated average = 3 weeks)</time_frame>
    <description>Retrospective review in a patient chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival at discharge after LVAD placement</measure>
    <time_frame>up to date of hospital discharge (estimated average = 3 weeks)</time_frame>
    <description>Retrospective review in a patient chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival at 1 year after LVAD placement or heart transplant</measure>
    <time_frame>up to 1 year post-LVAD implantation</time_frame>
    <description>Retrospective review in a patient chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>End organ dysfunction</measure>
    <time_frame>up to 1 year post-LVAD implantation</time_frame>
    <description>end organ dysfunction including 1) Development of acute kidney injury (AKI) - defined as increase in serum creatinine (sCr) to 4mg/dl or greater, a 150 percent or greater increase in sCr over the baseline preoperative value, or a new requirement for renal replacement therapy; 2) Liver dysfunction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LVAD Device Speed</measure>
    <time_frame>measured up to 1 year post-LVAD implantation</time_frame>
    <description>Retrospective review in a patient chart</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>prospective interventional cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The prospective interventional cohort will consist of patients undergoing LVAD implantation at Massachusetts General Hospital. These patients will receive an RVAD (either the ProtekDuo or Impella RP) prior to or during LVAD implantation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>retrospective control cohort</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The historical control cohort will consist of retrospective data collection on patients who have undergone LVAD implantation in the past. This group will be age and sex matched with the enrolled prospective interventional patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Percutaneous RVAD</intervention_name>
    <description>ProtekDuo or Impella RP</description>
    <arm_group_label>prospective interventional cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 18-75&#xD;
&#xD;
          -  Accepted for LVAD implantation by MGH multidisciplinary team&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Disorders of the pulmonary artery wall that would preclude placement or correct&#xD;
             positioning of RVAD&#xD;
&#xD;
          -  Presence of mechanical valves&#xD;
&#xD;
          -  Mural thrombosis of the right atrium or vena cava&#xD;
&#xD;
          -  Anatomic conditions precluding insertion of the RVAD&#xD;
&#xD;
          -  Complicated venous access precluding or complicating device placement (i.e. femoral&#xD;
             and jugular thrombosis)&#xD;
&#xD;
          -  No evidence of right ventricular dysfunction by echocardiogram&#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>David D'Alessandro, MD</last_name>
    <phone>617-726-8841</phone>
    <email>DADALESSANDRO@MGH.HARVARD.EDU</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kamila Drezek</last_name>
    <phone>617-724-2610</phone>
    <email>kdrezek@mgh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>January 7, 2022</last_update_submitted>
  <last_update_submitted_qc>January 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>David A. D'Alessandro, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 5, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT04458103/Prot_002.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04458103
org study id: 2020P000422
nct id: NCT04458103
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
Prior studies have shown that left ventricular assist device (LVAD) implantation commonly
      results in right ventricular failure (RVF). Right ventricular dysfunction and failure after
      LVAD implantation is known to increase morbidity and mortality and contribute to longer
      post-implant hospital length of stay. Since RVF is difficult to predict and can have harmful
      effects such as increased ICU stay, adverse outcomes, and mortality, it could be beneficial
      to preemptively treat patients through preoperative or intraoperative percutaneous right
      ventricular assist device (RVAD) placement to prevent RVF.

      This trial will include both a prospective interventional cohort and a retrospective control
      cohort. The prospective interventional cohort will consist of patients undergoing LVAD
      implantation at Massachusetts General Hospital. These patients will preemptively receive an
      RVAD (either the ProtekDuo or Impella RP) surrounding LVAD implantation. The historical
      control cohort will consist of retrospective data collection on patients who have undergone
      LVAD implantation in the past. This group will be matched with the enrolled prospective
      interventional patients. The purpose of this study is to compare clinical outcomes of
      standard of care treatment versus percutaneous RVAD placement perioperatively to LVAD
      implantation. The investigators hypothesize that the use of the RVAD will mitigate need for
      inotropic support, reducing the vasoactive-inotrope score (VIS) by 50%, and will improve end
      organ function in patients compared to standard of care.

      Subjects who consent to the study will undergo peri-operative placement of an RVAD, which
      will be left in up to 72 hours postoperatively. The type of RVAD (Impella RP or ProtekDuo)
      inserted will be determined by patient needs and venous access and will be up to the
      discretion of the treating physician. 25 subjects will be enrolled in the prospective
      interventional cohort and compared to 25 subjects in the matched retrospective control
      cohort.
Prior studies have shown that left ventricular assist device (LVAD) implantation commonly
      results in right ventricular failure (RVF). Right ventricular dysfunction and failure after
      LVAD implantation is known to increase morbidity and mortality and contribute to longer
      post-implant hospital length of stay. More severe right ventricular failure is highly
      correlated with poor prognosis and death post-LVAD implantation. In current practice,
      patients who receive LVADs require right heart support, provided in the form of inotropes.
      Vasoactive inotrope score (VIS) is a measure that quantifies the amount of right heart
      support required post-operatively, including dopamine, dobutamine, milrinone, epinephrine,
      norepinephrine, and vasopressin. It has been used in other studies as a surrogate marker for
      hemodynamic cardiovascular derangement.

      In some cases, right ventricular failure post-LVAD also requires mechanical circulatory
      support during the perioperative period. Since RVF is difficult to predict and can have
      harmful effects such as increased ICU stay, adverse outcomes, and mortality, it could be
      beneficial to preemptively treat patients through preoperative or intraoperative percutaneous
      right ventricular assist device (RVAD) placement to prevent RVF. The purpose of this study is
      to test the hypothesis that preemptive use of percutaneous RVADs will mitigate the need for
      inotropic support in LVAD patients, reducing associated adverse outcomes.

      This trial will include both a prospective interventional cohort and a retrospective control
      cohort. The prospective interventional cohort will consist of patients undergoing LVAD
      implantation at Massachusetts General Hospital. These patients will receive an RVAD (either
      the ProtekDuo or Impella RP) prior to or during LVAD implantation. The historical control
      cohort will consist of retrospective data collection on patients who have undergone LVAD
      implantation in the past. This group will be matched with the enrolled prospective
      interventional patients. The purpose of this study is to compare clinical outcomes of
      standard of care treatment versus preemptive percutaneous RVAD placement surrounding LVAD
      implantation. The investigators hypothesize that the use of the RVAD will mitigate need for
      inotropic support, reducing the vasoactive-inotrope score (VIS) by 50%, and will improve end
      organ function in patients compared to standard of care.

      There are two types of percutaneous RVADs that will be used in the study: the Impella RP and
      the ProtekDuo. These devices allow for early intervention in RVF without the need for
      invasive surgical procedures requiring placement of durable RVADs via thoracotomy or
      sternotomy. The Impella RP, manufactured by Abiomed, is a heart pump that delivers blood from
      the inferior vena cava (IVC) to the pulmonary artery (PA). Its insertion is done
      percutaneously via catheterization through the femoral vein. ProtekDuo, manufactured by
      TandemLife, is another device placed percutaneously for right heart support via the right
      internal jugular (RIJ) vein.

      Subjects who consent to the study will undergo pre-operative or intra-operative placement of
      an RVAD, which will be left in up to 72 hours postoperatively. The type of RVAD (Impella RP
      or ProtekDuo) inserted will be determined by patient needs and venous access and will be up
      to the discretion of the treating physician. 25 subjects will be enrolled in the prospective
      interventional cohort and compared to 25 subjects in the matched retrospective control
      cohort.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Vasoactive Inotropic Score
time frame: first 24 hours post-LVAD implantation
description: Retrospective review in a patient chart. Score calculated based on dosages of vasopressors and inotropes within first 24-hours post-LVAD implant. It is hypothesized that a higher score will correspond with worse outcomes.
measure: Total Vasoactive Inotropic Score
time frame: up to date of hospital discharge (estimated average = 3 weeks)
description: Retrospective review in a patient chart. Calculated based on dosages of inotropes and vasopressors from time of LVAD implantation to hospital discharge.
measure: Intensive Care Unit length of stay
time frame: up to date of discharge from intensive care unit (estimated average = 1 week)
description: Retrospective review in a patient chart
measure: Total post-operative length of stay after LVAD implantation
time frame: up to date of hospital discharge (estimated average = 3 weeks)
description: Retrospective review in a patient chart
measure: Survival at discharge after LVAD placement
time frame: up to date of hospital discharge (estimated average = 3 weeks)
description: Retrospective review in a patient chart
measure: Survival at 1 year after LVAD placement or heart transplant
time frame: up to 1 year post-LVAD implantation
description: Retrospective review in a patient chart
measure: End organ dysfunction
time frame: up to 1 year post-LVAD implantation
description: end organ dysfunction including 1) Development of acute kidney injury (AKI) - defined as increase in serum creatinine (sCr) to 4mg/dl or greater, a 150 percent or greater increase in sCr over the baseline preoperative value, or a new requirement for renal replacement therapy; 2) Liver dysfunction
measure: LVAD Device Speed
time frame: measured up to 1 year post-LVAD implantation
description: Retrospective review in a patient chart
arm group label: prospective interventional cohort
arm group type: Experimental
description: The prospective interventional cohort will consist of patients undergoing LVAD implantation at Massachusetts General Hospital. These patients will receive an RVAD (either the ProtekDuo or Impella RP) prior to or during LVAD implantation.
arm group label: retrospective control cohort
arm group type: No Intervention
description: The historical control cohort will consist of retrospective data collection on patients who have undergone LVAD implantation in the past. This group will be age and sex matched with the enrolled prospective interventional patients.
intervention type: Device
intervention name: Percutaneous RVAD
description: ProtekDuo or Impella RP
arm group label: prospective interventional cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: David D'Alessandro, MD
phone: 617-726-8841
email: DADALESSANDRO@MGH.HARVARD.EDU
last name: Kamila Drezek
phone: 617-724-2610
email: kdrezek@mgh.harvard.edu
facility: 
status: Recruiting
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: David A. D'Alessandro, M.D.
investigator title: Principal Investigator
mesh term: Heart Failure
sharing ipd: No
provided document: 