<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/NCT03250494</url>
  </required_header>
  <id_info>
    <org_study_id>17585</org_study_id>
    <nct_id>NCT03250494</nct_id>
  </id_info>
  <brief_title>Duloxetine and Dexamethasone for Improving Postoperative Pain</brief_title>
  <official_title>Impact of Duloxetine and Dexamethasone for Improving Postoperative Pain After Laparoscopic Gynecological Surgeries: a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      75 female patients were randomly allocated into one of three equal groups. Group I(GI)&#xD;
      received Dulox 60 mg orally and 100 ml 0.9% sodium chloride solution (NS) intravenous&#xD;
      infusion (IVI) over 15 min, group II(GII): received combined Dulox capsule 60 mg orally and&#xD;
      Dex 0.1mg/kg mixed with 100 ml NS IVI and group III(GIII) received identical placebo&#xD;
      duloxetine capsule and 100 ml NS IVI as a placebo for Dex, 2 hours preoperatively. Patients'&#xD;
      vitals, VAS and sedation score were assessed at 30 minutes, 1h, 2 h, 6h and 12h&#xD;
      postoperatively. Total pethidine requirements, plasma cortisol, PONV and patient's&#xD;
      satisfaction were recorded.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was designed to be a randomized, placebo-controlled, double-blinded parallel study&#xD;
      and this study was carried out at Ain-Shams university hospitals, from December 2014 to&#xD;
      January2016, on 75 female patients aged between 25 and 35 years old of the American Society&#xD;
      of Anesthesiologists (ASA) physical status I and II scheduled for elective laparoscopic&#xD;
      gynecological surgeries (for infertility) under general anesthesia. Approval was obtained&#xD;
      from the institutional ethical committee and written informed consent was obtained from all&#xD;
      patients.&#xD;
&#xD;
      Patients were not admitted to the study if any of the following criteria were present: (1)&#xD;
      patient's refusal, (2) duration of surgery more than 90 minutes, (3) allergy to any drugs of&#xD;
      the study, (4) smokers, history of drug or alcohol abuse, (5) treatment with antidepressants,&#xD;
      (6) history of diabetes or epilepsy, (7) , history of chronic pain or daily intake of&#xD;
      analgesics within 24 h before surgery, (8) treatment with systemic glucocorticoids within 4&#xD;
      weeks before surgery and (9) impaired kidney or liver functions.&#xD;
&#xD;
      Patients were randomly allocated into 3 equal groups, group (I) (GI) (n=25) each patient&#xD;
      received Dulox capsule (60mg) orally with sips of water 2 hours preoperatively and 100 ml&#xD;
      0.9% sodium chloride solution (NS) intravenous infusion (IVI) over 15 min (Placebo), group&#xD;
      (II) (GII) (n=25) each patient received combined Dulox capsule (60 mg) orally with sips of&#xD;
      water and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI over 15 min, 2 hours preoperatively and&#xD;
      group (III) (GIII) (control group) (n=25) each patient received a placebo capsule identical&#xD;
      to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone 2 hours&#xD;
      preoperatively. Dulox was presented as CYMBALTA® capsules manufactured by Lilly del Caribe&#xD;
      Inc. Imported by Elco and Dex was presented as dexamethasone sulphate ampoules 8mg in 2ml.&#xD;
      (Medical Union Pharmaceutical, Egypt MUP). Randomization was done using computer-generated&#xD;
      number table of random numbers in a 1:1 ratio and conducted using sequentially numbered,&#xD;
      opaque and sealed envelope (SNOSE). Active Dulox capsules were indistinguishable from placebo&#xD;
      capsules and placebo capsules contained starch. The study drugs were prepared by the hospital&#xD;
      pharmacy and follow-up of patients was conducted by the anesthesia residents not involved in&#xD;
      any other part of the study.&#xD;
&#xD;
      During the preoperative anesthetic evaluation, patients were familiarized with 10 cm marked&#xD;
      visual analogue scale (VAS) for PO assessment of pain, where 0 cm defines no pain and 10 cm&#xD;
      defines the maximum intolerable pain. Patients were also assured that they would receive&#xD;
      intramuscular injection (IM) of pethidine 0.5 mg / kg once they experienced pain&#xD;
      postoperatively (patients with (VAS &gt; 3).&#xD;
&#xD;
      The general anesthesia technique was standardized for all the patients as well as monitors&#xD;
      including 5 lead ECG, non- invasive blood pressure (NIBP) monitor, pulse oximetry and&#xD;
      capnography after intubation using Datascope monitors. Neuromuscular function was monitored&#xD;
      using a peripheral nerve stimulator. After establishing an intravenous (IV) line, induction&#xD;
      of general anesthesia with fentanyl (2 ug/kg) and sleeping dose of propofol followed by&#xD;
      rocuronium (0.6 mg/kg) to facilitate orotracheal intubation was done. Anesthesia was&#xD;
      maintained using isoflurane in oxygen and air. Ranitidine (50 mg/ampoule) was given diluted&#xD;
      in 10 ml 0.9% sodium chloride solution (NS) slowly (IV) over 10 minutes as a gastroprotective&#xD;
      regimen. At the end of the surgery, the residual neuromuscular paralysis was antagonized with&#xD;
      neostigmine (0.05 mg/kg) and atropine (0.01 mg/kg). After satisfactory recovery, patients&#xD;
      were extubated and transferred to the post-anesthesia care unit (PACU) where they were&#xD;
      monitored with ECG, NIBP and pulse oximetry.&#xD;
&#xD;
      Assessment of patients' vitals (HR, MAP), arterial SpO2, sedation score, visual analog scale&#xD;
      (VAS), the first analgesic requirement time and adverse effects (e.g. nausea, vomiting&#xD;
      (PONV), pruritis) were done at 30 minutes, 1h, 2 h, 6h and 12h postoperatively.&#xD;
&#xD;
      PO pain was evaluated at rest based on visual analogue scale, first time to ask for rescue&#xD;
      analgesia and total pethidine requirements in 12 hours (mg) postoperatively were recorded.&#xD;
      Assessment of sedation was according to sedation score (Ramsay sedation scale) (14).&#xD;
&#xD;
      Hypotension was considered if there was 20% decrease below the baseline for MAP and was&#xD;
      treated with IV bolus of ephedrine (3-6 mg). Bradycardia was considered if the heart rate &lt;&#xD;
      55 beats/min and was treated with IV atropine (0.01mg/kg). Respiratory depression was defined&#xD;
      as a respiratory rate less than 10 breaths/min-1 or peripheral oxygen saturation less than&#xD;
      95% and was treated with oxygen through a transparent face mask and the intermittent doses of&#xD;
      IV naloxone (0.4 mg). IV granisetron (1mg) was given in case of vomiting or after 2&#xD;
      successive episodes of nausea. Pruritus was evaluated with a 4-point scale (0=absent, 1=mild,&#xD;
      2=moderate, 3=severe or requiring treatment), and patients with severe pruritus were treated&#xD;
      with IV clemastine (TavegylR) (2 mg / ampoule).&#xD;
&#xD;
      Patient's satisfaction was done by asking the patient to answer the question, 'How would you&#xD;
      rate your experience after the surgery?' using a 7-point Likert verbal rating scale (15) and&#xD;
      acceptable satisfaction score of the patient being 5-7.&#xD;
&#xD;
      Hormonal stress response was assessed through recording plasma cortisol (micrograms / dl) 2&#xD;
      hours postoperatively. Serum cortisol was measured by a Fluorescence Polarization Immunoassay&#xD;
      Technology (FPIA) by the Abbott AXSYM system with the following reference ranges (morning&#xD;
      serum cortisol 4.2-38.4 ug/dl) and evening serum cortisol 1.7-16.6 ug/dl).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>to compare the analgesic efficacy of Dulox alone, with Dulox and Dex combination in reducing postoperative pain measured by total pethdine requirements 12h after gynecological surgeries.</measure>
    <time_frame>Total pethdine requirements 12h after gynecological surgeries.</time_frame>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Post Operative Pain Control</condition>
  <arm_group>
    <arm_group_label>group (I) (GI) (n=25)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>group (II) (GII) (n=25)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>group (III) (GIII) (control group) (n=25)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dulox capsule (60mg)</intervention_name>
    <description>each patient received Dulox capsule (60mg) orally with sips of water 2 hours preoperatively and 100 ml 0.9% sodium chloride solution (NS) intravenous infusion (IVI) over 15 min</description>
    <arm_group_label>group (I) (GI) (n=25)</arm_group_label>
    <other_name>Dulox was presented as CYMBALTA® capsules manufactured by Lilly del Caribe Inc.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>combined Dulox capsule (60 mg) orally and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI</intervention_name>
    <description>each patient received combined Dulox capsule (60 mg) orally with sips of water and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI over 15 min, 2 hours preoperatively</description>
    <arm_group_label>group (II) (GII) (n=25)</arm_group_label>
    <other_name>Dex was presented as dexamethasone sulphate ampoules 8mg in 2ml. (Medical Union Pharmaceutical, Egypt MUP)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>a placebo capsule identical to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone</intervention_name>
    <description>each patient received a placebo capsule identical to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone 2 hours preoperatively.</description>
    <arm_group_label>group (III) (GIII) (control group) (n=25)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        female patients aged between 25 and 35 years old of the American Society of&#xD;
        Anesthesiologists (ASA) physical status I and II scheduled for elective laparoscopic&#xD;
        gynecological surgeries (for infertility) under general anesthesia.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patient's refusal,&#xD;
&#xD;
          2. duration of surgery more than 90 minutes,&#xD;
&#xD;
          3. allergy to any drugs of the study,&#xD;
&#xD;
          4. smokers, history of drug or alcohol abuse,&#xD;
&#xD;
          5. treatment with antidepressants,&#xD;
&#xD;
          6. history of diabetes or epilepsy,&#xD;
&#xD;
          7. , history of chronic pain or daily intake of analgesics within 24 h before surgery,&#xD;
&#xD;
          8. treatment with systemic glucocorticoids within 4 weeks before surgery and (9) impaired&#xD;
             kidney or liver functions. -&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Dr.Ibrahim Mamdouh Esmat</investigator_full_name>
    <investigator_title>Lecturer of Anesthesia and Intensive Care Department, Faculty of Medicine, Ain- shams University, Cairo, Egypt.</investigator_title>
  </responsible_party>
  <keyword>Duloxetine, Dexamethasone, Postoperative pain, side effects.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03250494
org study id: 17585
nct id: NCT03250494
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
75 female patients were randomly allocated into one of three equal groups. Group I(GI)
      received Dulox 60 mg orally and 100 ml 0.9% sodium chloride solution (NS) intravenous
      infusion (IVI) over 15 min, group II(GII): received combined Dulox capsule 60 mg orally and
      Dex 0.1mg/kg mixed with 100 ml NS IVI and group III(GIII) received identical placebo
      duloxetine capsule and 100 ml NS IVI as a placebo for Dex, 2 hours preoperatively. Patients'
      vitals, VAS and sedation score were assessed at 30 minutes, 1h, 2 h, 6h and 12h
      postoperatively. Total pethidine requirements, plasma cortisol, PONV and patient's
      satisfaction were recorded.
This study was designed to be a randomized, placebo-controlled, double-blinded parallel study
      and this study was carried out at Ain-Shams university hospitals, from December 2014 to
      January2016, on 75 female patients aged between 25 and 35 years old of the American Society
      of Anesthesiologists (ASA) physical status I and II scheduled for elective laparoscopic
      gynecological surgeries (for infertility) under general anesthesia. Approval was obtained
      from the institutional ethical committee and written informed consent was obtained from all
      patients.

      Patients were not admitted to the study if any of the following criteria were present: (1)
      patient's refusal, (2) duration of surgery more than 90 minutes, (3) allergy to any drugs of
      the study, (4) smokers, history of drug or alcohol abuse, (5) treatment with antidepressants,
      (6) history of diabetes or epilepsy, (7) , history of chronic pain or daily intake of
      analgesics within 24 h before surgery, (8) treatment with systemic glucocorticoids within 4
      weeks before surgery and (9) impaired kidney or liver functions.

      Patients were randomly allocated into 3 equal groups, group (I) (GI) (n=25) each patient
      received Dulox capsule (60mg) orally with sips of water 2 hours preoperatively and 100 ml
      0.9% sodium chloride solution (NS) intravenous infusion (IVI) over 15 min (Placebo), group
      (II) (GII) (n=25) each patient received combined Dulox capsule (60 mg) orally with sips of
      water and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI over 15 min, 2 hours preoperatively and
      group (III) (GIII) (control group) (n=25) each patient received a placebo capsule identical
      to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone 2 hours
      preoperatively. Dulox was presented as CYMBALTA® capsules manufactured by Lilly del Caribe
      Inc. Imported by Elco and Dex was presented as dexamethasone sulphate ampoules 8mg in 2ml.
      (Medical Union Pharmaceutical, Egypt MUP). Randomization was done using computer-generated
      number table of random numbers in a 1:1 ratio and conducted using sequentially numbered,
      opaque and sealed envelope (SNOSE). Active Dulox capsules were indistinguishable from placebo
      capsules and placebo capsules contained starch. The study drugs were prepared by the hospital
      pharmacy and follow-up of patients was conducted by the anesthesia residents not involved in
      any other part of the study.

      During the preoperative anesthetic evaluation, patients were familiarized with 10 cm marked
      visual analogue scale (VAS) for PO assessment of pain, where 0 cm defines no pain and 10 cm
      defines the maximum intolerable pain. Patients were also assured that they would receive
      intramuscular injection (IM) of pethidine 0.5 mg / kg once they experienced pain
      postoperatively (patients with (VAS > 3).

      The general anesthesia technique was standardized for all the patients as well as monitors
      including 5 lead ECG, non- invasive blood pressure (NIBP) monitor, pulse oximetry and
      capnography after intubation using Datascope monitors. Neuromuscular function was monitored
      using a peripheral nerve stimulator. After establishing an intravenous (IV) line, induction
      of general anesthesia with fentanyl (2 ug/kg) and sleeping dose of propofol followed by
      rocuronium (0.6 mg/kg) to facilitate orotracheal intubation was done. Anesthesia was
      maintained using isoflurane in oxygen and air. Ranitidine (50 mg/ampoule) was given diluted
      in 10 ml 0.9% sodium chloride solution (NS) slowly (IV) over 10 minutes as a gastroprotective
      regimen. At the end of the surgery, the residual neuromuscular paralysis was antagonized with
      neostigmine (0.05 mg/kg) and atropine (0.01 mg/kg). After satisfactory recovery, patients
      were extubated and transferred to the post-anesthesia care unit (PACU) where they were
      monitored with ECG, NIBP and pulse oximetry.

      Assessment of patients' vitals (HR, MAP), arterial SpO2, sedation score, visual analog scale
      (VAS), the first analgesic requirement time and adverse effects (e.g. nausea, vomiting
      (PONV), pruritis) were done at 30 minutes, 1h, 2 h, 6h and 12h postoperatively.

      PO pain was evaluated at rest based on visual analogue scale, first time to ask for rescue
      analgesia and total pethidine requirements in 12 hours (mg) postoperatively were recorded.
      Assessment of sedation was according to sedation score (Ramsay sedation scale) (14).

      Hypotension was considered if there was 20% decrease below the baseline for MAP and was
      treated with IV bolus of ephedrine (3-6 mg). Bradycardia was considered if the heart rate <
      55 beats/min and was treated with IV atropine (0.01mg/kg). Respiratory depression was defined
      as a respiratory rate less than 10 breaths/min-1 or peripheral oxygen saturation less than
      95% and was treated with oxygen through a transparent face mask and the intermittent doses of
      IV naloxone (0.4 mg). IV granisetron (1mg) was given in case of vomiting or after 2
      successive episodes of nausea. Pruritus was evaluated with a 4-point scale (0=absent, 1=mild,
      2=moderate, 3=severe or requiring treatment), and patients with severe pruritus were treated
      with IV clemastine (TavegylR) (2 mg / ampoule).

      Patient's satisfaction was done by asking the patient to answer the question, 'How would you
      rate your experience after the surgery?' using a 7-point Likert verbal rating scale (15) and
      acceptable satisfaction score of the patient being 5-7.

      Hormonal stress response was assessed through recording plasma cortisol (micrograms / dl) 2
      hours postoperatively. Serum cortisol was measured by a Fluorescence Polarization Immunoassay
      Technology (FPIA) by the Abbott AXSYM system with the following reference ranges (morning
      serum cortisol 4.2-38.4 ug/dl) and evening serum cortisol 1.7-16.6 ug/dl).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: to compare the analgesic efficacy of Dulox alone, with Dulox and Dex combination in reducing postoperative pain measured by total pethdine requirements 12h after gynecological surgeries.
time frame: Total pethdine requirements 12h after gynecological surgeries.
arm group label: group (I) (GI) (n=25)
arm group type: Active Comparator
arm group label: group (II) (GII) (n=25)
arm group type: Active Comparator
arm group label: group (III) (GIII) (control group) (n=25)
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Dulox capsule (60mg)
description: each patient received Dulox capsule (60mg) orally with sips of water 2 hours preoperatively and 100 ml 0.9% sodium chloride solution (NS) intravenous infusion (IVI) over 15 min
arm group label: group (I) (GI) (n=25)
other name: Dulox was presented as CYMBALTA® capsules manufactured by Lilly del Caribe Inc.
intervention type: Drug
intervention name: combined Dulox capsule (60 mg) orally and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI
description: each patient received combined Dulox capsule (60 mg) orally with sips of water and Dex 0.1mg/kg diluted in 100 ml 0.9% NS IVI over 15 min, 2 hours preoperatively
arm group label: group (II) (GII) (n=25)
other name: Dex was presented as dexamethasone sulphate ampoules 8mg in 2ml. (Medical Union Pharmaceutical, Egypt MUP)
intervention type: Drug
intervention name: a placebo capsule identical to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone
description: each patient received a placebo capsule identical to Dulox capsule and 100 ml 0.9% NS IVI over 15 min, as a placebo for dexamethasone 2 hours preoperatively.
arm group label: group (III) (GIII) (control group) (n=25)
criteria: 
gender: Female
minimum age: 25 Years
maximum age: 35 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Dr.Ibrahim Mamdouh Esmat
investigator title: Lecturer of Anesthesia and Intensive Care Department, Faculty of Medicine, Ain- shams University, Cairo, Egypt.
mesh term: Pain, Postoperative
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: BB 1101