<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/NCT03028012</url>
  </required_header>
  <id_info>
    <org_study_id>98370</org_study_id>
    <nct_id>NCT03028012</nct_id>
  </id_info>
  <brief_title>TPI Medication Comparison - Ketorolac, Lidocaine, or Dexamethasone</brief_title>
  <official_title>Double-blind, Prospective Comparison of Medications Used in Trigger Point Injections - Ketorolac, Lidocaine, or Dexamethasone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypothesis&#xD;
&#xD;
      The main hypothesis of this study is that anti-inflammatory medications (ketorolac or&#xD;
      dexamethasone) will provide longer-lasting and greater pain relief than just lidocaine in&#xD;
      trigger point injections where a local twitch response is evoked at the time of the&#xD;
      injection.&#xD;
&#xD;
      Purpose/Specific Aims&#xD;
&#xD;
      The primary objective of this study is to compare the efficacy of three substances used in&#xD;
      TPIs with a LTR identified at the time of the injection: a CS (dexamethasone), a NSAID&#xD;
      (ketorolac), or only a local anesthetic (lidocaine).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Trigger point injections (TPIs) are a commonly-performed procedures by physicians for the&#xD;
      treatment of myofascial pain, specifically targeting myofascial trigger points (MTrPs).&#xD;
      Commonly injected substances include local anesthetic, botulinum toxin, or corticosteroid&#xD;
      (CS), though non-steroidal anti-inflammatory drugs (NSAIDs) and other substances have been&#xD;
      reported. A Cochrane review found that intramuscular injection of local anesthetic&#xD;
      demonstrated moderate evidence of benefit for mechanical neck disorders; no other treatment&#xD;
      demonstrated greater benefit.&#xD;
&#xD;
      Great variation is seen in how TPIs are performed, however. The standard method was described&#xD;
      by Simons and Travell, and is often cited. Hong et al. demonstrated that, similar to the&#xD;
      technique described by Simons and Travell, obtaining a local twitch response (LTR) was the&#xD;
      most important factor in producing pain relief. Further research by Shah et al., which&#xD;
      demonstrated an inflammatory component to MTrPs, also showed a decrease in inflammatory&#xD;
      cytokines following trigger point injections that obtained a LTR. Despite these findings,&#xD;
      most studies do not use the LTR method in their TPI techniques.&#xD;
&#xD;
      Prior studies demonstrated that most patients obtain significant relief from TPI, but did not&#xD;
      identify differences between injection of CS or other substances. However, none of these&#xD;
      studies identified LTRs in their injection techniques.&#xD;
&#xD;
      As can be learned from a review of the published literature on muscular trigger points, the&#xD;
      cause of this condition is unknown, and no single treatment approach has been established as&#xD;
      a clearly accepted gold standard treatment. There is evidence, however, that there is an&#xD;
      inflammatory component associated with trigger points and that obtaining a local twitch&#xD;
      response is associated with a decrease in local inflammation at the site of a trigger point.&#xD;
      The combination of injecting an anti-inflammatory medication and obtaining a local twitch&#xD;
      response has never been studied. The purpose of this study is to examine the comparative&#xD;
      effectiveness of injectable substances on patient outcome after a TPI with LTR identified,&#xD;
      namely a CS (dexamethasone), a NSAID (ketorolac), or only a local anesthetic (lidocaine).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">May 2, 2017</start_date>
  <completion_date type="Actual">May 1, 2019</completion_date>
  <primary_completion_date type="Actual">May 1, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Responder Rate Greater Than 50% on the Numeric Rating Pain Scale (NRS) Improvement</measure>
    <time_frame>Pre-Post Injections Up to Three Months</time_frame>
    <description>Participants in this study underwent TPIs by the following method. The needle was inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. This was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain, one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Numeric Rating Pain Scale (NRS) at Baseline and Three Months.</measure>
    <time_frame>Pre-Injection and Three Month Post Injection(s)</time_frame>
    <description>TPI were treated with a needle inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. Such was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain,one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI) - Modified</measure>
    <time_frame>Baseline and Three Months</time_frame>
    <description>The BPI was evaluated on a scale from 0-10. Zero would mean no interference and 10 would be calculated at complete interferences. We used a 7-point questionnaire about pain. All scores were calculated at baseline and three months.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Myofascial Pain</condition>
  <arm_group>
    <arm_group_label>Ketorolac</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants may be randomized to receive Ketorolac for their TPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lidocaine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants may be randomized to receive Lidocaine for their TPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants may be randomized to receive Dexamethasone for their TPI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketorolac</intervention_name>
    <description>Participants may be randomized to receive Ketorolac for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
    <arm_group_label>Ketorolac</arm_group_label>
    <other_name>Toradol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine</intervention_name>
    <description>Participants may be randomized to receive Lidocaine for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
    <arm_group_label>Lidocaine</arm_group_label>
    <other_name>Xylocaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Participants may be randomized to receive Dexamethasone for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
    <arm_group_label>Dexamethasone</arm_group_label>
    <other_name>Decadron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women age 18 or over&#xD;
&#xD;
          2. At least one active trigger point&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy or contraindication to any NSAID, CS, or local anesthetic&#xD;
&#xD;
          2. Receiving anticoagulant medication&#xD;
&#xD;
          3. History of bleeding disorder&#xD;
&#xD;
          4. Pregnant or breast feeding women&#xD;
&#xD;
          5. Gastrointestinal ulceration&#xD;
&#xD;
          6. Pre-existing renal disease&#xD;
&#xD;
          7. Pre-existing congestive heart failure&#xD;
&#xD;
          8. Diabetes mellitus&#xD;
&#xD;
          9. Prior myocardial infarction or stroke&#xD;
&#xD;
         10. Fibromyalgia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dan Cushman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah Orthopaedic Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  </reference>
  <reference>
    <citation>Simons DG, Travell JG, Simons LS. Travell &amp; Simons' Myofascial Pain and Dysfunction: The Trigger Point Manual. Upper half of body. Vol. 1. Vol 1: Wolters Kluwer Health; 1999.</citation>
  </reference>
  <reference>
    <citation>Drewes AM, Andreasen A, Poulsen LH. Injection Therapy for Treatment of Chronic Myofascial Pain. J Musculoskelet Pain. 2010;1(3-4):289-294.</citation>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>January 14, 2017</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>June 22, 2020</results_first_submitted>
  <results_first_submitted_qc>November 11, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 18, 2020</results_first_posted>
  <last_update_submitted>November 11, 2020</last_update_submitted>
  <last_update_submitted_qc>November 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Daniel Cushman</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Trigger Point Injections</keyword>
  <keyword>steroid</keyword>
  <keyword>nsaid</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Ketorolac</mesh_term>
    <mesh_term>Lidocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <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>April 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT03028012/SAP_003.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT03028012/Prot_ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ketorolac</title>
          <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive 1mL of 1% lidocaine + 1mL of 30mg/mL Ketorolac for their TPI. Participants will be allowed to have subsequent injections, which is standard practice. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="P2">
          <title>Lidocaine</title>
          <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive 2mL of 1% Lidocaine for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="P3">
          <title>Dexamethasone</title>
          <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive 1mL of 1% lidocaine+1mL of 4mg/mL&#xD;
Dexamethasone for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
              </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="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ketorolac</title>
          <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive Ketorolac for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="B2">
          <title>Lidocaine</title>
          <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive Lidocaine for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="B3">
          <title>Dexamethasone</title>
          <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive Dexamethasone for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="B4">
          <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="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="10"/>
          </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54" lower_limit="38" upper_limit="65"/>
                    <measurement group_id="B2" value="40" lower_limit="33" upper_limit="54"/>
                    <measurement group_id="B3" value="47" lower_limit="26" upper_limit="72"/>
                    <measurement group_id="B4" value="48" lower_limit="26" upper_limit="72"/>
                  </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="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White/Caucasion</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Responder Rate Greater Than 50% on the Numeric Rating Pain Scale (NRS) Improvement</title>
        <description>Participants in this study underwent TPIs by the following method. The needle was inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. This was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain, one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
        <time_frame>Pre-Post Injections Up to Three Months</time_frame>
        <population>Participants in other ARM's did not complete survey</population>
        <group_list>
          <group group_id="O1">
            <title>Ketorolac</title>
            <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive 1mL of 1% lidocaine + 1mL of 30mg/mL Ketorolac for their TPI. Participants will be allowed to have subsequent injections, which is standard practice. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O2">
            <title>Lidocaine</title>
            <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive 2mL of 1% Lidocaine for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O3">
            <title>Dexamethasone</title>
            <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive 1mL of 1% lidocaine+1mL of 4mg/mL Dexamethasone for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Responder Rate Greater Than 50% on the Numeric Rating Pain Scale (NRS) Improvement</title>
          <description>Participants in this study underwent TPIs by the following method. The needle was inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. This was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain, one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
          <population>Participants in other ARM's did not complete survey</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="2"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Numeric Rating Pain Scale (NRS) at Baseline and Three Months.</title>
        <description>TPI were treated with a needle inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. Such was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain,one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
        <time_frame>Pre-Injection and Three Month Post Injection(s)</time_frame>
        <population>This study was terminated early due to low enrollment. Zero participants completed the Lidocaine and Dexamethasone arm.</population>
        <group_list>
          <group group_id="O1">
            <title>Ketorolac</title>
            <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive 1mL of 1% lidocaine + 1mL of 30mg/mL Ketorolac for their TPI. Participants will be allowed to have subsequent injections, which is standard practice. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O2">
            <title>Lidocaine</title>
            <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive 2mL of 1% Lidocaine for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O3">
            <title>Dexamethasone</title>
            <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive 1mL of 1% lidocaine+1mL of 4mg/mL Dexamethasone for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
        </group_list>
        <measure>
          <title>Numeric Rating Pain Scale (NRS) at Baseline and Three Months.</title>
          <description>TPI were treated with a needle inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. Such was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain,one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).</description>
          <population>This study was terminated early due to low enrollment. Zero participants completed the Lidocaine and Dexamethasone arm.</population>
          <units>score on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participant Number 3 at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant Number 3 at 3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant Number 8 at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant Number 8 at 3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Pain Inventory (BPI) - Modified</title>
        <description>The BPI was evaluated on a scale from 0-10. Zero would mean no interference and 10 would be calculated at complete interferences. We used a 7-point questionnaire about pain. All scores were calculated at baseline and three months.</description>
        <time_frame>Baseline and Three Months</time_frame>
        <population>Participants in other ARM's did not complete surveys</population>
        <group_list>
          <group group_id="O1">
            <title>Ketorolac</title>
            <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive 1mL of 1% lidocaine + 1mL of 30mg/mL Ketorolac for their TPI. Participants will be allowed to have subsequent injections, which is standard practice. Participants may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O2">
            <title>Lidocaine</title>
            <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive 2mL of 1% Lidocaine for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
          <group group_id="O3">
            <title>Dexamethasone</title>
            <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive 1mL of 1% lidocaine+1mL of 4mg/mL Dexamethasone for their TPI. Participants will be allowed to have subsequent injections, which is standard practice39-43. They may receive up to four injections, spaced at least 1 week apart. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Pain Inventory (BPI) - Modified</title>
          <description>The BPI was evaluated on a scale from 0-10. Zero would mean no interference and 10 would be calculated at complete interferences. We used a 7-point questionnaire about pain. All scores were calculated at baseline and three months.</description>
          <population>Participants in other ARM's did not complete surveys</population>
          <units>score on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participant Number #3 at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant Number #3 at 3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant Number #8 at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant #8 at 3 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected over a 3 month period.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ketorolac</title>
          <description>Participants may be randomized to receive Ketorolac for their TPI.&#xD;
Ketorolac: Participants may be randomized to receive Ketorolac for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="E2">
          <title>Lidocaine</title>
          <description>Participants may be randomized to receive Lidocaine for their TPI.&#xD;
Lidocaine: Participants may be randomized to receive Lidocaine for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</description>
        </group>
        <group group_id="E3">
          <title>Dexamethasone</title>
          <description>Participants may be randomized to receive Dexamethasone for their TPI.&#xD;
Dexamethasone: Participants may be randomized to receive Dexamethasone for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </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>
    <limitations_and_caveats>Early termination of this study due to low subject enrollment, lack of participant follow-up to substantiated end of study measures. There was not enough reported data to provide statistically pertinent or relevant analysis.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Daniel Cushman</name_or_title>
      <organization>University of Utah Physical Medicine and Rehabilitation Orthopedics</organization>
      <phone>8015852373</phone>
      <email>heidi.hansen@hsc.utah.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/NCT03028012
org study id: 98370
nct id: NCT03028012
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Hypothesis

      The main hypothesis of this study is that anti-inflammatory medications (ketorolac or
      dexamethasone) will provide longer-lasting and greater pain relief than just lidocaine in
      trigger point injections where a local twitch response is evoked at the time of the
      injection.

      Purpose/Specific Aims

      The primary objective of this study is to compare the efficacy of three substances used in
      TPIs with a LTR identified at the time of the injection: a CS (dexamethasone), a NSAID
      (ketorolac), or only a local anesthetic (lidocaine).
Background

      Trigger point injections (TPIs) are a commonly-performed procedures by physicians for the
      treatment of myofascial pain, specifically targeting myofascial trigger points (MTrPs).
      Commonly injected substances include local anesthetic, botulinum toxin, or corticosteroid
      (CS), though non-steroidal anti-inflammatory drugs (NSAIDs) and other substances have been
      reported. A Cochrane review found that intramuscular injection of local anesthetic
      demonstrated moderate evidence of benefit for mechanical neck disorders; no other treatment
      demonstrated greater benefit.

      Great variation is seen in how TPIs are performed, however. The standard method was described
      by Simons and Travell, and is often cited. Hong et al. demonstrated that, similar to the
      technique described by Simons and Travell, obtaining a local twitch response (LTR) was the
      most important factor in producing pain relief. Further research by Shah et al., which
      demonstrated an inflammatory component to MTrPs, also showed a decrease in inflammatory
      cytokines following trigger point injections that obtained a LTR. Despite these findings,
      most studies do not use the LTR method in their TPI techniques.

      Prior studies demonstrated that most patients obtain significant relief from TPI, but did not
      identify differences between injection of CS or other substances. However, none of these
      studies identified LTRs in their injection techniques.

      As can be learned from a review of the published literature on muscular trigger points, the
      cause of this condition is unknown, and no single treatment approach has been established as
      a clearly accepted gold standard treatment. There is evidence, however, that there is an
      inflammatory component associated with trigger points and that obtaining a local twitch
      response is associated with a decrease in local inflammation at the site of a trigger point.
      The combination of injecting an anti-inflammatory medication and obtaining a local twitch
      response has never been studied. The purpose of this study is to examine the comparative
      effectiveness of injectable substances on patient outcome after a TPI with LTR identified,
      namely a CS (dexamethasone), a NSAID (ketorolac), or only a local anesthetic (lidocaine).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of Participants With a Responder Rate Greater Than 50% on the Numeric Rating Pain Scale (NRS) Improvement
time frame: Pre-Post Injections Up to Three Months
description: Participants in this study underwent TPIs by the following method. The needle was inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. This was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain, one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).
measure: Numeric Rating Pain Scale (NRS) at Baseline and Three Months.
time frame: Pre-Injection and Three Month Post Injection(s)
description: TPI were treated with a needle inserted into the trigger point with the goal of eliciting a local twitch responses(LTRs). When a LTR was obtained, 0.1mL of randomized drug was injected into that location within the muscle. This was repeated until LTRs disappeared, or 1.0mL had been injected, whichever came first. Such was performed in a similar manner for all affected muscles, up to a maximum of 2mL. Participants self-report their brief pain inventory at each of their injections (up to four subsequent injections) based off of the standardized Numeric Rating pain Scale (NRS). The NRS is nationally recognized numeric scale from zero to ten, with zero being an example of no pain,one to three would demonstrate mild pain, four to six would be moderate pain, seven to nine would be severe pain and a ten would be the worst pain possible. Improvement in BPI was determined if their NRS score went down with each injection(s).
measure: Brief Pain Inventory (BPI) - Modified
time frame: Baseline and Three Months
description: The BPI was evaluated on a scale from 0-10. Zero would mean no interference and 10 would be calculated at complete interferences. We used a 7-point questionnaire about pain. All scores were calculated at baseline and three months.
arm group label: Ketorolac
arm group type: Experimental
description: Participants may be randomized to receive Ketorolac for their TPI.
arm group label: Lidocaine
arm group type: Experimental
description: Participants may be randomized to receive Lidocaine for their TPI.
arm group label: Dexamethasone
arm group type: Experimental
description: Participants may be randomized to receive Dexamethasone for their TPI.
intervention type: Drug
intervention name: Ketorolac
description: Participants may be randomized to receive Ketorolac for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.
arm group label: Ketorolac
other name: Toradol
intervention type: Drug
intervention name: Lidocaine
description: Participants may be randomized to receive Lidocaine for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.
arm group label: Lidocaine
other name: Xylocaine
intervention type: Drug
intervention name: Dexamethasone
description: Participants may be randomized to receive Dexamethasone for their TPI. This randomized study will compare the efficacy of the three substances used in TPIs.
arm group label: Dexamethasone
other name: Decadron
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Dan Cushman, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
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responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: Daniel Cushman
investigator title: Assistant Professor
mesh term: Dexamethasone
mesh term: Ketorolac
mesh term: Lidocaine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination of this study due to low subject enrollment, lack of participant follow-up to substantiated end of study measures. There was not enough reported data to provide statistically pertinent or relevant analysis.
point of contact: 