<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/NCT03228420</url>
  </required_header>
  <id_info>
    <org_study_id>CA2016-5</org_study_id>
    <nct_id>NCT03228420</nct_id>
  </id_info>
  <brief_title>Comparison of 10 kHz SCS Combined With CMM to CMM Alone in the Treatment of Neuropathic Limb Pain</brief_title>
  <acronym>SENZA-PDN</acronym>
  <official_title>A Post-Market, Multicenter, Prospective, Randomized Clinical Trial Comparing 10 kHz Spinal Cord Stimulation (HF10™ Therapy) Combined With Conventional Medical Management to Conventional Medical Management Alone in the Treatment of Chronic, Intractable, Neuropathic Limb Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nevro Corp</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nevro Corp</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This post-market study is being conducted to document comparative safety, clinical&#xD;
      effectiveness, and cost-effectiveness of the addition of HF10™ therapy to CMM compared with&#xD;
      CMM alone in subjects with chronic, intractable, neuropathic lower limb pain due to diabetic&#xD;
      neuropathy (Painful Diabetic Neuropathy or PDN). This study is a multi-center, prospective,&#xD;
      randomized comparison of the two treatments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Actual">May 1, 2020</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of Safety and Effectiveness</measure>
    <time_frame>3 months</time_frame>
    <description>Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Scores of 3 or Less</measure>
    <time_frame>3 months</time_frame>
    <description>Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Crossover Rates</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder Rates</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remitter Rates</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological Assessment</measure>
    <time_frame>3 months</time_frame>
    <description>Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological Assessment</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related Quality of Life</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin A1c</measure>
    <time_frame>6 months</time_frame>
    <description>Difference between the treatment groups in the average percentage change from baseline in HbA1c levels.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">430</enrollment>
  <condition>Painful Diabetic Neuropathy</condition>
  <arm_group>
    <arm_group_label>HF10 therapy plus CMM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CMM Alone</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Conventional Medical Management</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Senza HF10 Therapy</intervention_name>
    <description>Senza 10kHz Spinal Cord Stimulation</description>
    <arm_group_label>HF10 therapy plus CMM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CMM</intervention_name>
    <description>Conventional Medical Management</description>
    <arm_group_label>CMM Alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have been clinically diagnosed with painful diabetic neuropathy (PDN) of the lower&#xD;
             limbs.&#xD;
&#xD;
          2. Average pain intensity of ≥ 5 out of 10 cm on the VAS in the lower extremities at&#xD;
             enrollment.&#xD;
&#xD;
          3. Have stable neurological status.&#xD;
&#xD;
          4. Be on a stable analgesic regimen.&#xD;
&#xD;
          5. Be 22 years of age or older at the time of enrollment.&#xD;
&#xD;
          6. Be an appropriate candidate for the surgical procedures required in this study.&#xD;
&#xD;
          7. Be capable of subjective evaluation, able to read and understand English-written&#xD;
             questionnaires, and able to read, understand and sign the written informed consent in&#xD;
             English.&#xD;
&#xD;
          8. Be willing and capable of giving informed consent.&#xD;
&#xD;
          9. Be willing and able to comply with study-related requirements, procedures, and&#xD;
             scheduled visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have a diagnosis of a lower limb mononeuropathy, have had a lower limb amputation, or&#xD;
             have large (≥3 cm) and/or gangrenous ulcers of the lower limbs.&#xD;
&#xD;
          2. Have a BMI ≥ 40.&#xD;
&#xD;
          3. Currently prescribed a daily opioid dosage &gt; 120 mg morphine equivalents.&#xD;
&#xD;
          4. Have a medical condition or pain in other area(s), not intended to be treated in this&#xD;
             study.&#xD;
&#xD;
          5. Have a current diagnosis of a progressive neurological disease such a multiple&#xD;
             sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive&#xD;
             arachnoiditis, brain or spinal cord tumor, central deafferentation syndrome, Complex&#xD;
             Regional Pain Syndrome, acute herniating disc, severe spinal stenosis and brachial&#xD;
             plexus injury.&#xD;
&#xD;
          6. Have a current diagnosis or condition such as a coagulation disorder, bleeding&#xD;
             diathesis, platelet dysfunction, low platelet count, severely diminished functional&#xD;
             capacity due to underlying cardiac/pulmonary disease, symptomatic uncontrolled&#xD;
             hypertension, progressive peripheral vascular disease or uncontrolled diabetes&#xD;
             mellitus that presents excess risk for performing the procedure.&#xD;
&#xD;
          7. Have failed prior SCS, dorsal root ganglion (DRG) stimulation, or peripheral nerve&#xD;
             stimulation (PNS) trials for chronic intractable pain.&#xD;
&#xD;
          8. Have significant spinal stenosis, objective evidence of epidural scarring and/or any&#xD;
             signs or symptoms of myelopathy.&#xD;
&#xD;
          9. Any previous history of surgery on the posterior elements (laminectomy, posterior&#xD;
             fusion) resulting in a compromised epidural space.&#xD;
&#xD;
         10. Be benefitting from an interventional procedure and/or surgery to treat lower limb&#xD;
             pain.&#xD;
&#xD;
         11. Have an existing drug pump and/or another active implantable device such as a&#xD;
             pacemaker.&#xD;
&#xD;
         12. Have a condition currently requiring or likely to require the use of diathermy or MRI&#xD;
             that is inconsistent with Senza system guidelines in the Physician's Manual.&#xD;
&#xD;
         13. Have either a metastatic malignant neoplasm or untreated local malignant neoplasm.&#xD;
&#xD;
         14. Have a life expectancy of less than one year.&#xD;
&#xD;
         15. Have a local infection at the anticipated surgical entry site or an active systemic&#xD;
             infection.&#xD;
&#xD;
         16. Be pregnant or plan to become pregnant during the study. Women of childbearing&#xD;
             potential who are sexually active must use a reliable form of birth control, be&#xD;
             surgically sterile, or be at least 2 years post-menopausal.&#xD;
&#xD;
         17. Have within 6 months of enrollment a significant untreated addiction to dependency&#xD;
             producing medications, alcohol or illicit drugs.&#xD;
&#xD;
         18. Be concomitantly participating in another clinical study.&#xD;
&#xD;
         19. Be involved in an injury claim under current litigation.&#xD;
&#xD;
         20. Be a recipient of Social Security Disability Insurance (SSDI).&#xD;
&#xD;
         21. Have a pending or approved worker's compensation claim.&#xD;
&#xD;
         22. Have evidence of an active disruptive psychological or psychiatric disorder or other&#xD;
             known condition significant enough to impact perception of pain, compliance with&#xD;
             intervention and/or ability to evaluate treatment outcome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Caraway, MD</last_name>
    <role>Study Director</role>
    <affiliation>Nevro Corp</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Coastal Orthopedics</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Pain Care</name>
      <address>
        <city>Stockbridge</city>
        <state>Georgia</state>
        <zip>30281</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Pain Management</name>
      <address>
        <city>Greenfield</city>
        <state>Wisconsin</state>
        <zip>53221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <results_first_submitted>July 17, 2021</results_first_submitted>
  <results_first_submitted_qc>July 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 10, 2021</results_first_posted>
  <last_update_submitted>July 17, 2021</last_update_submitted>
  <last_update_submitted_qc>July 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Neuropathies</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>March 19, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT03228420/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>September 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT03228420/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants underwent screening prior to randomization to verify satisfaction of all inclusion/exclusion criteria. Medical records for enrolled participants were evaluated by independent medical monitors for oversight of appropriate patient selection.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>HF10 Therapy Plus CMM</title>
          <description>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management&#xD;
Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation</description>
        </group>
        <group group_id="P2">
          <title>CMM Alone</title>
          <description>Conventional Medical Management&#xD;
CMM: Conventional Medical Management</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="113"/>
                <participants group_id="P2" count="103"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Month-1</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
                <participants group_id="P2" count="101"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Month-3</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized patients</population>
      <group_list>
        <group group_id="B1">
          <title>HF10 Therapy Plus CMM</title>
          <description>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management&#xD;
Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation</description>
        </group>
        <group group_id="B2">
          <title>CMM Alone</title>
          <description>Conventional Medical Management&#xD;
CMM: Conventional Medical Management</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="113"/>
            <count group_id="B2" value="103"/>
            <count group_id="B3" value="216"/>
          </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="60.7" spread="11.4"/>
                    <measurement group_id="B2" value="60.8" spread="9.9"/>
                    <measurement group_id="B3" value="60.8" spread="10.7"/>
                  </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="43"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="136"/>
                  </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="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                    <measurement group_id="B2" value="85"/>
                    <measurement group_id="B3" value="172"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Lower limb pain visual analog scale (VAS) score</title>
          <description>Participants indicate pain severity by marking on a 10 cm line between 0 (no pain) and 10 (worst pain imaginable)</description>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.5" spread="1.6"/>
                    <measurement group_id="B2" value="7.1" spread="1.6"/>
                    <measurement group_id="B3" value="7.3" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Composite of Safety and Effectiveness</title>
        <description>Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).</description>
        <time_frame>3 months</time_frame>
        <population>Intention-to-treat population including all randomized patients whose status could be determined at the 3-month primary assessment, including patients who failed trial SCS and those who withdrew due to an adverse event at any point after the trial SCS phase in the active treatment arm.</population>
        <group_list>
          <group group_id="O1">
            <title>HF10 Therapy Plus CMM</title>
            <description>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management&#xD;
Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation</description>
          </group>
          <group group_id="O2">
            <title>CMM Alone</title>
            <description>Conventional Medical Management&#xD;
CMM: Conventional Medical Management</description>
          </group>
        </group_list>
        <measure>
          <title>Composite of Safety and Effectiveness</title>
          <description>Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).</description>
          <population>Intention-to-treat population including all randomized patients whose status could be determined at the 3-month primary assessment, including patients who failed trial SCS and those who withdrew due to an adverse event at any point after the trial SCS phase in the active treatment arm.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="94"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                    <measurement group_id="O2" value="5"/>
                  </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>&lt;0.001</p_value>
            <p_value_desc>2-sided alpha level of 0.05</p_value_desc>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Scores of 3 or Less</title>
        <description>Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm.</description>
        <time_frame>3 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Crossover Rates</title>
        <description>Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up.</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Rates</title>
        <description>Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Remitter Rates</title>
        <description>Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months).</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neurological Assessment</title>
        <description>Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).</description>
        <time_frame>3 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neurological Assessment</title>
        <description>Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health-related Quality of Life</title>
        <description>Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L).</description>
        <time_frame>6 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hemoglobin A1c</title>
        <description>Difference between the treatment groups in the average percentage change from baseline in HbA1c levels.</description>
        <time_frame>6 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>HF10 Therapy Plus CMM</title>
          <description>The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management&#xD;
Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation</description>
        </group>
        <group group_id="E2">
          <title>CMM Alone</title>
          <description>Conventional Medical Management&#xD;
CMM: Conventional Medical Management</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>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="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="113"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pancreatic mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pancreatitis chronic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pancreatic disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Wound infection staphylococcal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Extradural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paraplegia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Embolic stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </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="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="113"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Hypertensive emergency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="113"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </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="113"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="103"/>
              </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>Initial publication of the results will be a joint, multicenter publication with all PIs and sites contributing data, analyses, and critical review of the manuscript. If no such publication occurs within 12 months of study completion, individual PIs may publish results from their center. PIs will allow sponsor 30 days to review any potential publications or presentations and sponsor can request an additional 60 days if needed.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Donald Middlebrook</name_or_title>
      <organization>Nevro Corp.</organization>
      <phone>(650) 433-2218</phone>
      <email>don.middlebrook@nevro.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/NCT03228420
org study id: CA2016-5
nct id: NCT03228420
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This post-market study is being conducted to document comparative safety, clinical
      effectiveness, and cost-effectiveness of the addition of HF10™ therapy to CMM compared with
      CMM alone in subjects with chronic, intractable, neuropathic lower limb pain due to diabetic
      neuropathy (Painful Diabetic Neuropathy or PDN). This study is a multi-center, prospective,
      randomized comparison of the two treatments.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Composite of Safety and Effectiveness
time frame: 3 months
description: Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).
measure: Pain Scores of 3 or Less
time frame: 3 months
description: Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm.
measure: Crossover Rates
time frame: 6 months
description: Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up.
measure: Responder Rates
time frame: 6 months
description: Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).
measure: Remitter Rates
time frame: 6 months
description: Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months).
measure: Neurological Assessment
time frame: 3 months
description: Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).
measure: Neurological Assessment
time frame: 6 months
description: Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).
measure: Health-related Quality of Life
time frame: 6 months
description: Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L).
measure: Hemoglobin A1c
time frame: 6 months
description: Difference between the treatment groups in the average percentage change from baseline in HbA1c levels.
arm group label: HF10 therapy plus CMM
arm group type: Active Comparator
description: The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management
arm group label: CMM Alone
arm group type: Other
description: Conventional Medical Management
intervention type: Device
intervention name: Senza HF10 Therapy
description: Senza 10kHz Spinal Cord Stimulation
arm group label: HF10 therapy plus CMM
intervention type: Other
intervention name: CMM
description: Conventional Medical Management
arm group label: CMM Alone
criteria: 
gender: All
minimum age: 22 Years
maximum age: N/A
healthy volunteers: No
last name: David Caraway, MD
role: Study Director
affiliation: Nevro Corp
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetic Neuropathies
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 