<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/NCT03031795</url>
  </required_header>
  <id_info>
    <org_study_id>OH1-13-00503</org_study_id>
    <nct_id>NCT03031795</nct_id>
  </id_info>
  <brief_title>Oral Ketorolac for Pain Relief During IUD Insertion</brief_title>
  <official_title>Oral Ketorolac for Pain Relief During IUD Insertion: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OhioHealth</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>OhioHealth</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ketorolac is a non-steroidal anti-inflammatory drug (NSAID), similar to ibuprofen but it is&#xD;
      used to treat more severe pain. Ketorolac (Trade name: Toradol) is typically used after&#xD;
      surgical procedures. When taken orally, it should not cause sedation. The purpose of this&#xD;
      study is to determine if oral ketorolac is effective at reducing pain during IUD placement&#xD;
      versus a placebo tablet.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the United States, 10% of women choose an intrauterine device (IUD) for contraception.&#xD;
      With typical use, unintended pregnancy rates in the first year of IUD contraception are 0.8%&#xD;
      (Copper T) and 0.2% (LNG). It is known that long-acting, reversible contraception methods&#xD;
      reduce the long-term cost of unintended pregnancies. A common deterrent to intrauterine&#xD;
      contraception is the fear of pain during placement. Methods of pain relief during IUD&#xD;
      insertion must be fast-acting but have minimal sedation. There have been many attempts to&#xD;
      find effective pain relief during IUD placement. Neither ibuprofen nor naproxen have been&#xD;
      shown to be effective in reducing pain. Misoprostol has been used to increase cervical&#xD;
      ripening; however, pain was not decreased, and side effects of nausea and vomiting were&#xD;
      increased. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that works by&#xD;
      reversibly inhibiting cyclooxygenase-1 and 2.Time to peak plasma concentration ketorolac in&#xD;
      the oral form is 44 minutes. Studies have shown that one dose of ketorolac can be as potent&#xD;
      as morphine. Ketorolac is also well established for pain control in the immediate&#xD;
      post-operative period. A recent study showed that intramuscular ketorolac wais effective in&#xD;
      reducing pain after IUD insertion, but 20% of the participants reported that after the&#xD;
      procedure, the injection site was as painful as the IUD placement. The current study was&#xD;
      designed to evaluate if there is reduced pain during IUD placement using oral ketorolac 40-60&#xD;
      minutes before the procedure compared to a placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain Before, During and After IUD Placement</measure>
    <time_frame>Before, during and after IUD placement</time_frame>
    <description>Pain before, during and after IUD placement on a 0 (no pain) to 10 (worst possible) scale. Higher score mean a worse outcome.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Contraception</condition>
  <arm_group>
    <arm_group_label>experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ketorolac, oral, 20 mg, 1 dose, 45 minutes prior to IUD placement</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>look alike placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketorolac</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>experimental</arm_group_label>
    <other_name>Toradol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  non-pregnant&#xD;
&#xD;
          -  English speaking women&#xD;
&#xD;
          -  18 years of age or older desiring an IUD for contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  enrollment in another study&#xD;
&#xD;
          -  pre-medication with any type of analgesic medication&#xD;
&#xD;
          -  contraindication to an IUD&#xD;
&#xD;
          -  weight under 50 kg&#xD;
&#xD;
          -  allergy to non-steroidal anti-inflammatory medications&#xD;
&#xD;
          -  past medical history of liver disease, renal disease, peptic ulcer disease or recent&#xD;
             gastrointestinal bleed,&#xD;
&#xD;
          -  daily narcotic pain use&#xD;
&#xD;
          -  positive cultures for gonorrhea or chlamydia.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michelle Crawford, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OhioHealth</affiliation>
  </overall_official>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>September 13, 2017</results_first_submitted>
  <results_first_submitted_qc>August 28, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 26, 2018</results_first_posted>
  <last_update_submitted>August 28, 2018</last_update_submitted>
  <last_update_submitted_qc>August 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>intrauterine device</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketorolac</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will share our published manuscript upon request:&#xD;
Crawford M, Davy S, Book N, Elliott JO, Arora A. Oral ketorolac for pain relief during intrauterine device insertion: a double-blinded randomized controlled trial. Journal of Obstetrics and Gynaecology Canada 2017, Dec;39(12):1143-1149. doi: 10.1016/j.jogc.2017.05.014.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental</title>
          <description>ketorolac, oral, 20 mg, 1 dose, 45 minutes prior to IUD placement&#xD;
Ketorolac: Oral Tablet</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>look alike placebo&#xD;
Placebos</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ketorolac</title>
          <description>Experimental group</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Control group</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="35"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="71"/>
          </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="35"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 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_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="31.9" spread="6.7"/>
                    <measurement group_id="B2" value="30.7" spread="8.9"/>
                    <measurement group_id="B3" value="31.3" spread="7.9"/>
                  </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="35"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/ethnicity</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="35"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pain Before, During and After IUD Placement</title>
        <description>Pain before, during and after IUD placement on a 0 (no pain) to 10 (worst possible) scale. Higher score mean a worse outcome.</description>
        <time_frame>Before, during and after IUD placement</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketorolac</title>
            <description>Experimental group</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo group</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Before, During and After IUD Placement</title>
          <description>Pain before, during and after IUD placement on a 0 (no pain) to 10 (worst possible) scale. Higher score mean a worse outcome.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pain expected during the procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="2.2"/>
                    <measurement group_id="O2" value="4.5" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-procedure pain rating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="1.0"/>
                    <measurement group_id="O2" value="0.7" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tenaculum placement</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="2.2"/>
                    <measurement group_id="O2" value="3.2" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Uterine sounding</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="2.9"/>
                    <measurement group_id="O2" value="4.2" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deployment of the IUD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" spread="2.9"/>
                    <measurement group_id="O2" value="5.7" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall pain rating during the procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="2.9"/>
                    <measurement group_id="O2" value="4.9" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Level of pain 10 minutes post procedure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="1.5"/>
                    <measurement group_id="O2" value="2.5" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A 2 point difference was used to power the study. This is consistent with previous definitions of a clinically meaningful reductions in pain and provides a visually meaningful change on the 0-10 numerical rating scale with anchors at every other point, for example moving from &quot;very severe&quot; (8) to &quot;severe pain&quot; (6) or from &quot;moderate pain&quot; (4) to &quot;mild pain&quot; (2).</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.05</p_value>
            <p_value_desc>The a priori threshold for statistical significance was set at &lt; 0.05 for each row comparison with no adjustment for multiple comparisons.</p_value_desc>
            <method>Wilcoxon rank sum test</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>45 minutes prior and up to 10 minutes post IUD placement</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Experimental</title>
          <description>ketorolac, oral, 20 mg, 1 dose, 45 minutes prior to IUD placement&#xD;
Ketorolac: Oral Tablet</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>look alike placebo&#xD;
Placebos</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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>John O. Elliott PhD, MPH Research Specialist Medical Education</name_or_title>
      <organization>OhioHealth</organization>
      <phone>614-566-3643</phone>
      <email>john.elliott@ohiohealth.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03031795
org study id: OH1-13-00503
nct id: NCT03031795
lead sponsor: 
has dmc: Yes
Ketorolac is a non-steroidal anti-inflammatory drug (NSAID), similar to ibuprofen but it is
      used to treat more severe pain. Ketorolac (Trade name: Toradol) is typically used after
      surgical procedures. When taken orally, it should not cause sedation. The purpose of this
      study is to determine if oral ketorolac is effective at reducing pain during IUD placement
      versus a placebo tablet.
In the United States, 10% of women choose an intrauterine device (IUD) for contraception.
      With typical use, unintended pregnancy rates in the first year of IUD contraception are 0.8%
      (Copper T) and 0.2% (LNG). It is known that long-acting, reversible contraception methods
      reduce the long-term cost of unintended pregnancies. A common deterrent to intrauterine
      contraception is the fear of pain during placement. Methods of pain relief during IUD
      insertion must be fast-acting but have minimal sedation. There have been many attempts to
      find effective pain relief during IUD placement. Neither ibuprofen nor naproxen have been
      shown to be effective in reducing pain. Misoprostol has been used to increase cervical
      ripening; however, pain was not decreased, and side effects of nausea and vomiting were
      increased. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that works by
      reversibly inhibiting cyclooxygenase-1 and 2.Time to peak plasma concentration ketorolac in
      the oral form is 44 minutes. Studies have shown that one dose of ketorolac can be as potent
      as morphine. Ketorolac is also well established for pain control in the immediate
      post-operative period. A recent study showed that intramuscular ketorolac wais effective in
      reducing pain after IUD insertion, but 20% of the participants reported that after the
      procedure, the injection site was as painful as the IUD placement. The current study was
      designed to evaluate if there is reduced pain during IUD placement using oral ketorolac 40-60
      minutes before the procedure compared to a placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Pain Before, During and After IUD Placement
time frame: Before, during and after IUD placement
description: Pain before, during and after IUD placement on a 0 (no pain) to 10 (worst possible) scale. Higher score mean a worse outcome.
arm group label: experimental
arm group type: Experimental
description: ketorolac, oral, 20 mg, 1 dose, 45 minutes prior to IUD placement
arm group label: placebo
arm group type: Placebo Comparator
description: look alike placebo
intervention type: Drug
intervention name: Ketorolac
description: Oral Tablet
arm group label: experimental
other name: Toradol
intervention type: Drug
intervention name: Placebo
description: Oral Tablet
arm group label: placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Michelle Crawford, MD
role: Principal Investigator
affiliation: OhioHealth
responsible party type: Sponsor
mesh term: Ketorolac
sharing ipd: No
ipd description: We will share our published manuscript upon request:
Crawford M, Davy S, Book N, Elliott JO, Arora A. Oral ketorolac for pain relief during intrauterine device insertion: a double-blinded randomized controlled trial. Journal of Obstetrics and Gynaecology Canada 2017, Dec;39(12):1143-1149. doi: 10.1016/j.jogc.2017.05.014.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 