<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/NCT02226679</url>
  </required_header>
  <id_info>
    <org_study_id>LSH-11-001</org_study_id>
    <nct_id>NCT02226679</nct_id>
  </id_info>
  <brief_title>An Open Label Rollover Trial for Patients Randomized to the Control Group of Study LSH-10-001</brief_title>
  <official_title>An Open Label Rollover Trial for Patients Randomized to the Control Group of Study LSH-10-001 (Rollover Study for AUGMENT-HF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LoneStar Heart, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LoneStar Heart, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this extension study is to evaluate the safety and potential beneficial&#xD;
      effects of the Algisyl-LVR™ device in patients with established heart failure secondary to a&#xD;
      dilated cardiomyopathy. The results of this study will provide confirmatory evidence of the&#xD;
      long-term safety and effectiveness of the Algisyl-LVR in patients with established heart&#xD;
      failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, open-label evaluation of the safety and effectiveness of Algisyl-LVR&#xD;
      in patients with dilated cardiomyopathy of either ischemic or non-ischemic origin. The&#xD;
      evaluation for the primary measure of efficacy (Peak VO2) at 6 months will be&#xD;
      investigator-blinded. The primary safety endpoint, while not blinded, is 30 day all-cause&#xD;
      mortality and an objective assessment. The remaining study endpoints will evaluate the&#xD;
      effects of the device through the evaluation of functional, structural, biochemical, and&#xD;
      electrocardiographic evaluations at 6 and 12 months. Evaluation of adverse events and these&#xD;
      assessments will also provide evidence of the safety profile of the device in patients with&#xD;
      dilated cardiomyopathy.&#xD;
&#xD;
      Pre-enrollment baseline patient evaluation will include clinical assessment, assessment of&#xD;
      New York Heart Association (NYHA) functional class, blood tests, transthoracic&#xD;
      echocardiography, MRI, electrocardiogram, cardiopulmonary exercise testing (CPX), submaximal&#xD;
      exercise testing, and quality of life assessments. Blinded central evaluation will be&#xD;
      performed for measures of cardiopulmonary exercise testing and cardiac imaging.&#xD;
&#xD;
      *Note: The local CPX and echocardiography measurements will be used to determine patient&#xD;
      eligibility with respect to the peak V02 values, ejection fraction and the left ventricular&#xD;
      end diastolic dimension indexed to body surface area (LVEDDi). The core lab values for these&#xD;
      same assessments will be used in all statistical analyses of the study.&#xD;
&#xD;
      Patient's eligible for this study completed at least 12 months of follow in the control group&#xD;
      of the lead-in study LSH-10-001 and provided a written informed consent to participate in&#xD;
      study LSH-001. A written informed consent to be enrolled in study LSH-11-001 is required for&#xD;
      all patients electing participation in this roll-over study. After written patient informed&#xD;
      consent has been obtained and verification of eligibility, patients who meet the inclusion&#xD;
      and exclusion criteria can be included in the study and will have the Algisyl-LVR™ device&#xD;
      (implants) administered during a surgical procedure. Patients will be considered part of this&#xD;
      study cohort as soon as they have been hospitalized to receive the Algisyl-LVR device. The&#xD;
      investigator will complete the &quot;Premature Withdrawal from Follow-up&quot; form in the patient's&#xD;
      eCRF for study LSH-10-001 and indicate &quot;Patient will receive the Algisyl-LVR device&quot; as the&#xD;
      reason for premature withdrawal from LSH-10-001. The acute response to device implant will be&#xD;
      monitored intraoperatively via continuous electrocardiographic cardiac monitoring, arterial&#xD;
      pressure lines, transesophageal echocardiography (TEE), and pulmonary artery catheter.&#xD;
      Patients receiving the investigational device are expected to remain hospitalized for 5 to 14&#xD;
      days.&#xD;
&#xD;
      Follow-up in this study is divided into two phases. During the first phase, referred to as&#xD;
      the &quot;efficacy phase&quot;, repeat testing of patient functional and cardiac structural parameters&#xD;
      will be conducted at follow-up visits scheduled at 3 months and 6 months, and every 6 months&#xD;
      thereafter. Follow-up testing will be supplemented by a 30 day (post implant) telephone&#xD;
      contact with all patients. The efficacy phase of the trial will end on a common closing date&#xD;
      after a minimum of 6 months of follow-up (i.e., after the last patient enrolled has been&#xD;
      completed the 6 month visit). At that point data analysis will be performed and an initial&#xD;
      study report will be generated. Following completion of the efficacy phase, long-term&#xD;
      monitoring will continue through each patient's 24-month visit. This second phase is referred&#xD;
      to as the &quot;extended follow-up phase&quot;. During this phase, data collection will be focused on&#xD;
      long-term safety and will be conducted at 6-month intervals.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2014</start_date>
  <completion_date type="Anticipated">April 2016</completion_date>
  <primary_completion_date type="Anticipated">April 2016</primary_completion_date>
  <phase>N/A</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>estimate the 30 day mortality associated with the implantation of the Algisyl-LVR device</measure>
    <time_frame>30 days</time_frame>
    <description>The primary safety objective is to estimate the 30 day mortality associated with the implantation of the Algisyl-LVR device</description>
  </primary_outcome>
  <other_outcome>
    <measure>Change in Peak VO2 from baseline to 6 months of follow-up</measure>
    <time_frame>6 months</time_frame>
    <description>Change in Peak VO2 from baseline to 6 months of follow-up</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cardiomyopathy</condition>
  <condition>Dilated Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>Algisyl-LVR device implantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Algisyl-LVR™ employed as a method of left ventricular augmentation and restoration in patients with dilated cardiomyopathy. Algisyl-LVR™ will be injected into the myocardium under direct visualization during the surgical procedure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Algisyl-LVR</intervention_name>
    <description>Algisyl-LVR™ device (implants) administered during a surgical procedure</description>
    <arm_group_label>Algisyl-LVR device implantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients who completed at least 12 months of follow in the control group of the&#xD;
             lead-in study LSH-10-001 are eligible to participate.&#xD;
&#xD;
             Patients must have completed all study related procedures for the 12 month, 18 month&#xD;
             or 24 month visit in Protocol LSH-10-001. Study procedures completed for the 12, 18 or&#xD;
             24 month visit in study LSH1-10-001 will be used as the baseline (screening) and&#xD;
             qualifying procedures for study LSH-11-001 if the procedure was performed within 60&#xD;
             days of the date of Algisyl-LVR implant (screening procedures outside this window must&#xD;
             be repeated).&#xD;
&#xD;
          2. The patients must be able and willing to give written informed consent&#xD;
&#xD;
          3. The patients will be adult (age ≥ 18 years and ≤ 79 years) males or females&#xD;
&#xD;
          4. The patients must be on stable, evidence-based therapy for heart failure&#xD;
&#xD;
             Evidence-based therapy for heart failure is defined as an ACE-inhibitor (ACE-I),&#xD;
             and/or angiotensin II receptor blockers (ARB) for patients at stable doses for 1 month&#xD;
             prior to enrollment, if tolerated, and a beta blocker (carvedilol, metoprolol&#xD;
             succinate, Nebivolol or bisoprolol) for 3 months prior to enrollment, if tolerated.&#xD;
             Recent up-titration of the beta blocker is acceptable if the patient has been stable&#xD;
             on this dose for 1 month prior to enrollment. Stable is defined as no more than a 100%&#xD;
             increase or a 50% decrease in dose. Contraindications or intolerance to therapies&#xD;
             should be documented. In those intolerant to both ACE-I and ARB, combination therapy&#xD;
             with hydralazine and oral nitrate should be considered. Therapeutic equivalence for&#xD;
             ACE-I substitutions is allowed within the enrollment stability timelines. Aldosterone&#xD;
             inhibitor therapy should be added when NYHA Class III or IV symptoms occur on standard&#xD;
             therapy. If aldosterone inhibitor therapy is to be administered in NYHA Class II&#xD;
             patients, it must be initiated and optimized prior to enrollment. Eplerenone requires&#xD;
             dosage stability for 1 month prior to enrollment. Diuretics should be used as&#xD;
             necessary to keep the patient euvolemic. All heart failure therapeutics and dosages&#xD;
             should be documented in the Case Report Forms.&#xD;
&#xD;
             * Note: CRT or CRT-D are acceptable co-therapy, if placed &gt; 3 months before implant of&#xD;
             Algisyl-LVR or the investigator does not anticipate within 6 months after enrollment&#xD;
&#xD;
          5. The patients will have a left ventricular ejection fraction equal to or less than 35%&#xD;
             via echocardiography, cardiac catheterization, radionuclide scan, or magnetic&#xD;
             resonance imaging (measured within the last 30 days)&#xD;
&#xD;
          6. The patients will have a left ventricular end diastolic dimension indexed to body&#xD;
             surface area (LVEDDi) of 30 to 40mm/m2 (LVEDD/BSA) (measured within the last 30 days).&#xD;
&#xD;
          7. Patients must have symptomatic heart failure with a Peak VO2 of 9.0 - 14.5 ml/min/kg&#xD;
             (performed using a bicycle ergometer). Patients must perform two CPX tests (within 60&#xD;
             days of the Algisyl-LVR procedure and performed at least 20 hours apart) that differ&#xD;
             by no more than 15% in the observed value for Peak VO2 and have a mean value of 9.0 -&#xD;
             14.5 ml/min/kg from these two tests.&#xD;
&#xD;
          8. Patient's surgical risk must be considered reasonable and the evaluation of surgical&#xD;
             risk should include review of coronary and left ventricular angiography.&#xD;
&#xD;
          9. If female, the patients must be (a) post-menopausal, (b) surgically sterile, or (c)&#xD;
             using adequate birth control and have a negative serum pregnancy test within 7 days&#xD;
             prior to administration of study device.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients for whom it is planned to receive CABG, MVR, heart transplantation or LVAD&#xD;
             within the next 6 months&#xD;
&#xD;
          2. Patients presenting with cardiogenic shock&#xD;
&#xD;
          3. Patients who have undergone a previous mid-sternotomy surgical procedure are excluded&#xD;
             unless the surgeon's assessment is that the left sided limited thoracotomy is feasible&#xD;
             and considered reasonable surgical risk&#xD;
&#xD;
          4. Patients presenting with a restrictive cardiomyopathy such as due to amyloidosis,&#xD;
             sarcoidosis, or hemochromatosis&#xD;
&#xD;
          5. Patient with a history of constrictive pericarditis&#xD;
&#xD;
          6. Patients with a Q wave myocardial infarction (MI) within the last 30 days&#xD;
&#xD;
          7. Patients with a recent history of stroke (within 60 days prior to the surgical&#xD;
             procedure)&#xD;
&#xD;
          8. A left ventricular (LV) wall thickness of the LV free-wall, at the mid-ventricular&#xD;
             level, of less than 8 mm (screening echocardiography must confirm a minimum wall&#xD;
             thickness of 8 mm)&#xD;
&#xD;
          9. Patients with a serum creatinine &gt; 2.5 mg/dL&#xD;
&#xD;
         10. Clinically significant liver enzyme abnormalities, i.e., AST(SGOT) and ALT (SGPT) more&#xD;
             than 2.5 times the upper limit of normal&#xD;
&#xD;
         11. History of severe COPD (i.e., FEV 1&lt; 1 liter or FEV1 &lt; 50% predicted)&#xD;
&#xD;
         12. The patients will not be receiving concurrently an investigational Product in another&#xD;
             clinical trial or have received an investigational Product in another clinical trial&#xD;
             in the 30 days prior to enrollment&#xD;
&#xD;
         13. A life expectancy of less than 1 year or any other condition that, in the opinion of&#xD;
             the clinical investigator, might compromise any aspect of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ionel Droc, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emergency Clinic Center for The Army For the Cardiovascular Diseases</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>A.O. Istituti Ospitalieri di Cremona&quot;.</name>
      <address>
        <city>Cremona</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency Clinic Center of The Army for The Cardiovascular Diseases</name>
      <address>
        <city>Bucharest</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Romania</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>August 25, 2014</last_update_submitted>
  <last_update_submitted_qc>August 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>crossover</keyword>
  <keyword>rollover study</keyword>
  <keyword>open label</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Dilated</mesh_term>
  </condition_browse>
  <!-- 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/NCT02226679
org study id: LSH-11-001
nct id: NCT02226679
lead sponsor: 
has dmc: Yes
The objective of this extension study is to evaluate the safety and potential beneficial
      effects of the Algisyl-LVR™ device in patients with established heart failure secondary to a
      dilated cardiomyopathy. The results of this study will provide confirmatory evidence of the
      long-term safety and effectiveness of the Algisyl-LVR in patients with established heart
      failure.
This is a prospective, open-label evaluation of the safety and effectiveness of Algisyl-LVR
      in patients with dilated cardiomyopathy of either ischemic or non-ischemic origin. The
      evaluation for the primary measure of efficacy (Peak VO2) at 6 months will be
      investigator-blinded. The primary safety endpoint, while not blinded, is 30 day all-cause
      mortality and an objective assessment. The remaining study endpoints will evaluate the
      effects of the device through the evaluation of functional, structural, biochemical, and
      electrocardiographic evaluations at 6 and 12 months. Evaluation of adverse events and these
      assessments will also provide evidence of the safety profile of the device in patients with
      dilated cardiomyopathy.

      Pre-enrollment baseline patient evaluation will include clinical assessment, assessment of
      New York Heart Association (NYHA) functional class, blood tests, transthoracic
      echocardiography, MRI, electrocardiogram, cardiopulmonary exercise testing (CPX), submaximal
      exercise testing, and quality of life assessments. Blinded central evaluation will be
      performed for measures of cardiopulmonary exercise testing and cardiac imaging.

      *Note: The local CPX and echocardiography measurements will be used to determine patient
      eligibility with respect to the peak V02 values, ejection fraction and the left ventricular
      end diastolic dimension indexed to body surface area (LVEDDi). The core lab values for these
      same assessments will be used in all statistical analyses of the study.

      Patient's eligible for this study completed at least 12 months of follow in the control group
      of the lead-in study LSH-10-001 and provided a written informed consent to participate in
      study LSH-001. A written informed consent to be enrolled in study LSH-11-001 is required for
      all patients electing participation in this roll-over study. After written patient informed
      consent has been obtained and verification of eligibility, patients who meet the inclusion
      and exclusion criteria can be included in the study and will have the Algisyl-LVR™ device
      (implants) administered during a surgical procedure. Patients will be considered part of this
      study cohort as soon as they have been hospitalized to receive the Algisyl-LVR device. The
      investigator will complete the "Premature Withdrawal from Follow-up" form in the patient's
      eCRF for study LSH-10-001 and indicate "Patient will receive the Algisyl-LVR device" as the
      reason for premature withdrawal from LSH-10-001. The acute response to device implant will be
      monitored intraoperatively via continuous electrocardiographic cardiac monitoring, arterial
      pressure lines, transesophageal echocardiography (TEE), and pulmonary artery catheter.
      Patients receiving the investigational device are expected to remain hospitalized for 5 to 14
      days.

      Follow-up in this study is divided into two phases. During the first phase, referred to as
      the "efficacy phase", repeat testing of patient functional and cardiac structural parameters
      will be conducted at follow-up visits scheduled at 3 months and 6 months, and every 6 months
      thereafter. Follow-up testing will be supplemented by a 30 day (post implant) telephone
      contact with all patients. The efficacy phase of the trial will end on a common closing date
      after a minimum of 6 months of follow-up (i.e., after the last patient enrolled has been
      completed the 6 month visit). At that point data analysis will be performed and an initial
      study report will be generated. Following completion of the efficacy phase, long-term
      monitoring will continue through each patient's 24-month visit. This second phase is referred
      to as the "extended follow-up phase". During this phase, data collection will be focused on
      long-term safety and will be conducted at 6-month intervals.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: estimate the 30 day mortality associated with the implantation of the Algisyl-LVR device
time frame: 30 days
description: The primary safety objective is to estimate the 30 day mortality associated with the implantation of the Algisyl-LVR device
measure: Change in Peak VO2 from baseline to 6 months of follow-up
time frame: 6 months
description: Change in Peak VO2 from baseline to 6 months of follow-up
arm group label: Algisyl-LVR device implantation
arm group type: Experimental
description: Algisyl-LVR™ employed as a method of left ventricular augmentation and restoration in patients with dilated cardiomyopathy. Algisyl-LVR™ will be injected into the myocardium under direct visualization during the surgical procedure.
intervention type: Device
intervention name: Algisyl-LVR
description: Algisyl-LVR™ device (implants) administered during a surgical procedure
arm group label: Algisyl-LVR device implantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Ionel Droc, MD
role: Principal Investigator
affiliation: Emergency Clinic Center for The Army For the Cardiovascular Diseases
facility: 
facility: 
country: Italy
country: Romania
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Dilated