<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/NCT02973958</url>
  </required_header>
  <id_info>
    <org_study_id>REB16-1876</org_study_id>
    <nct_id>NCT02973958</nct_id>
  </id_info>
  <brief_title>Evaluating Pain Outcomes of Ketorolac Administration in Children Undergoing Circumcision</brief_title>
  <official_title>A Pilot Study Evaluating Pain Outcomes of Ketorolac Administration in Children Undergoing Circumcision</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alberta Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alberta Children's Hospital</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Circumcision is the most common surgical procedure performed by Pediatric Urologists.&#xD;
      Ketorolac has been shown to have an efficacy similar to morphine in multi-modal analgesic&#xD;
      regimens without the commonly associated adverse effects. This study aims to see if giving&#xD;
      ketorolac during the operation will result in better pain control. We hypothesize that&#xD;
      ketorolac will result in pain control similar to morphine with a lower incidence of side&#xD;
      effects such as nausea and vomiting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective, randomized, single-blinded study will be conducted from January 2017- December&#xD;
      2017. A total of two groups will present. Patients with planned circumcision surgery will&#xD;
      initially be identified by the surgeon. Patients will then be randomized into treatment&#xD;
      (perioperative ketorolac) or control groups (no ketorolac).&#xD;
&#xD;
      A computer-generated randomized block design program will be used to allocate patients to&#xD;
      either the treatment (ketorolac) or control (no ketorolac) group. All children will receive a&#xD;
      15 mg/kg oral dose of acetaminophen prior to surgery unless contraindicated. General&#xD;
      anesthesia will be induced with sevoflurane via facemask. After establishing venous access, a&#xD;
      laryngeal mask will be inserted, and anesthesia maintained with 1 minimum alveolar anesthetic&#xD;
      concentration (MAC) of sevoflurane in oxygen/air 50/50 mixture. The DPNB nerve block will be&#xD;
      performed by a pediatric urologist using a 23 GA needle inserted below the Buck fascia. Once&#xD;
      the needle tip is positioned appropriately, and after a negative aspiration test, 0.2mL/kg&#xD;
      (maximum 10mL) of 0.25% bupivacaine is injected in small aliquots, with intermittent&#xD;
      aspiration throughout. In all patients, skin incision is performed at least 5 min after&#xD;
      placement of the nerve block. At the beginning of the circumcision procedure once the patient&#xD;
      is asleep, patients in the treatment group will receive a 0.5 mg/kg intravenous dose of&#xD;
      ketorolac. Patients will be advised to take ibuprofen and acetaminophen post-operatively as&#xD;
      needed.&#xD;
&#xD;
      Patients' demographic information, time needed to perform the block, time of block onset and&#xD;
      duration of surgery will be recorded. The mean arterial pressure, heart rate and oxygen&#xD;
      saturation, expired sevoflurane end tidal concentration and MAC will be systematically&#xD;
      collected pre-operatively, intra-operatively and post-operatively in the recovery room. The&#xD;
      primary outcome of post-operative pain will be evaluated through the use of the Face, Legs,&#xD;
      Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a&#xD;
      nurse or research assistant blinded to the anesthetic technique. The usage of these two&#xD;
      scales will be performed as deemed appropriate by the research assistant. The FLACC scale&#xD;
      will be used in children who have difficulty verbalizing pain and in sleeping children&#xD;
      (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of&#xD;
      self-assessment. The FLACC score is a well-established postoperative pain measure using 5&#xD;
      items scored between 0-2, which has been validated in patients from 6 months up to 7 years of&#xD;
      age (9.10). The Wong-Baker FACES pain scale that has been used post-operatively that allows&#xD;
      patients to select a face that relates to their current feeling of pain (11). These faces are&#xD;
      rated on a scale of 10. A FLACC or Wong-Baker FACES score will be recorded every 15 minutes&#xD;
      for the first hour and every 30 minutes for up to 2 hours following discharge from the PACU&#xD;
      into the day stay surgical unit. If the score is found to be &gt;3 (moderate pain 4-6, severe&#xD;
      pain 7-10), the patient will receive an intravenous morphine dose of 0.05mg/kg. An additional&#xD;
      dose may be given 15 minutes following the initial dose of morphine if analgesia is&#xD;
      inadequate (score &gt;4). Postoperatively, the child will be monitored every 15 minutes during&#xD;
      the first hour and every 30 minutes for the next 2 hours until discharge home. Discharge will&#xD;
      be based on normal institutional criteria including level of awareness, hemodynamic stability&#xD;
      and absence of pain, bleeding, nausea and vomiting. Prior to discharge, parents will be&#xD;
      provided with any additional analgesics required at home and will be contacted 24 hours&#xD;
      following their surgery to complete the parents' postoperative pain measure (PPPM) (12). The&#xD;
      PPPM is a well-established post-operative pain assessment tool with high inter-rater&#xD;
      reliability and construct validity, which has been designed specifically for use by parents&#xD;
      in the post-operative care of their children. The measure includes 15 items scored between 0&#xD;
      and 1. The questionnaire will be completed over the telephone at a time corresponding to 24&#xD;
      hours post-surgical closure. Amount of pain and analgesia consumption data will then be&#xD;
      collected by contacting the parents 24 hours post procedure.&#xD;
&#xD;
      As there are no previous studies analyzing the post-operative analgesic effects of ketorolac&#xD;
      in pediatric patients undergoing circumcision this study will act as a pilot study. A total&#xD;
      sample size of 30 patients will be used based on previous recommendations for pilot studies&#xD;
      and accounting for 20% attrition. There will be 15 patients in both the ketorolac and no&#xD;
      ketorolac groups.&#xD;
&#xD;
      The primary outcome variable will be the averaged FLACC or Wong-Baker FACES pain score during&#xD;
      hospital stay (average of all pain scores taken every 15 minutes for the first hour and every&#xD;
      30 minutes thereafter until discharge). Normality (using the Shapiro-Wilk test) will be&#xD;
      assessed for the primary outcome variable, as this will guide our choice of parametric or&#xD;
      non-parametric statistical analysis (e.g. unpaired t-test or Mann-Whitney U test). We will&#xD;
      also complete statistical analysis to assess differences in patient characteristics (e.g.&#xD;
      weight, height, age) and pre-op pain scores between the two groups. As such, Shapiro-Wilk&#xD;
      tests will be required to assess normality and guide test selection. With respect to within&#xD;
      factor comparisons, repeated measures ANOVA analysis with post-hoc Bonferroni correction for&#xD;
      multiple comparisons will be used to assess differences in pain scores within patients&#xD;
      receiving the same treatment (e.g. to access whether significant differences in pain scores&#xD;
      occurred in patients receiving ketorolac across the time points of pain score recording). An&#xD;
      analogous within factor repeated measures ANOVA will thus be used to assess differences in&#xD;
      pain scores at collected time points in patients that did not receive ketorolac. Significant&#xD;
      differences in nominal data between the two groups will be assessed using Fisher's exact test&#xD;
      or Pearson's chi-square test for association.&#xD;
&#xD;
      An independent group of experts not directly involved in the conduct of this study will be&#xD;
      assembled by open invitation to participate. This board will periodically review and evaluate&#xD;
      the accumulated study data for participant safety, study conduct and progress, and, when&#xD;
      appropriate, efficacy. Furthermore, they will make recommendations concerning the&#xD;
      continuation, modification, or termination of the trial. The board will meet before the start&#xD;
      of the trial to discuss the protocol, definition of a quorum, and guidelines for monitoring&#xD;
      the study. Thereafter, the board will convene as often as necessary, but at least once&#xD;
      annually.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">June 28, 2018</completion_date>
  <primary_completion_date type="Actual">June 28, 2018</primary_completion_date>
  <phase>Phase 1</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>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>Immediately following the procedure</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>15 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>30 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>45 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>60 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>90 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>120 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>150 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>180 minutes post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>24 hours post-operatively</time_frame>
    <description>Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique through telephone follow-up with parental input. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total ibuprofen consumption</measure>
    <time_frame>24 hours post-operatively</time_frame>
    <description>Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total acetaminophen consumption</measure>
    <time_frame>24 hours post-operatively</time_frame>
    <description>Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of bleeding requiring medical attention</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Bleeding events will be compiled through post-anesthetic care unit, surgical short stay unit, clinic and emergency department notes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Pain, Postoperative</condition>
  <condition>Phimosis</condition>
  <condition>Paraphimosis</condition>
  <condition>Balanitis</condition>
  <arm_group>
    <arm_group_label>No ketorolac</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 mg/kg oral dose of acetaminophen is administered prior to surgery. General anesthesia will be induced with sevoflurane via facemask. After establishing venous access, a laryngeal mask will be inserted, and anesthesia maintained with 1 minimum alveolar anesthetic concentration (MAC) of sevoflurane in oxygen/air 50/50 mixture. The DPNB nerve block is done using a 23 GA needle inserted below the Buck fascia. Once the needle tip is positioned appropriately and after a negative aspiration test, 0.2mL/kg (maximum 10mL) of 0.25% bupivacaine is injected in small aliquots, with intermittent aspiration throughout. In all patients, skin incision is performed at least 5 min after placement of the nerve block. Patients will be advised to take ibuprofen and acetaminophen post-operatively as needed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exactly same as the no ketorolac group except at the beginning of the circumcision, once the patient is asleep, patients in the perioperative ketorolac group will also receive a 0.5 mg/kg intravenous dose of ketorolac.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bupivacaine</intervention_name>
    <description>See active comparator description</description>
    <arm_group_label>No ketorolac</arm_group_label>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <other_name>Marcaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevoflurane</intervention_name>
    <description>See active comparator description</description>
    <arm_group_label>No ketorolac</arm_group_label>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <other_name>Sevorane</other_name>
    <other_name>Ultane</other_name>
    <other_name>Sojourn</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>See active comparator description</description>
    <arm_group_label>No ketorolac</arm_group_label>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <other_name>Tylenol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen</intervention_name>
    <description>See active comparator description</description>
    <arm_group_label>No ketorolac</arm_group_label>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <other_name>Advil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketorolac</intervention_name>
    <description>See experimental arm description</description>
    <arm_group_label>Peri-operative ketorolac</arm_group_label>
    <other_name>Toradol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All children admitted for circumcision at the Alberta Children's Hospital&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions to local anesthetics or ketorolac&#xD;
&#xD;
          -  Bleeding diatheses&#xD;
&#xD;
          -  Coagulopathy&#xD;
&#xD;
          -  Infection at the injection site.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bryce Weber, MD FRCSC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alberta Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alberta Children's Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3B 6A8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://pubchem.ncbi.nlm.nih.gov/compound/3826</url>
    <description>Ketorolac compound summary. Pubchem Substance Website. National Center for Biotechnology, US National Library of Medicine</description>
  </link>
  <reference>
    <citation>Allan CY, Jacqueline PA, Shubhda JH. Caudal epidural block versus other methods of postoperative pain relief for circumcision in boys. Cochrane Database Syst Rev. 2003;(2):CD003005. doi: 10.1002/14651858.CD003005.</citation>
    <PMID>12804449</PMID>
  </reference>
  <reference>
    <citation>Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004 Oct 18;2004(4):CD004217. doi: 10.1002/14651858.CD004217.pub2.</citation>
    <PMID>15495086</PMID>
  </reference>
  <reference>
    <citation>American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030. No abstract available.</citation>
    <PMID>22227789</PMID>
  </reference>
  <reference>
    <citation>Adler R, Ottaway MS, Gould S. Circumcision: we have heard from the experts; now let's hear from the parents. Pediatrics. 2001 Feb;107(2):E20. doi: 10.1542/peds.107.2.e20.</citation>
    <PMID>11158494</PMID>
  </reference>
  <reference>
    <citation>Sutters KA, Levine JD, Dibble S, Savedra M, Miaskowski C. Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain. 1995 Apr;61(1):145-153. doi: 10.1016/0304-3959(94)00166-C.</citation>
    <PMID>7644238</PMID>
  </reference>
  <reference>
    <citation>Gunter JB, Varughese AM, Harrington JF, Wittkugel EP, Patankar SS, Matar MM, Lowe EE, Myer CM 3rd, Willging JP. Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Anesth Analg. 1995 Dec;81(6):1136-41. doi: 10.1097/00000539-199512000-00004.</citation>
    <PMID>7486094</PMID>
  </reference>
  <reference>
    <citation>De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424-33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29.</citation>
    <PMID>21965355</PMID>
  </reference>
  <reference>
    <citation>von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years. Pain. 2007 Jan;127(1-2):140-50. doi: 10.1016/j.pain.2006.08.014. Epub 2006 Sep 25.</citation>
    <PMID>16996689</PMID>
  </reference>
  <reference>
    <citation>Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.</citation>
    <PMID>9220806</PMID>
  </reference>
  <reference>
    <citation>Chambers CT, Hardial J, Craig KD, Court C, Montgomery C. Faces scales for the measurement of postoperative pain intensity in children following minor surgery. Clin J Pain. 2005 May-Jun;21(3):277-85. doi: 10.1097/00002508-200505000-00011.</citation>
    <PMID>15818080</PMID>
  </reference>
  <reference>
    <citation>Chambers CT, Finley AG, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-443. doi: 10.1016/S0304-3959(03)00256-2.</citation>
    <PMID>14527704</PMID>
  </reference>
  <reference>
    <citation>Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 4.4: 287-291, 2005</citation>
  </reference>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <last_update_submitted>June 28, 2018</last_update_submitted>
  <last_update_submitted_qc>June 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Alberta Children's Hospital</investigator_affiliation>
    <investigator_full_name>Bryce Weber</investigator_full_name>
    <investigator_title>Pediatric Urologist</investigator_title>
  </responsible_party>
  <keyword>Penis</keyword>
  <keyword>Pain</keyword>
  <keyword>Ketorolac</keyword>
  <keyword>Circumcision</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phimosis</mesh_term>
    <mesh_term>Balanitis</mesh_term>
    <mesh_term>Paraphimosis</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Ibuprofen</mesh_term>
    <mesh_term>Ketorolac</mesh_term>
    <mesh_term>Bupivacaine</mesh_term>
    <mesh_term>Sevoflurane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02973958
org study id: REB16-1876
nct id: NCT02973958
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Circumcision is the most common surgical procedure performed by Pediatric Urologists.
      Ketorolac has been shown to have an efficacy similar to morphine in multi-modal analgesic
      regimens without the commonly associated adverse effects. This study aims to see if giving
      ketorolac during the operation will result in better pain control. We hypothesize that
      ketorolac will result in pain control similar to morphine with a lower incidence of side
      effects such as nausea and vomiting.
Prospective, randomized, single-blinded study will be conducted from January 2017- December
      2017. A total of two groups will present. Patients with planned circumcision surgery will
      initially be identified by the surgeon. Patients will then be randomized into treatment
      (perioperative ketorolac) or control groups (no ketorolac).

      A computer-generated randomized block design program will be used to allocate patients to
      either the treatment (ketorolac) or control (no ketorolac) group. All children will receive a
      15 mg/kg oral dose of acetaminophen prior to surgery unless contraindicated. General
      anesthesia will be induced with sevoflurane via facemask. After establishing venous access, a
      laryngeal mask will be inserted, and anesthesia maintained with 1 minimum alveolar anesthetic
      concentration (MAC) of sevoflurane in oxygen/air 50/50 mixture. The DPNB nerve block will be
      performed by a pediatric urologist using a 23 GA needle inserted below the Buck fascia. Once
      the needle tip is positioned appropriately, and after a negative aspiration test, 0.2mL/kg
      (maximum 10mL) of 0.25% bupivacaine is injected in small aliquots, with intermittent
      aspiration throughout. In all patients, skin incision is performed at least 5 min after
      placement of the nerve block. At the beginning of the circumcision procedure once the patient
      is asleep, patients in the treatment group will receive a 0.5 mg/kg intravenous dose of
      ketorolac. Patients will be advised to take ibuprofen and acetaminophen post-operatively as
      needed.

      Patients' demographic information, time needed to perform the block, time of block onset and
      duration of surgery will be recorded. The mean arterial pressure, heart rate and oxygen
      saturation, expired sevoflurane end tidal concentration and MAC will be systematically
      collected pre-operatively, intra-operatively and post-operatively in the recovery room. The
      primary outcome of post-operative pain will be evaluated through the use of the Face, Legs,
      Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a
      nurse or research assistant blinded to the anesthetic technique. The usage of these two
      scales will be performed as deemed appropriate by the research assistant. The FLACC scale
      will be used in children who have difficulty verbalizing pain and in sleeping children
      (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of
      self-assessment. The FLACC score is a well-established postoperative pain measure using 5
      items scored between 0-2, which has been validated in patients from 6 months up to 7 years of
      age (9.10). The Wong-Baker FACES pain scale that has been used post-operatively that allows
      patients to select a face that relates to their current feeling of pain (11). These faces are
      rated on a scale of 10. A FLACC or Wong-Baker FACES score will be recorded every 15 minutes
      for the first hour and every 30 minutes for up to 2 hours following discharge from the PACU
      into the day stay surgical unit. If the score is found to be >3 (moderate pain 4-6, severe
      pain 7-10), the patient will receive an intravenous morphine dose of 0.05mg/kg. An additional
      dose may be given 15 minutes following the initial dose of morphine if analgesia is
      inadequate (score >4). Postoperatively, the child will be monitored every 15 minutes during
      the first hour and every 30 minutes for the next 2 hours until discharge home. Discharge will
      be based on normal institutional criteria including level of awareness, hemodynamic stability
      and absence of pain, bleeding, nausea and vomiting. Prior to discharge, parents will be
      provided with any additional analgesics required at home and will be contacted 24 hours
      following their surgery to complete the parents' postoperative pain measure (PPPM) (12). The
      PPPM is a well-established post-operative pain assessment tool with high inter-rater
      reliability and construct validity, which has been designed specifically for use by parents
      in the post-operative care of their children. The measure includes 15 items scored between 0
      and 1. The questionnaire will be completed over the telephone at a time corresponding to 24
      hours post-surgical closure. Amount of pain and analgesia consumption data will then be
      collected by contacting the parents 24 hours post procedure.

      As there are no previous studies analyzing the post-operative analgesic effects of ketorolac
      in pediatric patients undergoing circumcision this study will act as a pilot study. A total
      sample size of 30 patients will be used based on previous recommendations for pilot studies
      and accounting for 20% attrition. There will be 15 patients in both the ketorolac and no
      ketorolac groups.

      The primary outcome variable will be the averaged FLACC or Wong-Baker FACES pain score during
      hospital stay (average of all pain scores taken every 15 minutes for the first hour and every
      30 minutes thereafter until discharge). Normality (using the Shapiro-Wilk test) will be
      assessed for the primary outcome variable, as this will guide our choice of parametric or
      non-parametric statistical analysis (e.g. unpaired t-test or Mann-Whitney U test). We will
      also complete statistical analysis to assess differences in patient characteristics (e.g.
      weight, height, age) and pre-op pain scores between the two groups. As such, Shapiro-Wilk
      tests will be required to assess normality and guide test selection. With respect to within
      factor comparisons, repeated measures ANOVA analysis with post-hoc Bonferroni correction for
      multiple comparisons will be used to assess differences in pain scores within patients
      receiving the same treatment (e.g. to access whether significant differences in pain scores
      occurred in patients receiving ketorolac across the time points of pain score recording). An
      analogous within factor repeated measures ANOVA will thus be used to assess differences in
      pain scores at collected time points in patients that did not receive ketorolac. Significant
      differences in nominal data between the two groups will be assessed using Fisher's exact test
      or Pearson's chi-square test for association.

      An independent group of experts not directly involved in the conduct of this study will be
      assembled by open invitation to participate. This board will periodically review and evaluate
      the accumulated study data for participant safety, study conduct and progress, and, when
      appropriate, efficacy. Furthermore, they will make recommendations concerning the
      continuation, modification, or termination of the trial. The board will meet before the start
      of the trial to discuss the protocol, definition of a quorum, and guidelines for monitoring
      the study. Thereafter, the board will convene as often as necessary, but at least once
      annually.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
measure: Post-operative pain
time frame: Immediately following the procedure
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 15 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 30 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 45 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 60 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 90 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 120 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 150 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 180 minutes post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Post-operative pain
time frame: 24 hours post-operatively
description: Evaluated through the use of the Face, Legs, Activity, Cry, Consolability (FLACC) pain score or Wong-Baker FACES scale ascertained by a nurse or research assistant blinded to the anesthetic technique through telephone follow-up with parental input. The FLACC scale will be used in children who have difficulty verbalizing pain and in sleeping children (regardless of age) while the Wong-Baker FACES scale will be used in patients capable of self-assessment. Both scores are out of 10 and can be averaged together to quantify post-operative pain
measure: Total ibuprofen consumption
time frame: 24 hours post-operatively
description: Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up
measure: Total acetaminophen consumption
time frame: 24 hours post-operatively
description: Evaluated and compiled through anesthesia notes, post-operative nursing care notes and parental telephone follow-up
measure: Incidence of bleeding requiring medical attention
time frame: Up to 2 weeks
description: Bleeding events will be compiled through post-anesthetic care unit, surgical short stay unit, clinic and emergency department notes
arm group label: No ketorolac
arm group type: Active Comparator
description: 15 mg/kg oral dose of acetaminophen is administered prior to surgery. General anesthesia will be induced with sevoflurane via facemask. After establishing venous access, a laryngeal mask will be inserted, and anesthesia maintained with 1 minimum alveolar anesthetic concentration (MAC) of sevoflurane in oxygen/air 50/50 mixture. The DPNB nerve block is done using a 23 GA needle inserted below the Buck fascia. Once the needle tip is positioned appropriately and after a negative aspiration test, 0.2mL/kg (maximum 10mL) of 0.25% bupivacaine is injected in small aliquots, with intermittent aspiration throughout. In all patients, skin incision is performed at least 5 min after placement of the nerve block. Patients will be advised to take ibuprofen and acetaminophen post-operatively as needed.
arm group label: Peri-operative ketorolac
arm group type: Experimental
description: Exactly same as the no ketorolac group except at the beginning of the circumcision, once the patient is asleep, patients in the perioperative ketorolac group will also receive a 0.5 mg/kg intravenous dose of ketorolac.
intervention type: Drug
intervention name: Bupivacaine
description: See active comparator description
arm group label: No ketorolac
arm group label: Peri-operative ketorolac
other name: Marcaine
intervention type: Drug
intervention name: Sevoflurane
description: See active comparator description
arm group label: No ketorolac
arm group label: Peri-operative ketorolac
other name: Sevorane
other name: Ultane
other name: Sojourn
intervention type: Drug
intervention name: Acetaminophen
description: See active comparator description
arm group label: No ketorolac
arm group label: Peri-operative ketorolac
other name: Tylenol
intervention type: Drug
intervention name: Ibuprofen
description: See active comparator description
arm group label: No ketorolac
arm group label: Peri-operative ketorolac
other name: Advil
intervention type: Drug
intervention name: Ketorolac
description: See experimental arm description
arm group label: Peri-operative ketorolac
other name: Toradol
criteria: 
gender: Male
minimum age: N/A
maximum age: 18 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bryce Weber, MD FRCSC
role: Principal Investigator
affiliation: Alberta Children's Hospital
facility: 
country: Canada
url: http://pubchem.ncbi.nlm.nih.gov/compound/3826
description: Ketorolac compound summary. Pubchem Substance Website. National Center for Biotechnology, US National Library of Medicine
citation: Allan CY, Jacqueline PA, Shubhda JH. Caudal epidural block versus other methods of postoperative pain relief for circumcision in boys. Cochrane Database Syst Rev. 2003;(2):CD003005. doi: 10.1002/14651858.CD003005.
PMID: 12804449
citation: Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev. 2004 Oct 18;2004(4):CD004217. doi: 10.1002/14651858.CD004217.pub2.
PMID: 15495086
citation: American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030. No abstract available.
PMID: 22227789
citation: Adler R, Ottaway MS, Gould S. Circumcision: we have heard from the experts; now let's hear from the parents. Pediatrics. 2001 Feb;107(2):E20. doi: 10.1542/peds.107.2.e20.
PMID: 11158494
citation: Sutters KA, Levine JD, Dibble S, Savedra M, Miaskowski C. Analgesic efficacy and safety of single-dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain. 1995 Apr;61(1):145-153. doi: 10.1016/0304-3959(94)00166-C.
PMID: 7644238
citation: Gunter JB, Varughese AM, Harrington JF, Wittkugel EP, Patankar SS, Matar MM, Lowe EE, Myer CM 3rd, Willging JP. Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Anesth Analg. 1995 Dec;81(6):1136-41. doi: 10.1097/00000539-199512000-00004.
PMID: 7486094
citation: De Oliveira GS Jr, Agarwal D, Benzon HT. Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials. Anesth Analg. 2012 Feb;114(2):424-33. doi: 10.1213/ANE.0b013e3182334d68. Epub 2011 Sep 29.
PMID: 21965355
citation: von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioral) measures of pain for children and adolescents aged 3 to 18 years. Pain. 2007 Jan;127(1-2):140-50. doi: 10.1016/j.pain.2006.08.014. Epub 2006 Sep 25.
PMID: 16996689
citation: Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997 May-Jun;23(3):293-7.
PMID: 9220806
citation: Chambers CT, Hardial J, Craig KD, Court C, Montgomery C. Faces scales for the measurement of postoperative pain intensity in children following minor surgery. Clin J Pain. 2005 May-Jun;21(3):277-85. doi: 10.1097/00002508-200505000-00011.
PMID: 15818080
citation: Chambers CT, Finley AG, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-443. doi: 10.1016/S0304-3959(03)00256-2.
PMID: 14527704
citation: Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 4.4: 287-291, 2005
responsible party type: Principal Investigator
investigator affiliation: Alberta Children's Hospital
investigator full name: Bryce Weber
investigator title: Pediatric Urologist
mesh term: Phimosis
mesh term: Balanitis
mesh term: Paraphimosis
mesh term: Pain, Postoperative
mesh term: Acetaminophen
mesh term: Ibuprofen
mesh term: Ketorolac
mesh term: Bupivacaine
mesh term: Sevoflurane
sharing ipd: Undecided