<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/NCT01707225</url>
  </required_header>
  <id_info>
    <org_study_id>HM14516</org_study_id>
    <nct_id>NCT01707225</nct_id>
  </id_info>
  <brief_title>Safety Study of Octreotide Injection to Prevent GI Bleeding in Patients With Left Ventricular Assist Device (LVAD)</brief_title>
  <official_title>Safety and Efficacy of Octreotide LAR Depot in Left Ventricular Assist Device (LVAD) Associate Gastrointestinal (GI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Thoratec Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that octreotide LAR (Long Acting Release) safely decreases GI&#xD;
      bleeding in patients with a left ventricular assist device (LVAD). Patients undergoing&#xD;
      implantation of non-pulsatile, continuous-flow LVAD have a higher incidence of&#xD;
      gastrointestinal bleeding. This is a significantly associated morbidity and can threaten a&#xD;
      patient's life as well as their ability to undergo eventual heart transplantation secondary&#xD;
      to both general health/strength and the potential development of antibodies to blood products&#xD;
      that would make future transfusions and transplantations more difficult.&#xD;
&#xD;
      If this research finds that use of octreotide LAR can decrease the incidence of&#xD;
      gastrointestinal bleeding in this patient population, it will revolutionize the manner in&#xD;
      which these patients are managed. The finding of reduced GI bleeding would allow the patient&#xD;
      to have less exposure to blood products, reduce hospitalizations, and ensure that subsequent&#xD;
      transplant planning not be delayed. This would not only be of great benefit to the patient,&#xD;
      but would significantly decrease health-care costs through preventive measures.&#xD;
&#xD;
      The goal of this project is to study whether the regular administration of monthly octreotide&#xD;
      LAR is safe and if it will decrease the incidence of gastrointestinal bleeding in patients&#xD;
      undergoing implantation of non-pulsatile, continuous flow left ventricular assist devices&#xD;
      (LVAD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary specific aim is to determine the safety of octreotide LAR in patients with a&#xD;
      LVAD.&#xD;
&#xD;
      Patient experience of the following will be assessed throughout the study (list obtained from&#xD;
      up-to-date.com)&#xD;
&#xD;
      Cardiovascular:&#xD;
&#xD;
      Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)&#xD;
&#xD;
      Central nervous system:&#xD;
&#xD;
      Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness&#xD;
      (5% to 20%) Pain (4% to 15%)&#xD;
&#xD;
      Dermatologic:&#xD;
&#xD;
      Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)&#xD;
&#xD;
      Endocrine &amp; metabolic:&#xD;
&#xD;
      Hyperglycemia (2% to 27%)&#xD;
&#xD;
      Gastrointestinal:&#xD;
&#xD;
      Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%)&#xD;
      flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9%&#xD;
      to 21%) vomiting (4% to 21%)&#xD;
&#xD;
      Hematologic Anemia (5-15%)&#xD;
&#xD;
      Local:&#xD;
&#xD;
      Injection site pain (2% to 50%; dose and formulation related)&#xD;
&#xD;
      Neuromuscular &amp; skeletal:&#xD;
&#xD;
      Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)&#xD;
&#xD;
      Renal Kidney Stones (5-15%)&#xD;
&#xD;
      Respiratory:&#xD;
&#xD;
      Upper respiratory infection (10% to 23%)&#xD;
&#xD;
      Miscellaneous:&#xD;
&#xD;
      flu symptoms (1% to 20%)&#xD;
&#xD;
      Our key secondary outcomes will focus on study drug efficacy. Patient experience of the&#xD;
      following will be assessed:&#xD;
&#xD;
      Need for Blood Transfusion Hospital Admission for GI Bleed&#xD;
&#xD;
      Heart disease is a leading cause of death and disability, according to the American Heart&#xD;
      Association. Current therapies include lifestyle modification, medical management and&#xD;
      revascularization via Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass&#xD;
      Surgery (CABG). However, a large portion of patients develop cardiomyopathy which is&#xD;
      refractory to the above interventions. They are treated with chronic inotropes,&#xD;
      resynchronization and other forms of medical management.&#xD;
&#xD;
      Many of these patients eventually worsen and need consideration for cardiac transplantation.&#xD;
      The Thoratec Heartmate II, which is the primary left ventricular assist device (LVAD)&#xD;
      implanted at our institution, has been used as a bridge-to-transplantation. More recently it&#xD;
      has been approved as destination therapy for patients who are not candidates for&#xD;
      transplantation. Over 6000 of these devices have been implanted worldwide since their&#xD;
      introduction. We have implanted over 70 here at the VCU Health System and the McGuire VA&#xD;
      Medical Center.&#xD;
&#xD;
      The early LVAD devices provided physiologic pulsatility, but were large in size and required&#xD;
      large catheters for external venting. The newer continuous flow LVAD devices, such as the&#xD;
      Heartmate II, offer the benefit of being smaller and easier to implant as well as improving&#xD;
      mobility and thus quality of life. However, this benefit comes with a complication of an&#xD;
      increased incidence of GI bleeding, thought to be related to the loss of pulsatility and the&#xD;
      nature of these smaller devices.&#xD;
&#xD;
      Approximately 10-30% of patients experience at least one episode GI bleeding which is likely&#xD;
      multifactorial. It has already been demonstrated that an acquired von Willebrand Syndrome&#xD;
      (vWS) develops due to destruction of multimeric vWF. Additionally, it has been shown that&#xD;
      these patients have a higher than normal percentage of gastrointestinal angiodysplasia.&#xD;
      Whether these are preexisting or develop as a result of de novo angiogenesis from the gut&#xD;
      mucosa is unknown. It is thought that the loss of pulsatility and potential hypoxia result in&#xD;
      secretion of angiogenic mediators and contribute to the development of angiodysplasia.&#xD;
&#xD;
      Current treatment for LVAD associated GI bleeding is aimed at identifying the location of&#xD;
      bleeding and treatment with blood product transfusion, cryoprecipitate for vWS, Desmopressin&#xD;
      for platelet dysfunction, and interventions through Interventional Radiology (IR) and&#xD;
      surgery. In addition to the obvious costs and increase in morbidity and mortality associated&#xD;
      with the above therapies, patients who receive multiple transfusions develop antibodies and&#xD;
      thus become more difficult to transplant. Thus a vicious cycle develops.&#xD;
&#xD;
      We need to strive for a proactive stance in these patients and attack the problem at the&#xD;
      source. There is a considerable amount of experience using octreotide in idiopathic chronic&#xD;
      GI bleeding. This is likely due to its ability to decrease splanchnic blood flow and its&#xD;
      potential ability to inhibit angiogenesis. Octreotide has been thoroughly studied and has a&#xD;
      known safety profile. Off label use of octreotide LAR for the purpose of attenuating LVAD&#xD;
      associated GI bleeding is currently practiced by some physicians at VCU with no adverse side&#xD;
      effects encountered. It is time to formally study the safety and efficacy of octreotide LAR&#xD;
      for this purpose. We propose an open-label safety study for 10 subjects to be followed for a&#xD;
      total of 24 weeks. Should the safety study be favorably completed, a multi-center trial with&#xD;
      randomization to octreotide LAR or placebo with endpoints of GI bleeding and transfusion will&#xD;
      be pursued.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Side-Effects</measure>
    <time_frame>24 weeks</time_frame>
    <description>Cardiovascular:&#xD;
Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)&#xD;
Central nervous system:&#xD;
Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness (5% to 20%) Pain (4% to 15%)&#xD;
Dermatologic:&#xD;
Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)&#xD;
Endocrine &amp; metabolic:&#xD;
Hyperglycemia (2% to 27%)&#xD;
Gastrointestinal:&#xD;
Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%) flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9% to 21%) vomiting (4% to 21%)&#xD;
Hematologic Anemia (5-15%)&#xD;
Local:&#xD;
Injection site pain (2% to 50%; dose and formulation related)&#xD;
Neuromuscular &amp; skeletal:&#xD;
Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)&#xD;
Renal Kidney Stones (5-15%)&#xD;
Respiratory:&#xD;
Upper respiratory infection (10% to 23%)&#xD;
Miscellaneous:&#xD;
flu symptoms (1% to 20%)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Need for Blood Transfusion and Hospital Admission for GI Bleed</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Gastrointestinal Bleeding</condition>
  <arm_group>
    <arm_group_label>Octreotide LAR Depot</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once enrolled in the study subjects will receive a monthly intra-muscular injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Octreotide LAR Depot</intervention_name>
    <description>The subject will be seen in clinic every 4 weeks (+/- 4 days) through week 24. During weeks 25-36 the subject will receive a telephone call every 4 weeks +/- 4 days, from the research nurse to assess for changes occurring after the study drug was stopped. Subjects will receive a physical exam and interview at each visit to assess for any sign of GI bleeding at home as per standard protocol for HeartMate II patients and for potential drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
    <arm_group_label>Octreotide LAR Depot</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  LVAD insertion as bridge to transplant or destination&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Poorly controlled diabetes, A1C greater than 8%&#xD;
&#xD;
          -  Poorly controlled hypothyroidism, TSH &gt; upper limit of normal (5.5)&#xD;
&#xD;
          -  End Stage Renal Disease (ESRD) requiring dialysis&#xD;
&#xD;
          -  Cirrhosis&#xD;
&#xD;
          -  Anemia (Hgb &lt; 8)&#xD;
&#xD;
          -  Acromegaly&#xD;
&#xD;
          -  Hx of chronic diarrhea - as determined by history of loose stool lasting longer than&#xD;
             2-4 weeks&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
&#xD;
          -  Incarceration or otherwise a ward of the state&#xD;
&#xD;
          -  Non-English speaking&#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>Rajiv Malhotra, DO MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>VCU</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University Health System</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <results_first_submitted>December 7, 2015</results_first_submitted>
  <results_first_submitted_qc>December 7, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 12, 2016</results_first_posted>
  <last_update_submitted>December 7, 2016</last_update_submitted>
  <last_update_submitted_qc>December 7, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GI Bleeding</keyword>
  <keyword>Gastrointestinal bleeding</keyword>
  <keyword>LVAD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Octreotide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Octreotide LAR Depot</title>
          <description>Once enrolled in the study subjects will receive a monthly IM injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.&#xD;
Octreotide LAR Depot: subject seen in clinic every 4 weeks (+/- 4 days) through week 24. Weeks 25-36 subject will receive a call every 4 weeks +/- 4 days, to assess for changes after the study drug was stopped. Subjects will receive a exam and interview at each visit to assess for GI bleeding at home and for drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Octreotide LAR Depot</title>
          <description>Once enrolled in the study subjects will receive a monthly IM injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.&#xD;
Octreotide LAR Depot: subject seen in clinic every 4 weeks (+/- 4 days) through week 24. Weeks 25-36 subject will receive a call every 4 weeks +/- 4 days, to assess for changes after the study drug was stopped. Subjects will receive a exam and interview at each visit to assess for GI bleeding at home and for drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Side-Effects</title>
        <description>Cardiovascular:&#xD;
Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)&#xD;
Central nervous system:&#xD;
Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness (5% to 20%) Pain (4% to 15%)&#xD;
Dermatologic:&#xD;
Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)&#xD;
Endocrine &amp; metabolic:&#xD;
Hyperglycemia (2% to 27%)&#xD;
Gastrointestinal:&#xD;
Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%) flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9% to 21%) vomiting (4% to 21%)&#xD;
Hematologic Anemia (5-15%)&#xD;
Local:&#xD;
Injection site pain (2% to 50%; dose and formulation related)&#xD;
Neuromuscular &amp; skeletal:&#xD;
Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)&#xD;
Renal Kidney Stones (5-15%)&#xD;
Respiratory:&#xD;
Upper respiratory infection (10% to 23%)&#xD;
Miscellaneous:&#xD;
flu symptoms (1% to 20%)</description>
        <time_frame>24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Octreotide LAR Depot</title>
            <description>Once enrolled in the study subjects will receive a monthly IM injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.&#xD;
Octreotide LAR Depot: subject seen in clinic every 4 weeks (+/- 4 days) through week 24. Weeks 25-36 subject will receive a call every 4 weeks +/- 4 days, to assess for changes after the study drug was stopped. Subjects will receive a exam and interview at each visit to assess for GI bleeding at home and for drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Side-Effects</title>
          <description>Cardiovascular:&#xD;
Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)&#xD;
Central nervous system:&#xD;
Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness (5% to 20%) Pain (4% to 15%)&#xD;
Dermatologic:&#xD;
Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)&#xD;
Endocrine &amp; metabolic:&#xD;
Hyperglycemia (2% to 27%)&#xD;
Gastrointestinal:&#xD;
Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%) flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9% to 21%) vomiting (4% to 21%)&#xD;
Hematologic Anemia (5-15%)&#xD;
Local:&#xD;
Injection site pain (2% to 50%; dose and formulation related)&#xD;
Neuromuscular &amp; skeletal:&#xD;
Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)&#xD;
Renal Kidney Stones (5-15%)&#xD;
Respiratory:&#xD;
Upper respiratory infection (10% to 23%)&#xD;
Miscellaneous:&#xD;
flu symptoms (1% to 20%)</description>
          <units>participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="0" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Need for Blood Transfusion and Hospital Admission for GI Bleed</title>
        <time_frame>24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Octreotide LAR Depot</title>
            <description>Once enrolled in the study subjects will receive a monthly IM injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.&#xD;
Octreotide LAR Depot: subject seen in clinic every 4 weeks (+/- 4 days) through week 24. Weeks 25-36 subject will receive a call every 4 weeks +/- 4 days, to assess for changes after the study drug was stopped. Subjects will receive a exam and interview at each visit to assess for GI bleeding at home and for drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Need for Blood Transfusion and Hospital Admission for GI Bleed</title>
          <units>participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="0" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Octreotide LAR Depot</title>
          <description>Once enrolled in the study subjects will receive a monthly IM injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.&#xD;
Octreotide LAR Depot: subject seen in clinic every 4 weeks (+/- 4 days) through week 24. Weeks 25-36 subject will receive a call every 4 weeks +/- 4 days, to assess for changes after the study drug was stopped. Subjects will receive a exam and interview at each visit to assess for GI bleeding at home and for drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Rajiv Malhotra, DO</name_or_title>
      <organization>Virginia Commonwealth University</organization>
      <phone>804-828-9071</phone>
      <email>rajiv.malhotra@vcuhealth.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01707225
org study id: HM14516
nct id: NCT01707225
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The investigators hypothesize that octreotide LAR (Long Acting Release) safely decreases GI
      bleeding in patients with a left ventricular assist device (LVAD). Patients undergoing
      implantation of non-pulsatile, continuous-flow LVAD have a higher incidence of
      gastrointestinal bleeding. This is a significantly associated morbidity and can threaten a
      patient's life as well as their ability to undergo eventual heart transplantation secondary
      to both general health/strength and the potential development of antibodies to blood products
      that would make future transfusions and transplantations more difficult.

      If this research finds that use of octreotide LAR can decrease the incidence of
      gastrointestinal bleeding in this patient population, it will revolutionize the manner in
      which these patients are managed. The finding of reduced GI bleeding would allow the patient
      to have less exposure to blood products, reduce hospitalizations, and ensure that subsequent
      transplant planning not be delayed. This would not only be of great benefit to the patient,
      but would significantly decrease health-care costs through preventive measures.

      The goal of this project is to study whether the regular administration of monthly octreotide
      LAR is safe and if it will decrease the incidence of gastrointestinal bleeding in patients
      undergoing implantation of non-pulsatile, continuous flow left ventricular assist devices
      (LVAD).
The primary specific aim is to determine the safety of octreotide LAR in patients with a
      LVAD.

      Patient experience of the following will be assessed throughout the study (list obtained from
      up-to-date.com)

      Cardiovascular:

      Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)

      Central nervous system:

      Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness
      (5% to 20%) Pain (4% to 15%)

      Dermatologic:

      Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)

      Endocrine & metabolic:

      Hyperglycemia (2% to 27%)

      Gastrointestinal:

      Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%)
      flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9%
      to 21%) vomiting (4% to 21%)

      Hematologic Anemia (5-15%)

      Local:

      Injection site pain (2% to 50%; dose and formulation related)

      Neuromuscular & skeletal:

      Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)

      Renal Kidney Stones (5-15%)

      Respiratory:

      Upper respiratory infection (10% to 23%)

      Miscellaneous:

      flu symptoms (1% to 20%)

      Our key secondary outcomes will focus on study drug efficacy. Patient experience of the
      following will be assessed:

      Need for Blood Transfusion Hospital Admission for GI Bleed

      Heart disease is a leading cause of death and disability, according to the American Heart
      Association. Current therapies include lifestyle modification, medical management and
      revascularization via Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass
      Surgery (CABG). However, a large portion of patients develop cardiomyopathy which is
      refractory to the above interventions. They are treated with chronic inotropes,
      resynchronization and other forms of medical management.

      Many of these patients eventually worsen and need consideration for cardiac transplantation.
      The Thoratec Heartmate II, which is the primary left ventricular assist device (LVAD)
      implanted at our institution, has been used as a bridge-to-transplantation. More recently it
      has been approved as destination therapy for patients who are not candidates for
      transplantation. Over 6000 of these devices have been implanted worldwide since their
      introduction. We have implanted over 70 here at the VCU Health System and the McGuire VA
      Medical Center.

      The early LVAD devices provided physiologic pulsatility, but were large in size and required
      large catheters for external venting. The newer continuous flow LVAD devices, such as the
      Heartmate II, offer the benefit of being smaller and easier to implant as well as improving
      mobility and thus quality of life. However, this benefit comes with a complication of an
      increased incidence of GI bleeding, thought to be related to the loss of pulsatility and the
      nature of these smaller devices.

      Approximately 10-30% of patients experience at least one episode GI bleeding which is likely
      multifactorial. It has already been demonstrated that an acquired von Willebrand Syndrome
      (vWS) develops due to destruction of multimeric vWF. Additionally, it has been shown that
      these patients have a higher than normal percentage of gastrointestinal angiodysplasia.
      Whether these are preexisting or develop as a result of de novo angiogenesis from the gut
      mucosa is unknown. It is thought that the loss of pulsatility and potential hypoxia result in
      secretion of angiogenic mediators and contribute to the development of angiodysplasia.

      Current treatment for LVAD associated GI bleeding is aimed at identifying the location of
      bleeding and treatment with blood product transfusion, cryoprecipitate for vWS, Desmopressin
      for platelet dysfunction, and interventions through Interventional Radiology (IR) and
      surgery. In addition to the obvious costs and increase in morbidity and mortality associated
      with the above therapies, patients who receive multiple transfusions develop antibodies and
      thus become more difficult to transplant. Thus a vicious cycle develops.

      We need to strive for a proactive stance in these patients and attack the problem at the
      source. There is a considerable amount of experience using octreotide in idiopathic chronic
      GI bleeding. This is likely due to its ability to decrease splanchnic blood flow and its
      potential ability to inhibit angiogenesis. Octreotide has been thoroughly studied and has a
      known safety profile. Off label use of octreotide LAR for the purpose of attenuating LVAD
      associated GI bleeding is currently practiced by some physicians at VCU with no adverse side
      effects encountered. It is time to formally study the safety and efficacy of octreotide LAR
      for this purpose. We propose an open-label safety study for 10 subjects to be followed for a
      total of 24 weeks. Should the safety study be favorably completed, a multi-center trial with
      randomization to octreotide LAR or placebo with endpoints of GI bleeding and transfusion will
      be pursued.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Side-Effects
time frame: 24 weeks
description: Cardiovascular:
Sinus bradycardia (19% to 25%) Hypertension (≤13%) conduction abnormalities (9% to 10%)
Central nervous system:
Fatigue (1% to 32%) headache (6% to 30%) malaise (16% to 20%) fever (16% to 20%) dizziness (5% to 20%) Pain (4% to 15%)
Dermatologic:
Pruritus (≤18%) Rash (15%; depot formulation) alopecia (≤13%)
Endocrine & metabolic:
Hyperglycemia (2% to 27%)
Gastrointestinal:
Abdominal pain (5% to 61%) loose stools (5% to 61%) nausea (5% to 61%) diarrhea (34% to 58%) flatulence (≤38%) cholelithiasis (13% to 38%; length of therapy dependent) constipation (9% to 21%) vomiting (4% to 21%)
Hematologic Anemia (5-15%)
Local:
Injection site pain (2% to 50%; dose and formulation related)
Neuromuscular & skeletal:
Back pain (1% to 27%) arthropathy (8% to 19%) myalgia (≤18%)
Renal Kidney Stones (5-15%)
Respiratory:
Upper respiratory infection (10% to 23%)
Miscellaneous:
flu symptoms (1% to 20%)
measure: Need for Blood Transfusion and Hospital Admission for GI Bleed
time frame: 24 weeks
arm group label: Octreotide LAR Depot
arm group type: Experimental
description: Once enrolled in the study subjects will receive a monthly intra-muscular injection of 20mg of octreotide LAR at each study visit for 24 weeks and will be followed for a total of 36 weeks.
intervention type: Drug
intervention name: Octreotide LAR Depot
description: The subject will be seen in clinic every 4 weeks (+/- 4 days) through week 24. During weeks 25-36 the subject will receive a telephone call every 4 weeks +/- 4 days, from the research nurse to assess for changes occurring after the study drug was stopped. Subjects will receive a physical exam and interview at each visit to assess for any sign of GI bleeding at home as per standard protocol for HeartMate II patients and for potential drug related side effects. Labs collected for research will include monthly basic metabolic panel (BMP), complete blood count (CBC), fructosamine and quarterly HGbA1C , VEGF, vWF, vWF activity assay, thyroid stimulating hormone (TSH), platelet function test and fibrinogen. Subjects will receive their monthly injection while in clinic for their every 4 weeks appointment. The subjects will be followed and data will be collected for 36 weeks, or for as long as they are enrolled in the study.
arm group label: Octreotide LAR Depot
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rajiv Malhotra, DO MS
role: Principal Investigator
affiliation: VCU
facility: 
country: United States
responsible party type: Sponsor
mesh term: Gastrointestinal Hemorrhage
mesh term: Hemorrhage
mesh term: Octreotide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 