<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/NCT02967991</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0281</org_study_id>
    <nct_id>NCT02967991</nct_id>
  </id_info>
  <brief_title>19 Versus 22-Gauge Needle for EUS-LB</brief_title>
  <acronym>EUSLB1922</acronym>
  <official_title>19 Versus 22-Gauge Fine Needle Biopsy (FNB) Needles for Endoscopic Ultrasound Guided Liver Biopsy (EUS-LB): A Prospective Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Geisinger Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Geisinger Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic liver disorders (CLD) are a major cause of morbidity and mortality for individuals in&#xD;
      the US. Though serologic analysis will often lead to a conclusive diagnosis, liver biopsy&#xD;
      remains an important method for helping to determine the etiology and stage of LD.&#xD;
      Percutaneous liver biopsy (PLB), transjugular liver biopsy (TLB) and surgical liver biopsy&#xD;
      (SLB) are alternative methods for obtaining hepatic tissue. In recent years endoscopic&#xD;
      ultrasound guided-liver biopsy (EUS-LB) has come to the forefront as a safe and effective&#xD;
      method for obtaining tissue in CLD. There are several studies of the safety of EUS-LB as well&#xD;
      as the adequacy of specimens obtained in this fashion. Most studies involve a 19-gauge&#xD;
      needle, therefore in this study the investigators hope to compare the tissue yields of a&#xD;
      22-gauge fine needle biopsy (FNB) needle, in comparison to conventional 19-gauge. The&#xD;
      investigators predict that 19 and 22 gauge FNB needle will demonstrate similar diagnostic&#xD;
      accuracy, with less visible blood artifact. Similarly the investigators predict the safety to&#xD;
      be equal.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      3 BACKGROUND AND SIGNIFICANCE Chronic liver disease has a number of causes, and leads to&#xD;
      significant mortality and morbidity in the United States. It has been estimated that roughly&#xD;
      36,000 individuals die annually from the burden of chronic liver disease, thus early&#xD;
      diagnosis and intervention are paramount to preventing such complications. Though serologic&#xD;
      markers and non-invasive diagnostic imaging modalities are used as a method for determining&#xD;
      the underlying disease process, these methods lack the specificity of determining etiology of&#xD;
      a patient's chronic liver disease. Therefore, liver biopsy remains the &quot;gold standard&quot; for&#xD;
      obtaining valuable diagnostic and prognostic information.&#xD;
&#xD;
      At present there exist several methods for liver tissue acquisition. The most widely accepted&#xD;
      method remains percutaneous route (PLB), which utilizes percussion or imaging to localization&#xD;
      the biopsy site. The issue with this approach is its potential complication of&#xD;
      post-procedural pain in up to 84%, bleeding in 1/2500-10,000 procedures, with under 1/10,000&#xD;
      of these cases being fatal. Another means for obtaining tissue samples is the transjugular&#xD;
      route (TLB), which also allows for portal pressure measurement, and is usually reserved for&#xD;
      patients with coagulopathy.&#xD;
&#xD;
      More recently, endoscopic ultrasound guided liver biopsy (EUS-LB) has been developed as a&#xD;
      newer LB technique. The feasibility of EUS-LB for liver lesions has been validated yielding&#xD;
      excellent diagnostic results in several studies. This technique has also been evaluated for&#xD;
      hepatic parenchymal disease with up to 90% diagnostic yield. Subsequently, EUS-LB using a&#xD;
      19-gauge needle was compared to percutaneous/transjugular routes showing at least&#xD;
      comparative, and in some instances improved sample acquisition, versus other methods.&#xD;
      Different 19-gauge needles have been utilized in this setting yielding variable diagnostic&#xD;
      specimens. However, there has yet to be comparison of 19 versus a 22-gauge core biopsy needle&#xD;
      for EUS-LB. The safety profile with the 19g needle is remarkably good; it seems logical that&#xD;
      a smaller needle would be at least as good, if not better.&#xD;
&#xD;
      Primary End Points&#xD;
&#xD;
        1. Proportion of cases for which a histologic diagnosis could be made based upon the amount&#xD;
           of tissue obtained with the needle (using total portal structures &gt; 5 or length of the&#xD;
           longest piece (LLP) &gt; 15 mm).&#xD;
&#xD;
        2. Number of portal tracts (PT) in the specimen&#xD;
&#xD;
        3. Aggregate specimen length (ASL), length of the longest piece (LLP), and degree of&#xD;
           fragmentation Secondary End Points&#xD;
&#xD;
      1. Presence of a visible core specimen 2. Presence of visible clots in specimen 3. Adverse&#xD;
      events (AE) and serious adverse events (SAE) 4 HYPOTHESIS AND SPECIFIC aims&#xD;
&#xD;
      4.1 Hypothesis The investigators predict that the 19-gauge needle and 22-gauge core needle&#xD;
      will have similar ability to obtain adequate EUS-LB specimens 4.2 Specific Aim 1 To determine&#xD;
      the adequacy of EUS-LB using a 22-gauge core needle as compared with 19-gauge needle 4.3&#xD;
      Specific Aim 2 To determine if the 22-gauge core needle will demonstrate less blood artifact&#xD;
      during the time of EUS-LB as compared with 19-gauge needle.&#xD;
&#xD;
      6 STUDY DESIGN 6.1 Description This is a prospective trial comparing the biopsy specimen&#xD;
      adequacy of 19 versus 22-gauge core needle for EUS-LB.&#xD;
&#xD;
      6 6.3 Recruitment Patients shall be recruited in the pre-procedural endoscopy area. After&#xD;
      identifying subjects, a study investigator shall discuss the study in detail either in person&#xD;
      (at which point the patient will read the consent form). A second individual will witness the&#xD;
      consent.&#xD;
&#xD;
      6.4 Study Duration 6.4.1 Approximate Duration of Subject Participation Participation in this&#xD;
      study is until 1 week post-procedure. 6.4.2 Approximate Duration of Study The duration of the&#xD;
      study shall last until 6 months from enrollment of the last study participant. This shall&#xD;
      allow for analysis of final data points and construction of a manuscript.&#xD;
&#xD;
      6.5 Procedures Epic electronic health records database will allow for availability of&#xD;
      demographic data and office-based follow-up records. Provation MD software information will&#xD;
      provide details regarding endoscopic parameters and intervention performed.&#xD;
&#xD;
      Electronic records gathered for study purposes will only be available to study investigators&#xD;
      and will be stored on an encrypted hard drive on a computer. Data will initially be entered&#xD;
      with protected health information (PHI) attached so that all information can be obtained.&#xD;
      Once all data collection is complete identifiers will be removed and random number assigned&#xD;
      to the patients.&#xD;
&#xD;
      Paper copies of study questionnaires will be filled out in the endoscopy center and stored in&#xD;
      a locked cabinet in the endoscopy center workroom. The door to the workroom with the cabinet&#xD;
      is locked after hours and the endoscopy center is locked after hours as well.&#xD;
&#xD;
      Upon initial encounter, the study shall be described to the patient in detail by one of the&#xD;
      study investigators and informed consent obtained.&#xD;
&#xD;
      Once the patients has agreed to participate, demographic data will be obtained including;&#xD;
      age, gender, height [inches (in)], weight [pounds (lb)], body mass index (BMI)(lb/in2), past&#xD;
      medical history [in particular diagnosis of liver disease, biliary or pancreatic disease,&#xD;
      ascites, encephalopathy, portal hypertension, portal hypertension-related bleeding (ie.&#xD;
      varices), liver cancer or masses]. Past surgical history shall be obtained regarding prior&#xD;
      cholecystectomy, hepatobiliary or pancreatic surgery (i.e. pancreaticojejunostomy) or&#xD;
      bariatric surgery (ie. Roux-en-Y gastric bypass). Medication and social history shall be&#xD;
      performed regarding alcohol intake per week and hepatotoxic medications (i.e. acetaminophen).&#xD;
      A baseline INR and platelet count shall be performed on all individuals prior to EUS-LB, as&#xD;
      is the standard of care.&#xD;
&#xD;
      EUS-LB Protocol&#xD;
&#xD;
      Patients undergoing EUS-LB receive sedation prior to the procedure, as per normal practice.&#xD;
      This is provided by a certified registered nurse anesthetist (CRNA). The endosonographic&#xD;
      study will be conducted with a linear array echoendoscope (GF-UC140-AL5; Olympus America,&#xD;
      Center Valley, PA). Before needle puncture of the desired lobe, color Doppler imaging will be&#xD;
      used to ensure the lack of vascular structures in the trajectory of the needle. The EUS-LB&#xD;
      will be performed in widely separated regions of the liver using a 19-gauge EUS-FNA (fine&#xD;
      needle aspiration) needle (Expect Flexible 19g, Boston Scientific, Marlborough, MA) and a&#xD;
      22-gauge FNB needle (SharkCore, Beacon Endoscopic, Sunnyvale, CA, or Acquire 22g, Boston&#xD;
      Scientific, Marlborough, MA). A computer-generated randomized schema shall determine initial&#xD;
      needle gauge selection.&#xD;
&#xD;
      The left lobe is described as liver parenchyma identified a few centimeters below the&#xD;
      gastroesophageal junction with the echoendoscope torqued clockwise. The right lobe is&#xD;
      consider the large area of liver tissue can be seen through the duodenal bulb, near the&#xD;
      gallbladder. The stylet is removed, heparin flushed through the needle lumen, and the suction&#xD;
      device set and attached to the needle hub. The prepared needle is then inserted into the&#xD;
      echoendoscope, A transgastric approach will be used to obtain samples from the left lobe of&#xD;
      the liver; a transduodenal approach, with the linear echoendoscope positioned in the duodenal&#xD;
      bulb, will be used to obtain samples from the large amount of liver parenchyma seen in that&#xD;
      location. Once adequate liver parenchymal penetration will be achieved with the needle (∼2-6&#xD;
      cm), full suction will be applied with a 20-mL vacuum syringe. One pass consists of a total&#xD;
      of 7 to 10 to-and-fro needle motions with the fanning technique applied under direct and&#xD;
      continuous endosonographic visualization of the tip of the needle.&#xD;
&#xD;
      The needle will then be removed from the echoendoscope. The specimen will be pushed from the&#xD;
      needle with the stylet directly into a microsieve, and blood washed from the specimen with a&#xD;
      gentle saline rinse. The endosonographer looks for multiple pieces of light brown tissue&#xD;
      approximately 5 to 15 mm in length. The tissue cores are then &quot;floated&quot; off the microsieve&#xD;
      into formalin solution. Then, a second pass will be made from the same region of the liver&#xD;
      using the alternate needle used from the first pass. Heparin is flushed through the needle&#xD;
      lumen prior to the next pass. The biopsy process is then repeated on the opposite liver lobe.&#xD;
      Two passes per liver lobe are made; one with the standard 19g EUS-FNA needle, and one with&#xD;
      the 22g EUS core needle. All patients are closely observed in the recovery area for 1 hour&#xD;
      after the procedure, as per our standard policy. Patients will be followed-up with by a phone&#xD;
      call the next day and at 1 week after the procedure.&#xD;
&#xD;
      Sample Processing The surgical pathology department, per a specific protocol for clinical&#xD;
      practice, will process the EUS-LB samples. Tissue samples are left in formalin for at least 1&#xD;
      hour before processing. The contents of the formalin jar will be poured into a petri dish,&#xD;
      and visible cores of liver tissue picked out with small forceps by the surgical pathology&#xD;
      technician. These pieces are arranged in a linear fashion on lens paper, then the specimen&#xD;
      photographed alongside a ruler to estimates pre-processing tissue lengths. Samples from both&#xD;
      lobes and the different needles will be submitted for evaluation separately. The tissue will&#xD;
      be processed in standard fashion, and slide blanks made (5-μm tissue thickness). These blanks&#xD;
      are stained with hematoxylin and eosin, trichrome, and reticulin, with other special stains&#xD;
      done as needed. The slides is digitized using a whole slide scanner (ScanScope CS; Aperio&#xD;
      Technologies, Inc, Vista, CA), and the digitized images used for quantitative analysis&#xD;
      (eSlide Manager; Aperio Technologies, Inc). Quantification of sample length (mm) and portal&#xD;
      triads is performed by 2 of the investigators, annotating the digital images with the&#xD;
      software. Fellowship-trained GI pathologists then perform histologic interpretation for&#xD;
      clinical use.&#xD;
&#xD;
      Post-Procedural Follow-up After undergoing the procedure, patients will receive a 1week&#xD;
      follow-up phone call to monitor for adverse events (i.e. bleeding).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>N/A</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>Diagnostic</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Specimens for Which a Histologic Diagnosis Could be Made Based Upon the Amount of Tissue Obtained With the Needle</measure>
    <time_frame>7 days</time_frame>
    <description>Defined by total portal structures &gt; 5 or length of the longest piece &gt; 15 mm) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Number of Specimens With a Visible Core After Needle Biopsy</measure>
    <time_frame>Day of Procedure</time_frame>
    <description>Presence of a visible core specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Specimens With a Visible Clot After Needle Biopsy</measure>
    <time_frame>Day of Procedure</time_frame>
    <description>Presence of visible clots in specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Patients With Visible Bleeding After Needle Biopsy</measure>
    <time_frame>7 days</time_frame>
    <description>Patient with blood visible from patient's mouth, rectum with a 2 gram drop in hemoglobin Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Patients With Pain 1 Day After Needle Biopsy</measure>
    <time_frame>1 days</time_frame>
    <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Patients With Pain 7 Day After Needle Biopsy</measure>
    <time_frame>7 days</time_frame>
    <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Patients Requiring Medical Care After Needle Biopsy</measure>
    <time_frame>7 Days</time_frame>
    <description>Patient requiring visit to healthcare center (emergency room, hospital, call to service) within time 7 days Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Portal Tracts (PT) in the Specimen (Total) Under Histologic Examination</measure>
    <time_frame>7 days</time_frame>
    <description>Number of portal tracts (PT) in the specimen (total) under histologic examination Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregate Specimen Length Under Histologic Examination</measure>
    <time_frame>7 days</time_frame>
    <description>Length of all the tissue (centimeters) by adding the sum of all pieces Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of the Longest Piece Under Histologic Examination</measure>
    <time_frame>7 days</time_frame>
    <description>length of the longest tissue biopsy piece (centimeters) as measured by pathology Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Diagnoses Diseases</condition>
  <condition>Ultrasound Therapy; Complications</condition>
  <condition>Liver Diseases</condition>
  <arm_group>
    <arm_group_label>19 Left</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe</description>
  </arm_group>
  <arm_group>
    <arm_group_label>22 Left</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe</description>
  </arm_group>
  <arm_group>
    <arm_group_label>19 Right</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EUS-guided liver biopsy using a 19-gauge liver biopsy in the right lobe</description>
  </arm_group>
  <arm_group>
    <arm_group_label>22 Right</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the right lobe</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EUS-guided liver biopsy</intervention_name>
    <description>Endoscopic ultrasound guided liver biopsy</description>
    <arm_group_label>19 Left</arm_group_label>
    <arm_group_label>19 Right</arm_group_label>
    <arm_group_label>22 Left</arm_group_label>
    <arm_group_label>22 Right</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients undergoing EUS-LB&#xD;
&#xD;
          2. Platelet count &gt; 50,000&#xD;
&#xD;
          3. International normalized ratio (INR) &lt; 1.5&#xD;
&#xD;
          4. Age &gt; 18 years&#xD;
&#xD;
          5. Non-pregnant patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 years&#xD;
&#xD;
          2. Pregnant Patients&#xD;
&#xD;
          3. Inability to obtain consent&#xD;
&#xD;
          4. Anticoagulants or anti-platelet agents use (excluding aspirin) within the last 7-10&#xD;
             days&#xD;
&#xD;
          5. Platelet count &lt; 50,000&#xD;
&#xD;
          6. INR &gt; 1.5&#xD;
&#xD;
          7. Presence of ascites&#xD;
&#xD;
          8. Known liver cirrhosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David L Diehl, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Geisinger Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>June 2019</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>March 20, 2019</results_first_submitted>
  <results_first_submitted_qc>October 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2019</results_first_posted>
  <last_update_submitted>October 17, 2019</last_update_submitted>
  <last_update_submitted_qc>October 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EUS</keyword>
  <keyword>Biopsy</keyword>
  <keyword>Liver</keyword>
  <keyword>FNA</keyword>
  <keyword>FNB</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</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>August 29, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02967991/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 29, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02967991/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 6, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02967991/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>19G EUS-FNA Needle First, Then 22G FNB Needle</title>
          <description>EUS-guided liver biopsy&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy&#xD;
First Intervention: 10 minutes Washout: 1 minute Second Intervention: 10 minutes</description>
        </group>
        <group group_id="P2">
          <title>22G FNB Needle First, Then 19G EUS-FNA Needle</title>
          <description>EUS-guided liver biopsy&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy&#xD;
First Intervention: 10 minutes Washout: 1 minute Second Intervention: 10 minutes</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">First Intervention: 10 minutes Washout: 1 minute Second Intervention: 10 minutes</participants>
                <participants group_id="P2" count="10">First Intervention: 10 minutes Washout: 1 minute Second Intervention: 10 minutes</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Total</title>
          <description>EUS-guided liver biopsy using a 19-gauge FNA then 22-gauge liver biopsy needle&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>mean years total population</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.5" spread="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Sex of Particpants : Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sex of Particpants : Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Specimens for Which a Histologic Diagnosis Could be Made Based Upon the Amount of Tissue Obtained With the Needle</title>
        <description>Defined by total portal structures &gt; 5 or length of the longest piece &gt; 15 mm) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <population>specimens not particpants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNB-fine needle biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Specimens for Which a Histologic Diagnosis Could be Made Based Upon the Amount of Tissue Obtained With the Needle</title>
          <description>Defined by total portal structures &gt; 5 or length of the longest piece &gt; 15 mm) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not particpants</population>
          <units>specimens</units>
          <param>Number</param>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Specimens With a Visible Core After Needle Biopsy</title>
        <description>Presence of a visible core specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>Day of Procedure</time_frame>
        <population>specimens not particpants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNB-fine needle biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Specimens With a Visible Core After Needle Biopsy</title>
          <description>Presence of a visible core specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not particpants</population>
          <units>specimens</units>
          <param>Number</param>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Specimens With a Visible Clot After Needle Biopsy</title>
        <description>Presence of visible clots in specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>Day of Procedure</time_frame>
        <population>specimens not participants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNB-fine needle biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Specimens With a Visible Clot After Needle Biopsy</title>
          <description>Presence of visible clots in specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not participants</population>
          <units>specimens</units>
          <param>Number</param>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Patients With Visible Bleeding After Needle Biopsy</title>
        <description>Patient with blood visible from patient's mouth, rectum with a 2 gram drop in hemoglobin Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Total Population</title>
            <description>Adverse event evaluating the total population</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Patients With Visible Bleeding After Needle Biopsy</title>
          <description>Patient with blood visible from patient's mouth, rectum with a 2 gram drop in hemoglobin Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Patients With Pain 1 Day After Needle Biopsy</title>
        <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>1 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Total Population</title>
            <description>Adverse events evaluating the total population</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Patients With Pain 1 Day After Needle Biopsy</title>
          <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Patients With Pain 7 Day After Needle Biopsy</title>
        <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Total Population</title>
            <description>adverse event evaluating the total population</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Patients With Pain 7 Day After Needle Biopsy</title>
          <description>Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Patients Requiring Medical Care After Needle Biopsy</title>
        <description>Patient requiring visit to healthcare center (emergency room, hospital, call to service) within time 7 days Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Total Population</title>
            <description>Adverse event evaluating the total population</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Patients Requiring Medical Care After Needle Biopsy</title>
          <description>Patient requiring visit to healthcare center (emergency room, hospital, call to service) within time 7 days Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Portal Tracts (PT) in the Specimen (Total) Under Histologic Examination</title>
        <description>Number of portal tracts (PT) in the specimen (total) under histologic examination Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <population>specimens not participants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Portal Tracts (PT) in the Specimen (Total) Under Histologic Examination</title>
          <description>Number of portal tracts (PT) in the specimen (total) under histologic examination Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not participants</population>
          <units>mean portal tracts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="5.9"/>
                    <measurement group_id="O2" value="6.1" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aggregate Specimen Length Under Histologic Examination</title>
        <description>Length of all the tissue (centimeters) by adding the sum of all pieces Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <population>specimens not participants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNB-fine needle biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Aggregate Specimen Length Under Histologic Examination</title>
          <description>Length of all the tissue (centimeters) by adding the sum of all pieces Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not participants</population>
          <units>cm for portal tracts of specimens</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.5" spread="35.4"/>
                    <measurement group_id="O2" value="66.9" spread="47.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of the Longest Piece Under Histologic Examination</title>
        <description>length of the longest tissue biopsy piece (centimeters) as measured by pathology Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
        <time_frame>7 days</time_frame>
        <population>specimens not participants</population>
        <group_list>
          <group group_id="O1">
            <title>19 Gauge FNA</title>
            <description>EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNA-fine needle aspiration</description>
          </group>
          <group group_id="O2">
            <title>22 Gauge FNB</title>
            <description>EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy FNB-fine needle biopsy</description>
          </group>
        </group_list>
        <measure>
          <title>Length of the Longest Piece Under Histologic Examination</title>
          <description>length of the longest tissue biopsy piece (centimeters) as measured by pathology Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.&#xD;
FNA-fine needle aspiration FNB-fine needle biopsy</description>
          <population>specimens not participants</population>
          <units>mean cm for portal tracts of specimens</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>specimens</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>specimens</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.2" spread="5.1"/>
                    <measurement group_id="O2" value="10.8" spread="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Total Population</title>
          <description>EUS-guided liver biopsy using 19 g needle and 22 g needle in a cross-over design. Results were evaluated for groups undergoing 19 g needle followed by 22 g needle and 22 g needle followed by 19 g needle.&#xD;
EUS-guided liver biopsy: Endoscopic ultrasound guided liver biopsy&#xD;
NOTE that as this is a cross-over design adverse events were reported occurred were reported on a per-patient basis. Given that events were reported after the procedure, unique to each patient, and cannot be expressed based upon a per-intervention basis as both interventions were performed on each patient and only one patient can have one unique intervention which is impossible to determine the route-source intervention as the culprit due to cross-over design same session.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="20"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>No blinding, single-center, no generalization to community, carrier effect with cross-over design, obesity, second pass.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Shaffer Mok</name_or_title>
      <organization>University Hospitals Case Western Reserve</organization>
      <phone>4404065500</phone>
      <email>Shaffer.Mok@UHHospitals.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/NCT02967991
org study id: 2016-0281
nct id: NCT02967991
lead sponsor: 
has dmc: Yes
Chronic liver disorders (CLD) are a major cause of morbidity and mortality for individuals in
      the US. Though serologic analysis will often lead to a conclusive diagnosis, liver biopsy
      remains an important method for helping to determine the etiology and stage of LD.
      Percutaneous liver biopsy (PLB), transjugular liver biopsy (TLB) and surgical liver biopsy
      (SLB) are alternative methods for obtaining hepatic tissue. In recent years endoscopic
      ultrasound guided-liver biopsy (EUS-LB) has come to the forefront as a safe and effective
      method for obtaining tissue in CLD. There are several studies of the safety of EUS-LB as well
      as the adequacy of specimens obtained in this fashion. Most studies involve a 19-gauge
      needle, therefore in this study the investigators hope to compare the tissue yields of a
      22-gauge fine needle biopsy (FNB) needle, in comparison to conventional 19-gauge. The
      investigators predict that 19 and 22 gauge FNB needle will demonstrate similar diagnostic
      accuracy, with less visible blood artifact. Similarly the investigators predict the safety to
      be equal.
3 BACKGROUND AND SIGNIFICANCE Chronic liver disease has a number of causes, and leads to
      significant mortality and morbidity in the United States. It has been estimated that roughly
      36,000 individuals die annually from the burden of chronic liver disease, thus early
      diagnosis and intervention are paramount to preventing such complications. Though serologic
      markers and non-invasive diagnostic imaging modalities are used as a method for determining
      the underlying disease process, these methods lack the specificity of determining etiology of
      a patient's chronic liver disease. Therefore, liver biopsy remains the "gold standard" for
      obtaining valuable diagnostic and prognostic information.

      At present there exist several methods for liver tissue acquisition. The most widely accepted
      method remains percutaneous route (PLB), which utilizes percussion or imaging to localization
      the biopsy site. The issue with this approach is its potential complication of
      post-procedural pain in up to 84%, bleeding in 1/2500-10,000 procedures, with under 1/10,000
      of these cases being fatal. Another means for obtaining tissue samples is the transjugular
      route (TLB), which also allows for portal pressure measurement, and is usually reserved for
      patients with coagulopathy.

      More recently, endoscopic ultrasound guided liver biopsy (EUS-LB) has been developed as a
      newer LB technique. The feasibility of EUS-LB for liver lesions has been validated yielding
      excellent diagnostic results in several studies. This technique has also been evaluated for
      hepatic parenchymal disease with up to 90% diagnostic yield. Subsequently, EUS-LB using a
      19-gauge needle was compared to percutaneous/transjugular routes showing at least
      comparative, and in some instances improved sample acquisition, versus other methods.
      Different 19-gauge needles have been utilized in this setting yielding variable diagnostic
      specimens. However, there has yet to be comparison of 19 versus a 22-gauge core biopsy needle
      for EUS-LB. The safety profile with the 19g needle is remarkably good; it seems logical that
      a smaller needle would be at least as good, if not better.

      Primary End Points

        1. Proportion of cases for which a histologic diagnosis could be made based upon the amount
           of tissue obtained with the needle (using total portal structures > 5 or length of the
           longest piece (LLP) > 15 mm).

        2. Number of portal tracts (PT) in the specimen

        3. Aggregate specimen length (ASL), length of the longest piece (LLP), and degree of
           fragmentation Secondary End Points

      1. Presence of a visible core specimen 2. Presence of visible clots in specimen 3. Adverse
      events (AE) and serious adverse events (SAE) 4 HYPOTHESIS AND SPECIFIC aims

      4.1 Hypothesis The investigators predict that the 19-gauge needle and 22-gauge core needle
      will have similar ability to obtain adequate EUS-LB specimens 4.2 Specific Aim 1 To determine
      the adequacy of EUS-LB using a 22-gauge core needle as compared with 19-gauge needle 4.3
      Specific Aim 2 To determine if the 22-gauge core needle will demonstrate less blood artifact
      during the time of EUS-LB as compared with 19-gauge needle.

      6 STUDY DESIGN 6.1 Description This is a prospective trial comparing the biopsy specimen
      adequacy of 19 versus 22-gauge core needle for EUS-LB.

      6 6.3 Recruitment Patients shall be recruited in the pre-procedural endoscopy area. After
      identifying subjects, a study investigator shall discuss the study in detail either in person
      (at which point the patient will read the consent form). A second individual will witness the
      consent.

      6.4 Study Duration 6.4.1 Approximate Duration of Subject Participation Participation in this
      study is until 1 week post-procedure. 6.4.2 Approximate Duration of Study The duration of the
      study shall last until 6 months from enrollment of the last study participant. This shall
      allow for analysis of final data points and construction of a manuscript.

      6.5 Procedures Epic electronic health records database will allow for availability of
      demographic data and office-based follow-up records. Provation MD software information will
      provide details regarding endoscopic parameters and intervention performed.

      Electronic records gathered for study purposes will only be available to study investigators
      and will be stored on an encrypted hard drive on a computer. Data will initially be entered
      with protected health information (PHI) attached so that all information can be obtained.
      Once all data collection is complete identifiers will be removed and random number assigned
      to the patients.

      Paper copies of study questionnaires will be filled out in the endoscopy center and stored in
      a locked cabinet in the endoscopy center workroom. The door to the workroom with the cabinet
      is locked after hours and the endoscopy center is locked after hours as well.

      Upon initial encounter, the study shall be described to the patient in detail by one of the
      study investigators and informed consent obtained.

      Once the patients has agreed to participate, demographic data will be obtained including;
      age, gender, height [inches (in)], weight [pounds (lb)], body mass index (BMI)(lb/in2), past
      medical history [in particular diagnosis of liver disease, biliary or pancreatic disease,
      ascites, encephalopathy, portal hypertension, portal hypertension-related bleeding (ie.
      varices), liver cancer or masses]. Past surgical history shall be obtained regarding prior
      cholecystectomy, hepatobiliary or pancreatic surgery (i.e. pancreaticojejunostomy) or
      bariatric surgery (ie. Roux-en-Y gastric bypass). Medication and social history shall be
      performed regarding alcohol intake per week and hepatotoxic medications (i.e. acetaminophen).
      A baseline INR and platelet count shall be performed on all individuals prior to EUS-LB, as
      is the standard of care.

      EUS-LB Protocol

      Patients undergoing EUS-LB receive sedation prior to the procedure, as per normal practice.
      This is provided by a certified registered nurse anesthetist (CRNA). The endosonographic
      study will be conducted with a linear array echoendoscope (GF-UC140-AL5; Olympus America,
      Center Valley, PA). Before needle puncture of the desired lobe, color Doppler imaging will be
      used to ensure the lack of vascular structures in the trajectory of the needle. The EUS-LB
      will be performed in widely separated regions of the liver using a 19-gauge EUS-FNA (fine
      needle aspiration) needle (Expect Flexible 19g, Boston Scientific, Marlborough, MA) and a
      22-gauge FNB needle (SharkCore, Beacon Endoscopic, Sunnyvale, CA, or Acquire 22g, Boston
      Scientific, Marlborough, MA). A computer-generated randomized schema shall determine initial
      needle gauge selection.

      The left lobe is described as liver parenchyma identified a few centimeters below the
      gastroesophageal junction with the echoendoscope torqued clockwise. The right lobe is
      consider the large area of liver tissue can be seen through the duodenal bulb, near the
      gallbladder. The stylet is removed, heparin flushed through the needle lumen, and the suction
      device set and attached to the needle hub. The prepared needle is then inserted into the
      echoendoscope, A transgastric approach will be used to obtain samples from the left lobe of
      the liver; a transduodenal approach, with the linear echoendoscope positioned in the duodenal
      bulb, will be used to obtain samples from the large amount of liver parenchyma seen in that
      location. Once adequate liver parenchymal penetration will be achieved with the needle (∼2-6
      cm), full suction will be applied with a 20-mL vacuum syringe. One pass consists of a total
      of 7 to 10 to-and-fro needle motions with the fanning technique applied under direct and
      continuous endosonographic visualization of the tip of the needle.

      The needle will then be removed from the echoendoscope. The specimen will be pushed from the
      needle with the stylet directly into a microsieve, and blood washed from the specimen with a
      gentle saline rinse. The endosonographer looks for multiple pieces of light brown tissue
      approximately 5 to 15 mm in length. The tissue cores are then "floated" off the microsieve
      into formalin solution. Then, a second pass will be made from the same region of the liver
      using the alternate needle used from the first pass. Heparin is flushed through the needle
      lumen prior to the next pass. The biopsy process is then repeated on the opposite liver lobe.
      Two passes per liver lobe are made; one with the standard 19g EUS-FNA needle, and one with
      the 22g EUS core needle. All patients are closely observed in the recovery area for 1 hour
      after the procedure, as per our standard policy. Patients will be followed-up with by a phone
      call the next day and at 1 week after the procedure.

      Sample Processing The surgical pathology department, per a specific protocol for clinical
      practice, will process the EUS-LB samples. Tissue samples are left in formalin for at least 1
      hour before processing. The contents of the formalin jar will be poured into a petri dish,
      and visible cores of liver tissue picked out with small forceps by the surgical pathology
      technician. These pieces are arranged in a linear fashion on lens paper, then the specimen
      photographed alongside a ruler to estimates pre-processing tissue lengths. Samples from both
      lobes and the different needles will be submitted for evaluation separately. The tissue will
      be processed in standard fashion, and slide blanks made (5-μm tissue thickness). These blanks
      are stained with hematoxylin and eosin, trichrome, and reticulin, with other special stains
      done as needed. The slides is digitized using a whole slide scanner (ScanScope CS; Aperio
      Technologies, Inc, Vista, CA), and the digitized images used for quantitative analysis
      (eSlide Manager; Aperio Technologies, Inc). Quantification of sample length (mm) and portal
      triads is performed by 2 of the investigators, annotating the digital images with the
      software. Fellowship-trained GI pathologists then perform histologic interpretation for
      clinical use.

      Post-Procedural Follow-up After undergoing the procedure, patients will receive a 1week
      follow-up phone call to monitor for adverse events (i.e. bleeding).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: Single (Participant)
measure: Number of Specimens for Which a Histologic Diagnosis Could be Made Based Upon the Amount of Tissue Obtained With the Needle
time frame: 7 days
description: Defined by total portal structures > 5 or length of the longest piece > 15 mm) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Specimens With a Visible Core After Needle Biopsy
time frame: Day of Procedure
description: Presence of a visible core specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Specimens With a Visible Clot After Needle Biopsy
time frame: Day of Procedure
description: Presence of visible clots in specimen (yes/no) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Patients With Visible Bleeding After Needle Biopsy
time frame: 7 days
description: Patient with blood visible from patient's mouth, rectum with a 2 gram drop in hemoglobin Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Patients With Pain 1 Day After Needle Biopsy
time frame: 1 days
description: Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Patients With Pain 7 Day After Needle Biopsy
time frame: 7 days
description: Pain using Likert score 0-10 (10 worst) Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: The Number of Patients Requiring Medical Care After Needle Biopsy
time frame: 7 Days
description: Patient requiring visit to healthcare center (emergency room, hospital, call to service) within time 7 days Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: Number of Portal Tracts (PT) in the Specimen (Total) Under Histologic Examination
time frame: 7 days
description: Number of portal tracts (PT) in the specimen (total) under histologic examination Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: Aggregate Specimen Length Under Histologic Examination
time frame: 7 days
description: Length of all the tissue (centimeters) by adding the sum of all pieces Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
measure: Length of the Longest Piece Under Histologic Examination
time frame: 7 days
description: length of the longest tissue biopsy piece (centimeters) as measured by pathology Subjects underwent a left liver biopsy using a 19-gauge FNA needle, 22-gauge FNB needle, right liver biopsies also using the 19-gauge FNA and 22-gauge FNB.
FNA-fine needle aspiration FNB-fine needle biopsy
arm group label: 19 Left
arm group type: Active Comparator
description: EUS-guided liver biopsy using a19-gauge liver biopsy in the left lobe
arm group label: 22 Left
arm group type: Experimental
description: EUS-guided liver biopsy using a 22-gauge liver biopsy in the left lobe
arm group label: 19 Right
arm group type: Active Comparator
description: EUS-guided liver biopsy using a 19-gauge liver biopsy in the right lobe
arm group label: 22 Right
arm group type: Experimental
description: EUS-guided liver biopsy using a 22-gauge liver biopsy in the right lobe
intervention type: Device
intervention name: EUS-guided liver biopsy
description: Endoscopic ultrasound guided liver biopsy
arm group label: 19 Left
arm group label: 19 Right
arm group label: 22 Left
arm group label: 22 Right
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David L Diehl, M.D.
role: Principal Investigator
affiliation: Geisinger Clinic
facility: 
country: United States
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responsible party type: Sponsor
mesh term: Liver Diseases
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: No blinding, single-center, no generalization to community, carrier effect with cross-over design, obesity, second pass.
point of contact: 