<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/NCT03035942</url>
  </required_header>
  <id_info>
    <org_study_id>PUCSP 1863886</org_study_id>
    <nct_id>NCT03035942</nct_id>
  </id_info>
  <brief_title>Quality of Recovery After Dexamethasone, Ondansetron or Placebo Intrathecal Morphine Administration</brief_title>
  <official_title>Role of Dexamethasone or Ondansetron in the Quality of Recovery After Intrathecal Morphine Administration in Patients Undergoing Lower Limb Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pontificia Universidade Catolica de Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pontificia Universidade Catolica de Sao Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate not only the occurrence of side effects, but the quality&#xD;
      of the recovery (QoR-40 Questionnaire) of patients submitted to spinal anesthesia with&#xD;
      administration of low doses (0.1 mg) of intrathecal morphine for the surgical treatment of&#xD;
      fractures in one of the lower limbs and who will receive prophylactic ondansetron (4mg),&#xD;
      dexamethasone (8mg) or placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomised, double-blinded trial was approved by the Research Ethics Committee of the&#xD;
      School of Medical and Health Sciences, Pontifical Catholic University of São Paulo (Sorocaba,&#xD;
      São Paulo - Brazil), on June 14 2016, CAAE (Presentation Certificate for Ethical&#xD;
      Appreciation) 58208015.7.0000.5373 (Chairperson Prof. J.A. Costa). On the day of surgery,&#xD;
      after completion of the pre-anesthetic evaluation and due explanations of the study, consent&#xD;
      will be obtained. No participant will take any pre-anesthetic medication before surgery.&#xD;
      Subjects will be randomised using a computer-generated (www.random.org) table of random&#xD;
      numbers into 3 groups: S (saline), D (dexamethasone 8 mg), or O (ondansetron 4 mg). Group&#xD;
      assignments will be sealed in sequentially numbered opaque envelopes that were opened after&#xD;
      patient inclusion in the study. All care providers, researchers, and patients will be blinded&#xD;
      to group assignments. Study 5-mL syringes will be prepared by a nurse independent of the&#xD;
      study. Normal saline (5 mL total volume), dexamethasone (made up to 5 mL with normal saline),&#xD;
      or ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe&#xD;
      which will be offered to the anesthesia provider after the opaque envelope was opened.&#xD;
&#xD;
      After arrival in the operating room, standard ASA (American Society of Anesthesiologists)&#xD;
      monitors will be applied. Immediately after venoclysis,e.v. midazolam will be administered as&#xD;
      titrated doses to achieve 3 or 4 on Ramsay scale. Spinal puncture will be performed with the&#xD;
      patient in the seated position in the median or paramedian line at L3-L4 or L2-L3 interspace&#xD;
      using a 26-gauge Quincke needle. Anesthesia will be established with a single bolus of 0.5%&#xD;
      hyperbaric bupivacaine (17.5 mg if ≥ 70 kg or expected surgery duration &gt; 150 minutes and 15&#xD;
      mg if &lt; 70 kg) and preservative-free morphine 0.1 mg. Normal saline will be used for fluid&#xD;
      replacement therapy. In case of failure of spinal anesthesia, the technique will be repeated&#xD;
      or a general approach will be performed and the patient will be excluded from the study.&#xD;
      Titrated doses of midazolam (up to 10 mg) or propofol continuous infusion will be&#xD;
      administered to achieve perioperative sedation (≥4 on Ramsay scale). Supplemental oxygen 5&#xD;
      L/min via a vent mask will be administered during and after surgery.&#xD;
&#xD;
      Postanesthesia care unit (PACU) All patients will be transferred to the PACU. Data related to&#xD;
      the occurrence of pain, nausea, vomiting, pruritus, urinary retention and time to Aldrete&#xD;
      score ≥ 9 at the PACU will be recorded. Pain will be assessed every 15 minutes using a 0-10&#xD;
      numeric pain rating scale (NRS), where zero meant no pain and 10 the worst imaginable pain.&#xD;
      Morphine (1 to 2 mg) was administered intravenously every 10 minutes to maintain the pain&#xD;
      score below 4 (1 mg when the pain score was &lt;7 and 2 mg when it was ≥7). Postoperative nausea&#xD;
      and vomiting (PONV) will be treated with dimenhydrinate (30 mg) intravenously. Pruritus will&#xD;
      be classified as follow: 0 - no symptoms, 1 - 3 - mild symptoms, 3 - 7 moderate symptoms and&#xD;
      7 - 10 - severe symptoms. Nalbuphine 5 mg intravenously will be administered when score &gt; 4.&#xD;
&#xD;
      Ward Following discharge from the PACU (minimum stay 60 minutes and Aldrete score ≥ 9), all&#xD;
      of the participants were given ketoprofen (100 mg) every 12 hours and dipyrone (30 mg.kg-1,&#xD;
      maximum 1 g) every six hours intravenously. Whenever patients judged that their analgesia was&#xD;
      insufficient, tramadol (100 mg) was administered intravenously at eight-hour minimum&#xD;
      intervals as needed. Postoperative nausea and vomiting (PONV) were treated with&#xD;
      dimenhydrinate (30 mg) intravenously. An investigator who was blinded to group assignment&#xD;
      collected all postoperative outcome data 24 hours after surgical procedure. Subjects were&#xD;
      asked to rate the higher score of pain (NRS) during the hospital ward stay. Tramadol&#xD;
      consumption, occurrence of urinary retention and the number of nausea and vomiting episodes&#xD;
      were also recorded. These findings were confirmed with the ward nursing staff. All subjects&#xD;
      stayed at hospital for at least 24 hours.&#xD;
&#xD;
      Data Collection The baseline QoR-40 questionnaire was completed by the subjects after&#xD;
      informed consent was obtained in the preoperative holding area and 24 hours after surgery by&#xD;
      a blinded investigator. The QoR-40 questionnaire evaluates five dimensions of recovery&#xD;
      (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items;&#xD;
      physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point&#xD;
      Likert scale: none of the time, some of the time, usually, most of the time, and all the&#xD;
      time. The total score on the QoR-40 ranges from 40 (very poor quality of recovery) to 200&#xD;
      (best quality of recovery).&#xD;
&#xD;
      The primary outcome of interest will be the QoR-40 score on postoperative day 1 (POD1).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2, 2017</start_date>
  <completion_date type="Actual">November 4, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2018</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>
    <intervention_model_description>Prospective, randomized, controlled, double-blinded</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Group assignments will be sealed in sequentially numbered opaque envelopes that were opened after patient inclusion in the study. All care providers, researchers, and patients will be blinded to group assignments. Study 5-mL syringes will be prepared by a nurse independent of the study. Normal saline (5 mL total volume), dexamethasone (made up to 5 mL with normal saline), or ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Quality of Recovery</measure>
    <time_frame>Twenty four hours after surgery by a blinded investigator</time_frame>
    <description>Quality of Recovery Questionnaire (QoR-40). Minimum score 40 (very poor quality of recovery) and maximun score 200 (excellent quality of recovery). Higher scores mean better outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nausea and Vomiting During PACU Staying</measure>
    <time_frame>4h</time_frame>
    <description>The occurrence of PONV will be registered during the PACU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Pruritus</measure>
    <time_frame>24 hours</time_frame>
    <description>The occurrence of localized or generalized itching (patients who answered yes or no)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain During Postanesthesia Care Unit and Ward Stay (Numeric Rating Scale - NRS)</measure>
    <time_frame>24 hours</time_frame>
    <description>Pain were assessed every 15 minutes during postanesthesia care unit, where zero meant no pain and 10 the worst imaginable pain (higher values represent worse outcome). Twenty four hours after surgery, patients were asked to describe the highest pain score (NRS) during ward stay.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Fractures, Bone</condition>
  <condition>Nausea and Vomiting, Postoperative</condition>
  <condition>Pruritus</condition>
  <condition>Morphine Adverse Reaction</condition>
  <condition>Satisfaction, Personal</condition>
  <arm_group>
    <arm_group_label>D Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dexamethasone 8 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>O group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ondansetron 4 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>S group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline (5 mL total volume)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
    <arm_group_label>D Group</arm_group_label>
    <other_name>D Group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron</intervention_name>
    <description>Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
    <arm_group_label>O group</arm_group_label>
    <other_name>O Group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
    <arm_group_label>S group</arm_group_label>
    <other_name>Placebo Group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ASA physical status I or II, who will scheduled to undergo surgical treatment of lower&#xD;
             limb fractures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who:&#xD;
&#xD;
        (i) refused to participate in the study;&#xD;
&#xD;
        (ii) were not able to communicate due to alterations in the level of consciousness, or&#xD;
        neurologic, or psychiatric disease;&#xD;
&#xD;
        (iii) presented with contraindication to any of the drugs used in the present study;&#xD;
&#xD;
        (iv) had history of alcohol or drug abuse and&#xD;
&#xD;
        (v) had surgery in the last 10 days were excluded.&#xD;
&#xD;
        Reasons for exclusion after randomisation will be protocol violations or if the anesthesia&#xD;
        technique was changed from a spinal to a general approach.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eduardo T Moro, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>PUC São Paulo University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Santa Lucinda Hospital</name>
      <address>
        <city>Sorocaba</city>
        <state>SP</state>
        <zip>18030-230</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Jacobson L, Chabal C, Brody MC, Ward RJ, Wasse L. Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. Pain. 1990 Nov;43(2):141-148. doi: 10.1016/0304-3959(90)91066-R.</citation>
    <PMID>2087326</PMID>
  </reference>
  <reference>
    <citation>Slappendel R, Weber EW, Dirksen R, Gielen MJ, van Limbeek J. Optimization of the dose of intrathecal morphine in total hip surgery: a dose-finding study. Anesth Analg. 1999 Apr;88(4):822-6. doi: 10.1097/00000539-199904000-00026.</citation>
    <PMID>10195531</PMID>
  </reference>
  <reference>
    <citation>Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015 Feb 17;15:18. doi: 10.1186/1471-2253-15-18.</citation>
    <PMID>25971957</PMID>
  </reference>
  <reference>
    <citation>Braga AA, Frias JA, Braga FS, Poterio GB, Hirata ES, Torres NA. Spinal anesthesia for cesarean section. Use of hyperbaric bupivacaine (10mg) combined with different adjuvants. Rev Bras Anestesiol. 2012 Nov-Dec;62(6):775-87. doi: 10.1016/S0034-7094(12)70178-2.</citation>
    <PMID>23176986</PMID>
  </reference>
  <reference>
    <citation>Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage. 2001 Feb;21(2):151-68. doi: 10.1016/s0885-3924(00)00256-6.</citation>
    <PMID>11226766</PMID>
  </reference>
  <reference>
    <citation>Griffiths JD, Gyte GM, Paranjothy S, Brown HC, Broughton HK, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD007579. doi: 10.1002/14651858.CD007579.pub2.</citation>
    <PMID>22972112</PMID>
  </reference>
  <reference>
    <citation>Wu JI, Lo Y, Chia YY, Liu K, Fong WP, Yang LC, Tan PH. Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination. Int J Obstet Anesth. 2007 Apr;16(2):122-7. doi: 10.1016/j.ijoa.2006.11.004. Epub 2007 Feb 1.</citation>
    <PMID>17275282</PMID>
  </reference>
  <reference>
    <citation>Szarvas S, Chellapuri RS, Harmon DC, Owens J, Murphy D, Shorten GD. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery. Anesth Analg. 2003 Jul;97(1):259-63, table of contents. doi: 10.1213/01.ane.0000066310.49139.2a.</citation>
    <PMID>12818978</PMID>
  </reference>
  <reference>
    <citation>Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5. doi: 10.1093/oxfordjournals.bja.a013366.</citation>
    <PMID>10740540</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <results_first_submitted>December 9, 2019</results_first_submitted>
  <results_first_submitted_qc>March 5, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 19, 2020</results_first_posted>
  <last_update_submitted>March 5, 2020</last_update_submitted>
  <last_update_submitted_qc>March 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pontificia Universidade Catolica de Sao Paulo</investigator_affiliation>
    <investigator_full_name>Eduardo Toshiyuki Moro</investigator_full_name>
    <investigator_title>Assistant Professor, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Intrathecal morphine</keyword>
  <keyword>Nausea and vomiting</keyword>
  <keyword>Quality of recovery</keyword>
  <keyword>Patient satisfaction</keyword>
  <keyword>Pruritus</keyword>
  <keyword>Postoperative pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pruritus</mesh_term>
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
    <mesh_term>Postoperative Nausea and Vomiting</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Ondansetron</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>February 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03035942/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03035942/Prot_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>O Group</title>
          <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="P2">
          <title>D Group</title>
          <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="P3">
          <title>S Group</title>
          <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="45"/>
                <participants group_id="P3" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="41"/>
                <participants group_id="P3" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>O Group</title>
          <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="B2">
          <title>D Group</title>
          <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="B3">
          <title>S Group</title>
          <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</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="37"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="40"/>
            <count group_id="B4" value="118"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="37"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="118"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34" lower_limit="24" upper_limit="47"/>
                    <measurement group_id="B2" value="40" lower_limit="26" upper_limit="54"/>
                    <measurement group_id="B3" value="35" lower_limit="25" upper_limit="49"/>
                    <measurement group_id="B4" value="40" lower_limit="25" upper_limit="49"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </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>Brazil</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Physical status ASA 1 (health person)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Physical status ASA 2 (mild systemic disease)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index</title>
          <units>kg/m^2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="41"/>
                    <count group_id="B3" value="40"/>
                    <count group_id="B4" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25" lower_limit="24" upper_limit="28"/>
                    <measurement group_id="B2" value="26" lower_limit="24" upper_limit="28"/>
                    <measurement group_id="B3" value="27" lower_limit="24" upper_limit="29"/>
                    <measurement group_id="B4" value="26" lower_limit="24" upper_limit="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quality of Recovery</title>
        <description>Quality of Recovery Questionnaire (QoR-40). Minimum score 40 (very poor quality of recovery) and maximun score 200 (excellent quality of recovery). Higher scores mean better outcome</description>
        <time_frame>Twenty four hours after surgery by a blinded investigator</time_frame>
        <group_list>
          <group group_id="O1">
            <title>O Group</title>
            <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O2">
            <title>D Group</title>
            <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O3">
            <title>S Group</title>
            <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Recovery</title>
          <description>Quality of Recovery Questionnaire (QoR-40). Minimum score 40 (very poor quality of recovery) and maximun score 200 (excellent quality of recovery). Higher scores mean better outcome</description>
          <units>Score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="41"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="184" lower_limit="179" upper_limit="195"/>
                    <measurement group_id="O2" value="187" lower_limit="181" upper_limit="196"/>
                    <measurement group_id="O3" value="185" lower_limit="176" upper_limit="196"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Nausea and Vomiting During PACU Staying</title>
        <description>The occurrence of PONV will be registered during the PACU</description>
        <time_frame>4h</time_frame>
        <group_list>
          <group group_id="O1">
            <title>O Group</title>
            <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O2">
            <title>D Group</title>
            <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O3">
            <title>S Group</title>
            <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
        </group_list>
        <measure>
          <title>Nausea and Vomiting During PACU Staying</title>
          <description>The occurrence of PONV will be registered during the PACU</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="41"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Pruritus</title>
        <description>The occurrence of localized or generalized itching (patients who answered yes or no)</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>O Group</title>
            <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O2">
            <title>D Group</title>
            <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O3">
            <title>S Group</title>
            <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Pruritus</title>
          <description>The occurrence of localized or generalized itching (patients who answered yes or no)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="41"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain During Postanesthesia Care Unit and Ward Stay (Numeric Rating Scale - NRS)</title>
        <description>Pain were assessed every 15 minutes during postanesthesia care unit, where zero meant no pain and 10 the worst imaginable pain (higher values represent worse outcome). Twenty four hours after surgery, patients were asked to describe the highest pain score (NRS) during ward stay.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>D Group</title>
            <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O2">
            <title>O Group</title>
            <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
          <group group_id="O3">
            <title>S Group</title>
            <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
          </group>
        </group_list>
        <measure>
          <title>Pain During Postanesthesia Care Unit and Ward Stay (Numeric Rating Scale - NRS)</title>
          <description>Pain were assessed every 15 minutes during postanesthesia care unit, where zero meant no pain and 10 the worst imaginable pain (higher values represent worse outcome). Twenty four hours after surgery, patients were asked to describe the highest pain score (NRS) during ward stay.</description>
          <units>Score on a scale (NRS)</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="41"/>
                <count group_id="O3" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="5"/>
                    <measurement group_id="O2" value="5" lower_limit="3" upper_limit="7"/>
                    <measurement group_id="O3" value="2" lower_limit="0" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>One week</time_frame>
      <desc>The occurrence of fail of spinal anesthesia, allergic reactions, urinary retention, respiratory depression were recorded.</desc>
      <group_list>
        <group group_id="E1">
          <title>D Group</title>
          <description>Dexamethasone 8 mg&#xD;
Dexamethasone: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="E2">
          <title>O Group</title>
          <description>Ondansetron 4 mg&#xD;
Ondansetron: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</description>
        </group>
        <group group_id="E3">
          <title>S Group</title>
          <description>Normal saline (5 mL total volume)&#xD;
Saline: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.</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="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="45"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Fail of spinal anesthesia</sub_title>
                <description>A second attempt was necessary or the technique was changed to general anesthesia</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="45"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="45"/>
              </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>Dr. Eduardo Toshiyuki Moro</name_or_title>
      <organization>Pontificia Catholic University of Sao Paulo</organization>
      <phone>+5515997728015</phone>
      <email>edumoro85@gmail.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/NCT03035942
org study id: PUCSP 1863886
nct id: NCT03035942
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to evaluate not only the occurrence of side effects, but the quality
      of the recovery (QoR-40 Questionnaire) of patients submitted to spinal anesthesia with
      administration of low doses (0.1 mg) of intrathecal morphine for the surgical treatment of
      fractures in one of the lower limbs and who will receive prophylactic ondansetron (4mg),
      dexamethasone (8mg) or placebo.
This randomised, double-blinded trial was approved by the Research Ethics Committee of the
      School of Medical and Health Sciences, Pontifical Catholic University of São Paulo (Sorocaba,
      São Paulo - Brazil), on June 14 2016, CAAE (Presentation Certificate for Ethical
      Appreciation) 58208015.7.0000.5373 (Chairperson Prof. J.A. Costa). On the day of surgery,
      after completion of the pre-anesthetic evaluation and due explanations of the study, consent
      will be obtained. No participant will take any pre-anesthetic medication before surgery.
      Subjects will be randomised using a computer-generated (www.random.org) table of random
      numbers into 3 groups: S (saline), D (dexamethasone 8 mg), or O (ondansetron 4 mg). Group
      assignments will be sealed in sequentially numbered opaque envelopes that were opened after
      patient inclusion in the study. All care providers, researchers, and patients will be blinded
      to group assignments. Study 5-mL syringes will be prepared by a nurse independent of the
      study. Normal saline (5 mL total volume), dexamethasone (made up to 5 mL with normal saline),
      or ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe
      which will be offered to the anesthesia provider after the opaque envelope was opened.

      After arrival in the operating room, standard ASA (American Society of Anesthesiologists)
      monitors will be applied. Immediately after venoclysis,e.v. midazolam will be administered as
      titrated doses to achieve 3 or 4 on Ramsay scale. Spinal puncture will be performed with the
      patient in the seated position in the median or paramedian line at L3-L4 or L2-L3 interspace
      using a 26-gauge Quincke needle. Anesthesia will be established with a single bolus of 0.5%
      hyperbaric bupivacaine (17.5 mg if ≥ 70 kg or expected surgery duration > 150 minutes and 15
      mg if < 70 kg) and preservative-free morphine 0.1 mg. Normal saline will be used for fluid
      replacement therapy. In case of failure of spinal anesthesia, the technique will be repeated
      or a general approach will be performed and the patient will be excluded from the study.
      Titrated doses of midazolam (up to 10 mg) or propofol continuous infusion will be
      administered to achieve perioperative sedation (≥4 on Ramsay scale). Supplemental oxygen 5
      L/min via a vent mask will be administered during and after surgery.

      Postanesthesia care unit (PACU) All patients will be transferred to the PACU. Data related to
      the occurrence of pain, nausea, vomiting, pruritus, urinary retention and time to Aldrete
      score ≥ 9 at the PACU will be recorded. Pain will be assessed every 15 minutes using a 0-10
      numeric pain rating scale (NRS), where zero meant no pain and 10 the worst imaginable pain.
      Morphine (1 to 2 mg) was administered intravenously every 10 minutes to maintain the pain
      score below 4 (1 mg when the pain score was <7 and 2 mg when it was ≥7). Postoperative nausea
      and vomiting (PONV) will be treated with dimenhydrinate (30 mg) intravenously. Pruritus will
      be classified as follow: 0 - no symptoms, 1 - 3 - mild symptoms, 3 - 7 moderate symptoms and
      7 - 10 - severe symptoms. Nalbuphine 5 mg intravenously will be administered when score > 4.

      Ward Following discharge from the PACU (minimum stay 60 minutes and Aldrete score ≥ 9), all
      of the participants were given ketoprofen (100 mg) every 12 hours and dipyrone (30 mg.kg-1,
      maximum 1 g) every six hours intravenously. Whenever patients judged that their analgesia was
      insufficient, tramadol (100 mg) was administered intravenously at eight-hour minimum
      intervals as needed. Postoperative nausea and vomiting (PONV) were treated with
      dimenhydrinate (30 mg) intravenously. An investigator who was blinded to group assignment
      collected all postoperative outcome data 24 hours after surgical procedure. Subjects were
      asked to rate the higher score of pain (NRS) during the hospital ward stay. Tramadol
      consumption, occurrence of urinary retention and the number of nausea and vomiting episodes
      were also recorded. These findings were confirmed with the ward nursing staff. All subjects
      stayed at hospital for at least 24 hours.

      Data Collection The baseline QoR-40 questionnaire was completed by the subjects after
      informed consent was obtained in the preoperative holding area and 24 hours after surgery by
      a blinded investigator. The QoR-40 questionnaire evaluates five dimensions of recovery
      (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items;
      physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point
      Likert scale: none of the time, some of the time, usually, most of the time, and all the
      time. The total score on the QoR-40 ranges from 40 (very poor quality of recovery) to 200
      (best quality of recovery).

      The primary outcome of interest will be the QoR-40 score on postoperative day 1 (POD1).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, randomized, controlled, double-blinded
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Group assignments will be sealed in sequentially numbered opaque envelopes that were opened after patient inclusion in the study. All care providers, researchers, and patients will be blinded to group assignments. Study 5-mL syringes will be prepared by a nurse independent of the study. Normal saline (5 mL total volume), dexamethasone (made up to 5 mL with normal saline), or ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened.
measure: Quality of Recovery
time frame: Twenty four hours after surgery by a blinded investigator
description: Quality of Recovery Questionnaire (QoR-40). Minimum score 40 (very poor quality of recovery) and maximun score 200 (excellent quality of recovery). Higher scores mean better outcome
measure: Nausea and Vomiting During PACU Staying
time frame: 4h
description: The occurrence of PONV will be registered during the PACU
measure: Number of Participants With Pruritus
time frame: 24 hours
description: The occurrence of localized or generalized itching (patients who answered yes or no)
measure: Pain During Postanesthesia Care Unit and Ward Stay (Numeric Rating Scale - NRS)
time frame: 24 hours
description: Pain were assessed every 15 minutes during postanesthesia care unit, where zero meant no pain and 10 the worst imaginable pain (higher values represent worse outcome). Twenty four hours after surgery, patients were asked to describe the highest pain score (NRS) during ward stay.
arm group label: D Group
arm group type: Experimental
description: Dexamethasone 8 mg
arm group label: O group
arm group type: Experimental
description: Ondansetron 4 mg
arm group label: S group
arm group type: Placebo Comparator
description: Normal saline (5 mL total volume)
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.
arm group label: D Group
other name: D Group
intervention type: Drug
intervention name: Ondansetron
description: Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.
arm group label: O group
other name: O Group
intervention type: Drug
intervention name: Saline
description: Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.
arm group label: S group
other name: Placebo Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Eduardo T Moro, Professor
role: Principal Investigator
affiliation: PUC São Paulo University
facility: 
country: Brazil
citation: Jacobson L, Chabal C, Brody MC, Ward RJ, Wasse L. Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. Pain. 1990 Nov;43(2):141-148. doi: 10.1016/0304-3959(90)91066-R.
PMID: 2087326
citation: Slappendel R, Weber EW, Dirksen R, Gielen MJ, van Limbeek J. Optimization of the dose of intrathecal morphine in total hip surgery: a dose-finding study. Anesth Analg. 1999 Apr;88(4):822-6. doi: 10.1097/00000539-199904000-00026.
PMID: 10195531
citation: Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015 Feb 17;15:18. doi: 10.1186/1471-2253-15-18.
PMID: 25971957
citation: Braga AA, Frias JA, Braga FS, Poterio GB, Hirata ES, Torres NA. Spinal anesthesia for cesarean section. Use of hyperbaric bupivacaine (10mg) combined with different adjuvants. Rev Bras Anestesiol. 2012 Nov-Dec;62(6):775-87. doi: 10.1016/S0034-7094(12)70178-2.
PMID: 23176986
citation: Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage. 2001 Feb;21(2):151-68. doi: 10.1016/s0885-3924(00)00256-6.
PMID: 11226766
citation: Griffiths JD, Gyte GM, Paranjothy S, Brown HC, Broughton HK, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD007579. doi: 10.1002/14651858.CD007579.pub2.
PMID: 22972112
citation: Wu JI, Lo Y, Chia YY, Liu K, Fong WP, Yang LC, Tan PH. Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination. Int J Obstet Anesth. 2007 Apr;16(2):122-7. doi: 10.1016/j.ijoa.2006.11.004. Epub 2007 Feb 1.
PMID: 17275282
citation: Szarvas S, Chellapuri RS, Harmon DC, Owens J, Murphy D, Shorten GD. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery. Anesth Analg. 2003 Jul;97(1):259-63, table of contents. doi: 10.1213/01.ane.0000066310.49139.2a.
PMID: 12818978
citation: Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5. doi: 10.1093/oxfordjournals.bja.a013366.
PMID: 10740540
responsible party type: Principal Investigator
investigator affiliation: Pontificia Universidade Catolica de Sao Paulo
investigator full name: Eduardo Toshiyuki Moro
investigator title: Assistant Professor, MD, PhD
mesh term: Pruritus
mesh term: Nausea
mesh term: Vomiting
mesh term: Postoperative Nausea and Vomiting
mesh term: Fractures, Bone
mesh term: Dexamethasone
mesh term: Ondansetron
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 