<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/NCT03276975</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00083991</org_study_id>
    <nct_id>NCT03276975</nct_id>
  </id_info>
  <brief_title>A Randomized Trial of CT Fluoroscopy-guided Targeted Autologous Blood and Fibrin Glue Patching for Treatment</brief_title>
  <official_title>A Randomized Trial of CT Fluoroscopy-guided Targeted Autologous Blood and Fibrin Glue Patching for Treatment of Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this randomized controlled trial (RCT) is to compare the efficacy of CT&#xD;
      fluoroscopy-guided targeted epidural patching for treatment of imaging-confirmed spinal CSF&#xD;
      leaks to that of a simulated procedure without patching material in patients with spontaneous&#xD;
      intracranial hypotension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Spontaneous intracranial hypotension (SIH) is a condition caused by non-iatrogenic spinal CSF&#xD;
      leaks that classically presents with orthostatic headaches. These headaches, in conjunction&#xD;
      with other presenting symptoms such as nausea, diplopia, tinnitus, and cognitive deficits,&#xD;
      often result in profound disability. SIH is considerably underreported due to pervasive&#xD;
      misdiagnosis. Thus, while the estimated annual incidence is reported to be 5 in 100,000, the&#xD;
      actual number is likely considerably greater.&#xD;
&#xD;
      The current standard-of-care treatment for SIH cases that are refractory to conservative&#xD;
      measures (i.e. bed rest and hydration) is percutaneous epidural blood patching (EBP) of the&#xD;
      spinal CSF leak. Percutaneous EBP can be performed in several ways: 1) with or without&#xD;
      imaging guidance, 2) targeted to a site of known or suspected CSF leak or non-targeted, and&#xD;
      3) with or without the addition of fibrin glue sealant.&#xD;
&#xD;
      The leading theory for the mechanism behind percutaneous EBP treatment of SIH is that it&#xD;
      creates a durable seal of the CSF leak resulting in normalization of CSF hydrodynamics and a&#xD;
      resultant diminution in symptoms. Fibrin glue, a sealant used for treatment of unintended&#xD;
      durotomies during neurosurgery, is thought to improve the likelihood of a successful patch&#xD;
      over patches containing blood alone. Therefore, imaging-guided targeted delivery of patching&#xD;
      material containing both blood and fibrin glue directly to the site of CSF leak, a novel&#xD;
      therapy, is presumed to be the optimal therapy. For this reason, this procedure has become&#xD;
      standard-of-care at many tertiary-care institutions over the past several years.&#xD;
&#xD;
      Our group has extensive experience with CT fluoroscopy-guided targeted blood and fibrin glue&#xD;
      patching of proven CSF leaks in SIH patients. However, significant uncertainty remains with&#xD;
      regard to the efficacy of this procedure due to a paucity of outcomes data and the absence of&#xD;
      any prospective RCTs. In fact, nearly all of the current evidence for the treatment of SIH is&#xD;
      found in the form of retrospective chart reviews. Given the growing recognition of SIH, the&#xD;
      fact that a known subset of patients will have spontaneous resolution of symptoms, and the&#xD;
      absence of clear evidence to guide treatment, there is a critical need to evaluate the&#xD;
      efficacy of targeted patching with blood and fibrin glue with a prospective RCT. Fulfilling&#xD;
      this unmet need forms the basis for this proposal. While determining the efficacy of the&#xD;
      other types of EBPs is also important, we aim to begin by evaluating the efficacy of the&#xD;
      presumed optimal therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2017</start_date>
  <completion_date type="Actual">March 19, 2020</completion_date>
  <primary_completion_date type="Actual">March 19, 2020</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline</measure>
    <time_frame>Baseline, 1 month</time_frame>
    <description>Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Median HIT-6 Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 4 months</time_frame>
    <description>Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
    <description>The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Median NRS Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
    <description>The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 (&quot;no pain&quot;) to 10 (&quot;worst possible pain&quot;). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
    <description>The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
    <description>The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PGIC (Patient Global Impression of Change) Score From Baseline</measure>
    <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
    <description>PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Cerebrospinal Fluid Leaks</condition>
  <arm_group>
    <arm_group_label>Patching of CSF Leaks with Autologous Blood and Fibrin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CT fluoroscopy-guided blood and fibrin glue patching targeted to the site of CSF leak.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Simulated Patching Procedure</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Instead of injection of blood and fibrin glue patching material through the needles, an equivalent volume of preservative free sterile Elliots B solution will be injected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TISSEEL</intervention_name>
    <description>TISSEEL is a fibrin sealant indicated for use as an adjunct to hemostasis in adult and pediatric patients (&gt;1 month of age) undergoing surgery when control of bleeding by conventional surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. TISSEEL is effective in heparinized patients</description>
    <arm_group_label>Patching of CSF Leaks with Autologous Blood and Fibrin</arm_group_label>
    <arm_group_label>Simulated Patching Procedure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients meeting International Classification of Headache Disorders 3rd Edition&#xD;
             (ICHD-3) criteria for a diagnosis of SIH (Table 1) who have had a contrast-enhanced&#xD;
             brain MRI and a myelogram confirming the presence of a CSF leak will be recruited from&#xD;
             the Duke Radiology spine intervention clinic [25]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  recent (i.e., &lt; 2 weeks) blood patch&#xD;
&#xD;
          -  contraindication or inability to undergo the procedure&#xD;
&#xD;
          -  inability to provide informed consent&#xD;
&#xD;
          -  expected inability to complete follow-up assessment&#xD;
&#xD;
          -  a contraindication to receiving contrast material (precluding an epidurogram)&#xD;
&#xD;
          -  contraindication to receiving fibrin glue (i.e., allergy).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <results_first_submitted>March 17, 2021</results_first_submitted>
  <results_first_submitted_qc>May 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2021</results_first_posted>
  <last_update_submitted>May 26, 2021</last_update_submitted>
  <last_update_submitted_qc>May 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CT fluoroscopy</keyword>
  <keyword>epidural patching</keyword>
  <keyword>spontaneous intracranial hypotension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebrospinal Fluid Leak</mesh_term>
    <mesh_term>Intracranial Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrin Tissue Adhesive</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03276975/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
          <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
        </group>
        <group group_id="P2">
          <title>Simulated Patching Procedure</title>
          <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Crossover At 2 Months</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
          <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
        </group>
        <group group_id="B2">
          <title>Simulated Patching Procedure</title>
          <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</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="8"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="46.0" spread="13.1"/>
                    <measurement group_id="B2" value="57.6" spread="14.7"/>
                    <measurement group_id="B3" value="51.8" spread="13.9"/>
                  </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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline</title>
        <description>Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
        <time_frame>Baseline, 1 month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline</title>
          <description>Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12" lower_limit="-16" upper_limit="-7"/>
                    <measurement group_id="O2" value="-7" lower_limit="-13" upper_limit="-1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Median HIT-6 Score From Baseline</title>
        <description>Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
        <time_frame>Baseline, 2 weeks, 4 months</time_frame>
        <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median HIT-6 Score From Baseline</title>
          <description>Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: &quot;never&quot;, &quot;rarely&quot;, &quot;sometimes&quot;, &quot;very often&quot;, or &quot;always&quot;. These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.</description>
          <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.5" lower_limit="-10" upper_limit="0.5"/>
                    <measurement group_id="O2" value="-7" lower_limit="-17" upper_limit="-3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.5" lower_limit="-16.5" upper_limit="-1.5"/>
                    <measurement group_id="O2" value="-12" lower_limit="-24" upper_limit="-7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline</title>
        <description>The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270</description>
        <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
        <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline</title>
          <description>The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270</description>
          <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25" lower_limit="-55" upper_limit="6"/>
                    <measurement group_id="O2" value="16" lower_limit="-35" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-62.5" lower_limit="-117" upper_limit="-37"/>
                    <measurement group_id="O2" value="-40" lower_limit="-86" upper_limit="-3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-87" lower_limit="-134.5" upper_limit="-69.5"/>
                    <measurement group_id="O2" value="-53" lower_limit="-210" upper_limit="-22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Median NRS Score From Baseline</title>
        <description>The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 (&quot;no pain&quot;) to 10 (&quot;worst possible pain&quot;). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.</description>
        <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
        <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median NRS Score From Baseline</title>
          <description>The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 (&quot;no pain&quot;) to 10 (&quot;worst possible pain&quot;). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.</description>
          <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-1.5" upper_limit="1"/>
                    <measurement group_id="O2" value="-1" lower_limit="-3" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" lower_limit="-4.5" upper_limit="-1"/>
                    <measurement group_id="O2" value="0" lower_limit="-3" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" lower_limit="-5" upper_limit="-0.5"/>
                    <measurement group_id="O2" value="-2" lower_limit="-3" upper_limit="-1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline</title>
        <description>The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.</description>
        <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
        <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline</title>
          <description>The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.</description>
          <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="0" upper_limit="0.2"/>
                    <measurement group_id="O2" value="0.1" lower_limit="-0.1" upper_limit="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0.4"/>
                    <measurement group_id="O2" value="0.1" lower_limit="0" upper_limit="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="-0.1" upper_limit="0.1"/>
                    <measurement group_id="O2" value="0.2" lower_limit="0.1" upper_limit="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline</title>
        <description>The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.</description>
        <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
        <population>Patients were only analyzed with respect to WPAI if they were currently employed at the time of the outcome measure acquisition (for each time point). Thus, there were fewer patients for whom data was recorded than were enrolled in each arm (number analyzed).&#xD;
All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline</title>
          <description>The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.</description>
          <population>Patients were only analyzed with respect to WPAI if they were currently employed at the time of the outcome measure acquisition (for each time point). Thus, there were fewer patients for whom data was recorded than were enrolled in each arm (number analyzed).&#xD;
All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="-16.9" upper_limit="13.5"/>
                    <measurement group_id="O2" value="-0.3" lower_limit="-8.8" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 month</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.8" lower_limit="-51" upper_limit="5"/>
                    <measurement group_id="O2" value="-2.3" lower_limit="-20.8" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9" lower_limit="-29" upper_limit="13.7"/>
                    <measurement group_id="O2" value="-28.5" lower_limit="-47" upper_limit="-10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in PGIC (Patient Global Impression of Change) Score From Baseline</title>
        <description>PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.</description>
        <time_frame>Baseline, 2 weeks, 1 month, 4 months</time_frame>
        <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
        <group_list>
          <group group_id="O1">
            <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
            <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
          </group>
          <group group_id="O2">
            <title>Simulated Patching Procedure</title>
            <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in PGIC (Patient Global Impression of Change) Score From Baseline</title>
          <description>PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.</description>
          <population>All patients at the 4 month time point in the Simulated Patching Procedure Arm/Group had crossed over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue Arm/Group</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="3" upper_limit="4.5"/>
                    <measurement group_id="O2" value="2" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="3" upper_limit="5.5"/>
                    <measurement group_id="O2" value="3" lower_limit="1" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="3.5" upper_limit="6"/>
                    <measurement group_id="O2" value="6" lower_limit="2" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected immediately after the initial procedure, immediately after any crossover procedures (performed at the 2-month time point), and also at 1 week after any procedure (initial or crossover).</time_frame>
      <desc>All 7 participants in the Simulated Patching Procedure arm chose to cross over to the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue arm at the 2-month time point. Therefore, a total of 15 participants received the Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue</title>
          <description>CT-fluoroscopic guided epidural patching of the CSF leak or CSF to venous fistula with autologous blood and fibrin glue.</description>
        </group>
        <group group_id="E2">
          <title>Simulated Patching Procedure</title>
          <description>A simulated procedure in which CT fluoroscopy is used to place needles but instead of injection of blood and fibrin glue patching material, an equivalent volume of preservative free sterile saline is injected.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="1" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Rebound Intracranial Hypertension</sub_title>
                <description>Patient experience a headache of new phenotype after the procedure that was self-limited and consistent with rebound intracranial hypertension, a known and expected event after patching procedures.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Asymptomatic self-limited hypertension</sub_title>
                <description>Patient had mild asymptomatic self-limited hypertension while in the recovery room. No untoward effects. Discharged in good condition.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Timothy J. Amrhein, MD</name_or_title>
      <organization>Duke University Medical Center</organization>
      <phone>9196841909</phone>
      <email>timothy.amrhein@duke.edu</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/NCT03276975
org study id: Pro00083991
nct id: NCT03276975
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The goal of this randomized controlled trial (RCT) is to compare the efficacy of CT
      fluoroscopy-guided targeted epidural patching for treatment of imaging-confirmed spinal CSF
      leaks to that of a simulated procedure without patching material in patients with spontaneous
      intracranial hypotension.
Spontaneous intracranial hypotension (SIH) is a condition caused by non-iatrogenic spinal CSF
      leaks that classically presents with orthostatic headaches. These headaches, in conjunction
      with other presenting symptoms such as nausea, diplopia, tinnitus, and cognitive deficits,
      often result in profound disability. SIH is considerably underreported due to pervasive
      misdiagnosis. Thus, while the estimated annual incidence is reported to be 5 in 100,000, the
      actual number is likely considerably greater.

      The current standard-of-care treatment for SIH cases that are refractory to conservative
      measures (i.e. bed rest and hydration) is percutaneous epidural blood patching (EBP) of the
      spinal CSF leak. Percutaneous EBP can be performed in several ways: 1) with or without
      imaging guidance, 2) targeted to a site of known or suspected CSF leak or non-targeted, and
      3) with or without the addition of fibrin glue sealant.

      The leading theory for the mechanism behind percutaneous EBP treatment of SIH is that it
      creates a durable seal of the CSF leak resulting in normalization of CSF hydrodynamics and a
      resultant diminution in symptoms. Fibrin glue, a sealant used for treatment of unintended
      durotomies during neurosurgery, is thought to improve the likelihood of a successful patch
      over patches containing blood alone. Therefore, imaging-guided targeted delivery of patching
      material containing both blood and fibrin glue directly to the site of CSF leak, a novel
      therapy, is presumed to be the optimal therapy. For this reason, this procedure has become
      standard-of-care at many tertiary-care institutions over the past several years.

      Our group has extensive experience with CT fluoroscopy-guided targeted blood and fibrin glue
      patching of proven CSF leaks in SIH patients. However, significant uncertainty remains with
      regard to the efficacy of this procedure due to a paucity of outcomes data and the absence of
      any prospective RCTs. In fact, nearly all of the current evidence for the treatment of SIH is
      found in the form of retrospective chart reviews. Given the growing recognition of SIH, the
      fact that a known subset of patients will have spontaneous resolution of symptoms, and the
      absence of clear evidence to guide treatment, there is a critical need to evaluate the
      efficacy of targeted patching with blood and fibrin glue with a prospective RCT. Fulfilling
      this unmet need forms the basis for this proposal. While determining the efficacy of the
      other types of EBPs is also important, we aim to begin by evaluating the efficacy of the
      presumed optimal therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline
time frame: Baseline, 1 month
description: Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
measure: Change in Median HIT-6 Score From Baseline
time frame: Baseline, 2 weeks, 4 months
description: Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
measure: Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline
time frame: Baseline, 2 weeks, 1 month, 4 months
description: The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270
measure: Change in Median NRS Score From Baseline
time frame: Baseline, 2 weeks, 1 month, 4 months
description: The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 ("no pain") to 10 ("worst possible pain"). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.
measure: Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline
time frame: Baseline, 2 weeks, 1 month, 4 months
description: The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.
measure: Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline
time frame: Baseline, 2 weeks, 1 month, 4 months
description: The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.
measure: Change in PGIC (Patient Global Impression of Change) Score From Baseline
time frame: Baseline, 2 weeks, 1 month, 4 months
description: PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.
arm group label: Patching of CSF Leaks with Autologous Blood and Fibrin
arm group type: Active Comparator
description: CT fluoroscopy-guided blood and fibrin glue patching targeted to the site of CSF leak.
arm group label: Simulated Patching Procedure
arm group type: Placebo Comparator
description: Instead of injection of blood and fibrin glue patching material through the needles, an equivalent volume of preservative free sterile Elliots B solution will be injected.
intervention type: Drug
intervention name: TISSEEL
description: TISSEEL is a fibrin sealant indicated for use as an adjunct to hemostasis in adult and pediatric patients (>1 month of age) undergoing surgery when control of bleeding by conventional surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. TISSEEL is effective in heparinized patients
arm group label: Patching of CSF Leaks with Autologous Blood and Fibrin
arm group label: Simulated Patching Procedure
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cerebrospinal Fluid Leak
mesh term: Intracranial Hypotension
mesh term: Fibrin Tissue Adhesive
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 