<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/NCT02221934</url>
  </required_header>
  <id_info>
    <org_study_id>003-0001</org_study_id>
    <secondary_id>QUEST Trial</secondary_id>
    <nct_id>NCT02221934</nct_id>
  </id_info>
  <brief_title>Electrical Nerve Block for Amputation Pain</brief_title>
  <official_title>High-Frequency Nerve Block for Post-Amputation Pain: A Pivotal Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neuros Medical, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neuros Medical, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the clinical trial is to learn whether electrical nerve block via the Altius&#xD;
      System is a safe and effective treatment for patients with post-amputation pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Altius System is an implanted device designed to electrically block nerve signals and&#xD;
      alleviate pain. Use of this device may be associated with providing an effective,&#xD;
      mechanism-based yet non-destructive, treatment for managing intractable limb pain in&#xD;
      amputees. In a given patient, the Altius System will be deemed effective if treatment results&#xD;
      in 50% reduction of pain score for more than 50% of all pain episodes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 9, 2014</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline</measure>
    <time_frame>Randomized Testing Window (Month-1 to Month-3 post implant, 2 Month duration)</time_frame>
    <description>Demonstration of 50% reduction in a Numerical Rating Scale (NRS) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events</measure>
    <time_frame>From screening injection visit through 3 months post implant</time_frame>
    <description>Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Pain Relief After 2 Hours</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Average percent change of pain intensity from before treatment, 30 minutes post treatment, and 2 hours post treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Pain Days Per Week</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Average number of pain days compared at Month 3, Month 6 and Month 12 to Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Pain Medication Use</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Average morphine equivalent dose per day over two weeks compared at Month 3, Month 6 and Month 12 to Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Pain Interference to Activities of Daily Living (ADL</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Brief Pain Inventory summary score compared at Month 3, Month 6 and Month 12 to Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Health-related Quality of Life (HR-QOL)</measure>
    <time_frame>12 months post implant</time_frame>
    <description>EQ-5D summary index, SF-12 physical component and mental component summary compared at Month 3, Month 6 and Month 12 to Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Effectiveness: Patient Global Impression of Change (PGIC)</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Comparison of Patient Global Impression of Change across the Month 3, Month 6 and Month 12 office visits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Safety</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Incidence of all Non-Serious Adverse Events, including Non-Serious Adverse Events, Non-Serious Adverse Device Events, and Unanticipated (Non-Serious) Adverse Device Events from the time of consent through 12 months post implant.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory Efficacy: Prosthetic Use</measure>
    <time_frame>12 months post implant</time_frame>
    <description>Average hours of prosthetic use per week averaged across two weeks compared at Month 3, Month 6 and Month 12 to Baseline.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">607</enrollment>
  <condition>Post-Amputation Pain</condition>
  <condition>Phantom Limb Pain</condition>
  <condition>Residual Limb Pain</condition>
  <condition>Stump Pain</condition>
  <arm_group>
    <arm_group_label>Test Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Sham Control Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Altius</intervention_name>
    <description>Electrical signal</description>
    <arm_group_label>Active Sham Control Treatment</arm_group_label>
    <arm_group_label>Test Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 21 years old&#xD;
&#xD;
          -  Unilateral amputated leg ≥ 12 months&#xD;
&#xD;
          -  Chronic post amputation pain ≥ 6 months&#xD;
&#xD;
          -  Pain episodes typically lasting ≥ 60 minutes&#xD;
&#xD;
          -  Stable drug regimen ≥ 4 weeks&#xD;
&#xD;
          -  No changes to medications or prosthesis for 3-month primary study period&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Implanted with an active implantable medical device (i.e. pacemaker)&#xD;
&#xD;
          -  Confounding source of pain that interferes with reporting of limb pain&#xD;
&#xD;
          -  Uncontrolled diabetes&#xD;
&#xD;
          -  Spasticity preventing full range of motion of involved side&#xD;
&#xD;
          -  Extremely short stump; sits on end&#xD;
&#xD;
          -  Untreated psychological condition (i.e. borderline personality)&#xD;
&#xD;
          -  Condition requiring MRI studies or diathermy after device implant&#xD;
&#xD;
          -  Life expectancy of less than 24 months&#xD;
&#xD;
          -  Progressive neurological disease (i.e. multiple sclerosis)&#xD;
&#xD;
          -  Subjects with active local or systemic infection or immunocompromised&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leonardo Kapural, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Clinical Research, Winston-Salem NC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Pain Institute</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences (UAMS)</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HCA Healthcare Research Institute / St. Luke's Presbyterian</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nona Medical Arts</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University / Grady Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Legacy Brain &amp; Spine LLC</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Drug Studies America</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Clinical Research</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Pain Management</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meta Medical Research Institute</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kettering Medical Center</name>
      <address>
        <city>Springboro</city>
        <state>Ohio</state>
        <zip>45066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Surgical and Research Solutions</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardiovascular Surgery Clinic</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Surgical Clinic</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White Research Institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott and White - Temple Memorial Vascular Surgery</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/25655583</url>
    <description>Neuros HFNB Pilot Study - Abstract</description>
  </link>
  <reference>
    <citation>Soin A, Shah NS, Fang ZP. High-frequency electrical nerve block for postamputation pain: a pilot study. Neuromodulation. 2015 Apr;18(3):197-205; discussion 205-6. doi: 10.1111/ner.12266. Epub 2015 Feb 5.</citation>
    <PMID>25655583</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>June 27, 2023</results_first_submitted>
  <results_first_submitted_qc>August 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 11, 2023</results_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pain</keyword>
  <keyword>Chronic</keyword>
  <keyword>Amputation</keyword>
  <keyword>Phantom Pain</keyword>
  <keyword>Stump Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phantom Limb</mesh_term>
  </condition_browse>
  <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>November 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT02221934/Prot_000.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>February 9, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT02221934/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Subjects were required to fulfill all eligibility requirements, including lidocaine injection screening. Eligible subjects underwent study device implant and activation prior to group assignment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Test Treatment</title>
          <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
        </group>
        <group group_id="P2">
          <title>Active Sham Control Treatment</title>
          <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
        </group>
        <group group_id="P3">
          <title>Not Yet Randomized</title>
          <description>Not yet randomized to Test Treatment or Active Sham Control Treatment groups.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Screening</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="607"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="424"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Device Activation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Primary Safety Analysis Cohort</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Successful Implant</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="180"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="178"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Randomized Testing (Month 1 to Month 3)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="87"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Successful Randomization</title>
              <participants_list>
                <participants group_id="P1" count="87"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Successful Device Use (Primary Effectiveness Analysis Cohort)</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
                <participants group_id="P2" count="85"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="82"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Follow-up (Month 3 to Month 12)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="82"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="75"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Test Treatment</title>
          <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
        </group>
        <group group_id="B2">
          <title>Active Sham Control Treatment</title>
          <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="85"/>
            <count group_id="B2" value="85"/>
            <count group_id="B3" value="170"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.1" spread="12.21"/>
                    <measurement group_id="B2" value="57.9" spread="12.57"/>
                    <measurement group_id="B3" value="58.0" spread="12.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="83"/>
                    <measurement group_id="B2" value="84"/>
                    <measurement group_id="B3" value="167"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="71"/>
                    <measurement group_id="B3" value="137"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Level of Amputation</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Above knee (AKA)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Below knee (BKA)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline</title>
        <description>Demonstration of 50% reduction in a Numerical Rating Scale (NRS) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment).</description>
        <time_frame>Randomized Testing Window (Month-1 to Month-3 post implant, 2 Month duration)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Test Treatment</title>
            <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
          </group>
          <group group_id="O2">
            <title>Active Sham Control Treatment</title>
            <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline</title>
          <description>Demonstration of 50% reduction in a Numerical Rating Scale (NRS) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment).</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="85"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>Regression, Logistic</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.176</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.070</ci_lower_limit>
            <ci_upper_limit>0.283</ci_upper_limit>
            <estimate_desc>Difference in Responders between groups presented.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events</title>
        <description>Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events.</description>
        <time_frame>From screening injection visit through 3 months post implant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Test Treatment</title>
            <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
          </group>
          <group group_id="O2">
            <title>Active Sham Control Treatment</title>
            <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events</title>
          <description>Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events.</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="85"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All Serious Adverse Events (SAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Device Effect (SADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unanticipated Adverse Device Effect (UADE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Pain Relief After 2 Hours</title>
        <description>Average percent change of pain intensity from before treatment, 30 minutes post treatment, and 2 hours post treatment</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Pain Days Per Week</title>
        <description>Average number of pain days compared at Month 3, Month 6 and Month 12 to Baseline.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Pain Medication Use</title>
        <description>Average morphine equivalent dose per day over two weeks compared at Month 3, Month 6 and Month 12 to Baseline.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Pain Interference to Activities of Daily Living (ADL</title>
        <description>Brief Pain Inventory summary score compared at Month 3, Month 6 and Month 12 to Baseline.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Health-related Quality of Life (HR-QOL)</title>
        <description>EQ-5D summary index, SF-12 physical component and mental component summary compared at Month 3, Month 6 and Month 12 to Baseline.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Effectiveness: Patient Global Impression of Change (PGIC)</title>
        <description>Comparison of Patient Global Impression of Change across the Month 3, Month 6 and Month 12 office visits</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Safety</title>
        <description>Incidence of all Non-Serious Adverse Events, including Non-Serious Adverse Events, Non-Serious Adverse Device Events, and Unanticipated (Non-Serious) Adverse Device Events from the time of consent through 12 months post implant.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory Efficacy: Prosthetic Use</title>
        <description>Average hours of prosthetic use per week averaged across two weeks compared at Month 3, Month 6 and Month 12 to Baseline.</description>
        <time_frame>12 months post implant</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From time of lidocaine injection screening through Month-12, approximately 1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Test Treatment</title>
          <description>Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.</description>
        </group>
        <group group_id="E2">
          <title>Active Sham Control Treatment</title>
          <description>Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Cardiac tamponade</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Adverse drug reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Implant site necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Medical device discomfort</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Medical device site discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Medical device site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Corona virus infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Implant site cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Implant site infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Incision site abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Rotavirus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Shunt infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Incision site haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Limb traumatic amputation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Tendon injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Calcifying fibrous pseudotumour</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Neuroma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Osteosarcoma metastatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Amputation stump pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Toxic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device extrusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Amputation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Knee operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (21.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="85"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Medical device discomfort</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="85"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Corona virus infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="85"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="85"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="85"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="38" subjects_affected="19" subjects_at_risk="85"/>
                <counts group_id="E2" events="28" subjects_affected="18" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="85"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="85"/>
              </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>
    <point_of_contact>
      <name_or_title>Nick Hargus, PhD. Vice President of Clinical and Medical Affairs</name_or_title>
      <organization>Neuros Medical, Inc.</organization>
      <phone>440-951-2565</phone>
      <email>nhargus@neurosmedical.com</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/NCT02221934
org study id: 003-0001
secondary id: QUEST Trial
nct id: NCT02221934
lead sponsor: 
has dmc: Yes
is fda regulated device: Yes
is unapproved device: Yes
The purpose of the clinical trial is to learn whether electrical nerve block via the Altius
      System is a safe and effective treatment for patients with post-amputation pain.
The Altius System is an implanted device designed to electrically block nerve signals and
      alleviate pain. Use of this device may be associated with providing an effective,
      mechanism-based yet non-destructive, treatment for managing intractable limb pain in
      amputees. In a given patient, the Altius System will be deemed effective if treatment results
      in 50% reduction of pain score for more than 50% of all pain episodes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline
time frame: Randomized Testing Window (Month-1 to Month-3 post implant, 2 Month duration)
description: Demonstration of 50% reduction in a Numerical Rating Scale (NRS) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment).
measure: Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events
time frame: From screening injection visit through 3 months post implant
description: Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events.
measure: Secondary Effectiveness: Pain Relief After 2 Hours
time frame: 12 months post implant
description: Average percent change of pain intensity from before treatment, 30 minutes post treatment, and 2 hours post treatment
measure: Secondary Effectiveness: Pain Days Per Week
time frame: 12 months post implant
description: Average number of pain days compared at Month 3, Month 6 and Month 12 to Baseline.
measure: Secondary Effectiveness: Pain Medication Use
time frame: 12 months post implant
description: Average morphine equivalent dose per day over two weeks compared at Month 3, Month 6 and Month 12 to Baseline.
measure: Secondary Effectiveness: Pain Interference to Activities of Daily Living (ADL
time frame: 12 months post implant
description: Brief Pain Inventory summary score compared at Month 3, Month 6 and Month 12 to Baseline.
measure: Secondary Effectiveness: Health-related Quality of Life (HR-QOL)
time frame: 12 months post implant
description: EQ-5D summary index, SF-12 physical component and mental component summary compared at Month 3, Month 6 and Month 12 to Baseline.
measure: Secondary Effectiveness: Patient Global Impression of Change (PGIC)
time frame: 12 months post implant
description: Comparison of Patient Global Impression of Change across the Month 3, Month 6 and Month 12 office visits
measure: Secondary Safety
time frame: 12 months post implant
description: Incidence of all Non-Serious Adverse Events, including Non-Serious Adverse Events, Non-Serious Adverse Device Events, and Unanticipated (Non-Serious) Adverse Device Events from the time of consent through 12 months post implant.
measure: Exploratory Efficacy: Prosthetic Use
time frame: 12 months post implant
description: Average hours of prosthetic use per week averaged across two weeks compared at Month 3, Month 6 and Month 12 to Baseline.
arm group label: Test Treatment
arm group type: Experimental
description: Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius.
arm group label: Active Sham Control Treatment
arm group type: Active Comparator
description: Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius.
intervention type: Device
intervention name: Altius
description: Electrical signal
arm group label: Active Sham Control Treatment
arm group label: Test Treatment
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Leonardo Kapural, MD, PhD
role: Principal Investigator
affiliation: Center for Clinical Research, Winston-Salem NC
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country: United States
url: https://www.ncbi.nlm.nih.gov/pubmed/25655583
description: Neuros HFNB Pilot Study - Abstract
citation: Soin A, Shah NS, Fang ZP. High-frequency electrical nerve block for postamputation pain: a pilot study. Neuromodulation. 2015 Apr;18(3):197-205; discussion 205-6. doi: 10.1111/ner.12266. Epub 2015 Feb 5.
PMID: 25655583
responsible party type: Sponsor
mesh term: Phantom Limb
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 