<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/NCT01707251</url>
  </required_header>
  <id_info>
    <org_study_id>2011_436</org_study_id>
    <nct_id>NCT01707251</nct_id>
  </id_info>
  <brief_title>Intravenous Ibuprofen for Laparoscopic Bariatric Surgery</brief_title>
  <official_title>Intravenous Ibuprofen for Laparoscopic Bariatric Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jacobi Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cumberland Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sagatech Electronics Inc, Alberta, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Jacobi Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objective of this study is to test hypothesis that IV ibuprofen decreases 24 hours&#xD;
      morphine requirement using IV PCA in patients after laparoscopic bariatric surgery. Secondary&#xD;
      objective is to determine if it decreases respiratory depression measured using RD, improves&#xD;
      area under curve (AUC) for pain scores at rest (AUCr) and with cough (AUCa) and pressure pain&#xD;
      threshold (PPT) (important for mobilization). Tertiary objective is to compare incidence of&#xD;
      nausea/vomiting, sedation, itching, blood transfusion, over sedation, urinary retention, GI&#xD;
      or surgical bleeding, renal dysfunction, time to clears and baseline activity in ibuprofen&#xD;
      and control groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators will recruit patients scheduled for laparoscopic bariatric surgery at Jacobi&#xD;
      Medical Center (100 patients with allowance for 20% drop-offs). Patients will be randomized&#xD;
      to IV Ibuprofen versus placebo to test if morphine usage can be decreased, pain control&#xD;
      improved, pressure pain thresholds increased and respiratory depression decreased.&#xD;
&#xD;
      Exclusion/withdrawal criteria:&#xD;
&#xD;
      Patients with history of ibuprofen or aspirin allergy, morphine allergy, opioid or&#xD;
      psychotropic medication use pre-operatively, patients who would show positive preoperative&#xD;
      U-tox screening, patients unable to sign consent and patients unable to understand or use&#xD;
      patient controlled analgesia (PCA) or report pain intensity will be excluded. Patients with&#xD;
      GFR&lt;60 or history of GI bleed within 6 weeks will be excluded. Patients will be withdrawn&#xD;
      from the study if PCA would have to be discontinued, or the patient would develop acute renal&#xD;
      failure, GI bleed or post-surgical bleed. Intention to treat analysis will be performed&#xD;
      including the dropouts.&#xD;
&#xD;
      Patients' instructions and protocol:&#xD;
&#xD;
      Patients consented for the study will be educated about morphine PCA for pain control and&#xD;
      about pain reporting using NRS-11 and VAS scale at rest and with cough or during incentive&#xD;
      spirometry. They will receive instructions about Remmers Sleep Recorder (SagaTech Calgary,&#xD;
      Alberta, Canada), which includes continuous oximetry, and device will be provided for&#xD;
      overnight home screening preoperatively {Whitelaw,W.A. 2005;}. The sleep recorder data will&#xD;
      be reviewed pre-operatively and patients with respiratory disturbance index (RDI, measured as&#xD;
      oxygen desaturation event) &gt;15/hour who do not have OSA diagnosis and do not use CPAP will be&#xD;
      referred for sleep study and/or CPAP titration before the surgery, Patients will be educated&#xD;
      on QST testing using pressure algometry with 1cm2 padded tip {Coronado 2010} and will be&#xD;
      given survey questionnaire (postoperative diary) for self-reporting of pain (VAS at rest and&#xD;
      with cough), nausea/vomiting, activity and side effects from medications as well as&#xD;
      satisfaction with recovery and pain control. Baseline pressure pain thresholds (N/cm2) will&#xD;
      be tested at abdomen (area of postoperative hyperalgesia) and the pulp of third finger finger&#xD;
      on the right (reference site) using average of three measurements per site.&#xD;
&#xD;
      On the day of surgery patients will be allocated to group A or B according to&#xD;
      randomization.com generated table for two groups with variable blocking factor. Group A and B&#xD;
      assignment to the ibuprofen versus control will be available to the pharmacy only until the&#xD;
      completion of the study and statistical analysis.&#xD;
&#xD;
      The pharmacy will store Ibuprofen and on the day of surgery will provide the covered bag of&#xD;
      ibuprofen 800mg versus saline solution labeled with the patient's name .Group assignment (A&#xD;
      or B) will be known to the pharmacy only. IV will be started and first dose of medication&#xD;
      will be given over 5-30 minutes preoperatively. In the subgroup of patients, where surgery&#xD;
      start time is delayed by one hour or more, PPT will be repeated before the start of the&#xD;
      surgery.&#xD;
&#xD;
      Patients will have standardized general anesthetic for the surgery. Intraoperative opioid&#xD;
      usage will be recorded. Laparoscopic ports will be infiltrated with local anesthetic.&#xD;
&#xD;
      800mg Ibuprofen or placebo infusion will be repeated every 6 hours for 24 hours&#xD;
      postoperatively.&#xD;
&#xD;
      In recovery room patients will be started on morphine patient controlled analgesia (morphine&#xD;
      PCA 0.5mg every 5 minutes while NPO, with ability to escalate the dose up to 1 mg every&#xD;
      5minutes per hospital PCA protocol if patient requires additional morphine rescue to control&#xD;
      the pain, uses PCA appropriately and demonstrates no side effects). Patients will have&#xD;
      antiemetics and morphine loading/rescue dose (4mg Q15minute max 16mg per PACU nurse&#xD;
      discretion) per standard hospital protocol. Patients will be continuously monitored overnight&#xD;
      per nursing protocol and in addition to that with Remmer's unit (pulse oximetry, respiratory&#xD;
      effort, respiratory flow, airway pressure). Pain score at rest and with cough and&#xD;
      nausea/vomiting will be assessed periodically and will be reported by patient in the&#xD;
      postoperative diary. Pain scores will be integrated separately over 24 hours to obtain area&#xD;
      under curve at rest (AUCr) and with cough or activity (AUCa) Overnight oximetry recordings&#xD;
      will be analyzed post hoc to determine RDI. Patients with PCA will be monitored per hospital&#xD;
      policy (Q1h x 12h, then Q2hx 12h). All bariatric patients are continuously monitored&#xD;
      overnight in the PACU or surgical step-down unit. Nurses taking care of the patient routinely&#xD;
      notify anesthesia and/or surgical team about significant apnea/hypopnea.&#xD;
&#xD;
      PCA usage log will be obtained from the pump and morphine given by the nurses will be added&#xD;
      to calculate postoperative morphine cumulative dose for 24 hours. If PCA is discontinued,&#xD;
      patient data will be analyzed as drop-off. Per hospital PCA policy in the event of excessive&#xD;
      sedation and/or respiratory depression (level of sedation 4) following actions are to be&#xD;
      taken:&#xD;
&#xD;
        -  STOP PCA PUMP, stimulate patient, support respirations with bag valve mask as needed&#xD;
&#xD;
        -  Have a coworker notify the Rapid Response Team. Arrange for BMV, O2, and suction.&#xD;
&#xD;
        -  Hang Naloxone 0.8mg in 100ml 0.9% NS IVSS -continue until respirations are more than 9&#xD;
           b/m or a total of 0.8mg is infused.&#xD;
&#xD;
      Time 0 for the purposes of study will be time of admission to PACU. PPT will be tested in the&#xD;
      PACU in the subset of patients who are awake and wiling to perform QST testing, when their&#xD;
      pain is controlled with NRS&lt;=4. QST will be repeated in qualifying patients (awake, pain&#xD;
      controlled) following day.&#xD;
&#xD;
      In addition investigators will record:&#xD;
&#xD;
        1. Transfusion requirement (number of units)&#xD;
&#xD;
        2. Difference between pre-operative and discharge hemoglobin&#xD;
&#xD;
        3. Requirement for surgical revision due to anastomotic leak&#xD;
&#xD;
        4. Incidence of wound infection&#xD;
&#xD;
        5. Readmission rate within 30 days&#xD;
&#xD;
        6. Preoperative and discharge GFR&#xD;
&#xD;
        7. Timed NRS-11 (nurse recorded) and VAS (self reported) for pain at rest and during cough&#xD;
           or incentive spirometry.&#xD;
&#xD;
        8. Area under the curve AUCr using NRS at rest and during incentive spirometry/cough&#xD;
           (AUCa). AUCr and AUCa will be separately integrated to area under curve for 24 hours.&#xD;
&#xD;
        9. Total dose of morphine given by nurses for 24 hours.&#xD;
&#xD;
       10. Morphine PCA usage (hourly and cumulative/24h)&#xD;
&#xD;
       11. Presence of nausea/vomiting for 24 hours&#xD;
&#xD;
       12. Antiemetic requirement (number of doses).&#xD;
&#xD;
       13. Time to oral tolerance (clears, solids) (hours)&#xD;
&#xD;
       14. Time to bowel movement (hours)&#xD;
&#xD;
       15. Time patient meets discharge criteria from the PACU (hours)&#xD;
&#xD;
       16. Time to discharge from PACU (hours)&#xD;
&#xD;
       17. Time to discharge from hospital (hours)&#xD;
&#xD;
       18. Respiratory disturbance index) baseline and postoperatively (from Remmers unit)&#xD;
&#xD;
       19. Incidence of desaturation to SpO2&lt;95, &lt;90 and &lt;80% baseline and postoperatively (from&#xD;
           Remmers unit). Maximum FiO2 required postoperatively (excluding first 2 hours&#xD;
           immediately after surgery).&#xD;
&#xD;
       20. Incidence of over sedation (sedation score 3 and 4)&#xD;
&#xD;
       21. Naloxone requirement if any&#xD;
&#xD;
       22. Patient satisfaction scores&#xD;
&#xD;
       23. Time to out of bed to chair (hours)&#xD;
&#xD;
       24. Time to stand-up (hours)&#xD;
&#xD;
       25. Time to ambulation (hours)&#xD;
&#xD;
       26. Time to baseline physical activity (days)&#xD;
&#xD;
       27. Max temperature&#xD;
&#xD;
       28. Incidence of DVT&#xD;
&#xD;
       29. Reason for delayed discharge (&gt;72 hours)&#xD;
&#xD;
       30. Incidence of readmission within 4 weeks&#xD;
&#xD;
       31. Incidence of reoperation within 4 weeks&#xD;
&#xD;
      Data will be analyzed using commercially available statistical software.&#xD;
&#xD;
      If dropouts to the study will be present, intent to treat analysis will be performed.&#xD;
&#xD;
      Metric scale data will be tested for normality of distribution (Kolmogorov-Smirnov test).&#xD;
      Categorical data will be presented as absolute frequency and relative distribution. For&#xD;
      normally distributed data, a t test for independent samples will be used to compare pre/post&#xD;
      differences between the treatment groups. Otherwise, a nonparametric Mann-Whitney test will&#xD;
      be used. Categorical data will be compared using chi square test or Fisher exact test for&#xD;
      groups &lt;5. Bonferonni correction will be done for multiple comparisons.&#xD;
&#xD;
      After comparing groups for age, sex, BMI, co morbidities, surgical time, baseline pressure&#xD;
      pain thresholds investigators will investigate whether assignment into ibuprofen or saline&#xD;
      groups makes a difference In the primary, secondary and tertiary outcomes.&#xD;
&#xD;
      Our null hypothesis (H0) is that there will be no differences in cumulative 24h morphine&#xD;
      consumption, AUCa and AUCr for pain scores, and that there will be no change in pre/post&#xD;
      difference in RDI and pressure pain thresholds. In addition investigators hypothesize that&#xD;
      there will be no difference in the incidence of nausea/vomiting, discharge readiness, patient&#xD;
      satisfaction among the test and control groups&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>24 hours postoperative morphine requirement using IV PCA</measure>
    <time_frame>24 hours</time_frame>
    <description>Will test if IV ibuprofen decrease postoperative morphine requirement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Respiratory depression</measure>
    <time_frame>24 hours postoperative</time_frame>
    <description>Compare respiratory disturbance index preoperatively versus postoperatively and incidence of hypoxia (SpO2 &lt;95, &lt;90 and &lt;80%) in ibuprofen and placebo groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain scores</measure>
    <time_frame>24 hours postoperatively</time_frame>
    <description>Area under curve for pain scores at rest (AUCr) and with cough (AUCa).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure pain thresholds</measure>
    <time_frame>24 hours</time_frame>
    <description>Preoperative versus postoperative pressure pain threshold (PPT) will be measured to assess effect of ibuprofen on PPT (important for mobilization).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Nausea/vomiting</measure>
    <time_frame>24 hours</time_frame>
    <description>Compare incidence of nausea vomiting between groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfusion requirement</measure>
    <time_frame>3 days</time_frame>
    <description>Compare incidence of blood transfusions between groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Urinary retention</measure>
    <time_frame>3 days</time_frame>
    <description>Incidence of recatheterization after foley removal between groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Surgical bleeding</measure>
    <time_frame>30 days</time_frame>
    <description>Incidence of reoperation for bleeding in ibuprofen and control groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of renal dysfunction</measure>
    <time_frame>3 days</time_frame>
    <description>Compare preoperative versus discharge GFR in ibuprofen and control groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to oral intake</measure>
    <time_frame>3 days</time_frame>
    <description>Time to clears in ibuprofen and control groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Return of baseline activity</measure>
    <time_frame>30 days</time_frame>
    <description>Time to baseline activity in ibuprofen and control groups</description>
  </other_outcome>
  <other_outcome>
    <measure>Time patient meets discharge criteria from the PACU (hours)</measure>
    <time_frame>24 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to discharge from PACU (hours)</measure>
    <time_frame>24 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to discharge from hospital (hours)</measure>
    <time_frame>1 week</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to ambulation (hours)</measure>
    <time_frame>3 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of readmission within 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of reoperation within 4 weeks</measure>
    <time_frame>4 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of DVT</measure>
    <time_frame>30 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Max temperature</measure>
    <time_frame>3 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to oral tolerance (clears, solids) (hours)</measure>
    <time_frame>3 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Antiemetic requirement (number of doses)</measure>
    <time_frame>24 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to bowel movement (hours)</measure>
    <time_frame>1 week</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of over sedation (sedation score 3 and 4)</measure>
    <time_frame>24 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Naloxone requirement</measure>
    <time_frame>24 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Patient satisfaction scores</measure>
    <time_frame>30 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to out of bed to chair (hours)</measure>
    <time_frame>3 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to stand-up (hours)</measure>
    <time_frame>3 days</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Intravenous Ibuprofen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>800 mg Ibuprofen IV every 6 hours starting preoperatively (5 doses).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>IV saline every 6 hours starting preoperatively (5 doses).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous Ibuprofen</intervention_name>
    <description>800 mg Ibuprofen IV every 6 hours starting preoperatively (5 doses).</description>
    <arm_group_label>Intravenous Ibuprofen</arm_group_label>
    <other_name>Caldorol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Placebo control</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients scheduled for laparoscopic bariatric surgery at Jacobi Medical Center&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with history of ibuprofen or aspirin allergy&#xD;
&#xD;
          -  morphine allergy&#xD;
&#xD;
          -  opioid or psychotropic medication use pre-operatively&#xD;
&#xD;
          -  positive preoperative U-tox screening&#xD;
&#xD;
          -  unable to sign consent and patients unable to understand or use patient controlled&#xD;
             analgesia (PCA) or report pain intensity&#xD;
&#xD;
          -  GFR &lt;60 or history of GI bleed within 6 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mindaugas Pranevicius, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jacobi Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jacobi Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>September 2, 2015</last_update_submitted>
  <last_update_submitted_qc>September 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Jacobi Medical Center</investigator_affiliation>
    <investigator_full_name>Mindaugas Pranevicius</investigator_full_name>
    <investigator_title>Attending Anesthesiologist, Director of Pain Medicine</investigator_title>
  </responsible_party>
  <keyword>Obesity, Morbid</keyword>
  <keyword>Bariatric Surgery</keyword>
  <keyword>Laparoscopy</keyword>
  <keyword>Intravenous Ibuprofen</keyword>
  <keyword>Analgesia</keyword>
  <keyword>Morphine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</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/NCT01707251
org study id: 2011_436
nct id: NCT01707251
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Primary objective of this study is to test hypothesis that IV ibuprofen decreases 24 hours
      morphine requirement using IV PCA in patients after laparoscopic bariatric surgery. Secondary
      objective is to determine if it decreases respiratory depression measured using RD, improves
      area under curve (AUC) for pain scores at rest (AUCr) and with cough (AUCa) and pressure pain
      threshold (PPT) (important for mobilization). Tertiary objective is to compare incidence of
      nausea/vomiting, sedation, itching, blood transfusion, over sedation, urinary retention, GI
      or surgical bleeding, renal dysfunction, time to clears and baseline activity in ibuprofen
      and control groups.
Investigators will recruit patients scheduled for laparoscopic bariatric surgery at Jacobi
      Medical Center (100 patients with allowance for 20% drop-offs). Patients will be randomized
      to IV Ibuprofen versus placebo to test if morphine usage can be decreased, pain control
      improved, pressure pain thresholds increased and respiratory depression decreased.

      Exclusion/withdrawal criteria:

      Patients with history of ibuprofen or aspirin allergy, morphine allergy, opioid or
      psychotropic medication use pre-operatively, patients who would show positive preoperative
      U-tox screening, patients unable to sign consent and patients unable to understand or use
      patient controlled analgesia (PCA) or report pain intensity will be excluded. Patients with
      GFR<60 or history of GI bleed within 6 weeks will be excluded. Patients will be withdrawn
      from the study if PCA would have to be discontinued, or the patient would develop acute renal
      failure, GI bleed or post-surgical bleed. Intention to treat analysis will be performed
      including the dropouts.

      Patients' instructions and protocol:

      Patients consented for the study will be educated about morphine PCA for pain control and
      about pain reporting using NRS-11 and VAS scale at rest and with cough or during incentive
      spirometry. They will receive instructions about Remmers Sleep Recorder (SagaTech Calgary,
      Alberta, Canada), which includes continuous oximetry, and device will be provided for
      overnight home screening preoperatively {Whitelaw,W.A. 2005;}. The sleep recorder data will
      be reviewed pre-operatively and patients with respiratory disturbance index (RDI, measured as
      oxygen desaturation event) >15/hour who do not have OSA diagnosis and do not use CPAP will be
      referred for sleep study and/or CPAP titration before the surgery, Patients will be educated
      on QST testing using pressure algometry with 1cm2 padded tip {Coronado 2010} and will be
      given survey questionnaire (postoperative diary) for self-reporting of pain (VAS at rest and
      with cough), nausea/vomiting, activity and side effects from medications as well as
      satisfaction with recovery and pain control. Baseline pressure pain thresholds (N/cm2) will
      be tested at abdomen (area of postoperative hyperalgesia) and the pulp of third finger finger
      on the right (reference site) using average of three measurements per site.

      On the day of surgery patients will be allocated to group A or B according to
      randomization.com generated table for two groups with variable blocking factor. Group A and B
      assignment to the ibuprofen versus control will be available to the pharmacy only until the
      completion of the study and statistical analysis.

      The pharmacy will store Ibuprofen and on the day of surgery will provide the covered bag of
      ibuprofen 800mg versus saline solution labeled with the patient's name .Group assignment (A
      or B) will be known to the pharmacy only. IV will be started and first dose of medication
      will be given over 5-30 minutes preoperatively. In the subgroup of patients, where surgery
      start time is delayed by one hour or more, PPT will be repeated before the start of the
      surgery.

      Patients will have standardized general anesthetic for the surgery. Intraoperative opioid
      usage will be recorded. Laparoscopic ports will be infiltrated with local anesthetic.

      800mg Ibuprofen or placebo infusion will be repeated every 6 hours for 24 hours
      postoperatively.

      In recovery room patients will be started on morphine patient controlled analgesia (morphine
      PCA 0.5mg every 5 minutes while NPO, with ability to escalate the dose up to 1 mg every
      5minutes per hospital PCA protocol if patient requires additional morphine rescue to control
      the pain, uses PCA appropriately and demonstrates no side effects). Patients will have
      antiemetics and morphine loading/rescue dose (4mg Q15minute max 16mg per PACU nurse
      discretion) per standard hospital protocol. Patients will be continuously monitored overnight
      per nursing protocol and in addition to that with Remmer's unit (pulse oximetry, respiratory
      effort, respiratory flow, airway pressure). Pain score at rest and with cough and
      nausea/vomiting will be assessed periodically and will be reported by patient in the
      postoperative diary. Pain scores will be integrated separately over 24 hours to obtain area
      under curve at rest (AUCr) and with cough or activity (AUCa) Overnight oximetry recordings
      will be analyzed post hoc to determine RDI. Patients with PCA will be monitored per hospital
      policy (Q1h x 12h, then Q2hx 12h). All bariatric patients are continuously monitored
      overnight in the PACU or surgical step-down unit. Nurses taking care of the patient routinely
      notify anesthesia and/or surgical team about significant apnea/hypopnea.

      PCA usage log will be obtained from the pump and morphine given by the nurses will be added
      to calculate postoperative morphine cumulative dose for 24 hours. If PCA is discontinued,
      patient data will be analyzed as drop-off. Per hospital PCA policy in the event of excessive
      sedation and/or respiratory depression (level of sedation 4) following actions are to be
      taken:

        -  STOP PCA PUMP, stimulate patient, support respirations with bag valve mask as needed

        -  Have a coworker notify the Rapid Response Team. Arrange for BMV, O2, and suction.

        -  Hang Naloxone 0.8mg in 100ml 0.9% NS IVSS -continue until respirations are more than 9
           b/m or a total of 0.8mg is infused.

      Time 0 for the purposes of study will be time of admission to PACU. PPT will be tested in the
      PACU in the subset of patients who are awake and wiling to perform QST testing, when their
      pain is controlled with NRS<=4. QST will be repeated in qualifying patients (awake, pain
      controlled) following day.

      In addition investigators will record:

        1. Transfusion requirement (number of units)

        2. Difference between pre-operative and discharge hemoglobin

        3. Requirement for surgical revision due to anastomotic leak

        4. Incidence of wound infection

        5. Readmission rate within 30 days

        6. Preoperative and discharge GFR

        7. Timed NRS-11 (nurse recorded) and VAS (self reported) for pain at rest and during cough
           or incentive spirometry.

        8. Area under the curve AUCr using NRS at rest and during incentive spirometry/cough
           (AUCa). AUCr and AUCa will be separately integrated to area under curve for 24 hours.

        9. Total dose of morphine given by nurses for 24 hours.

       10. Morphine PCA usage (hourly and cumulative/24h)

       11. Presence of nausea/vomiting for 24 hours

       12. Antiemetic requirement (number of doses).

       13. Time to oral tolerance (clears, solids) (hours)

       14. Time to bowel movement (hours)

       15. Time patient meets discharge criteria from the PACU (hours)

       16. Time to discharge from PACU (hours)

       17. Time to discharge from hospital (hours)

       18. Respiratory disturbance index) baseline and postoperatively (from Remmers unit)

       19. Incidence of desaturation to SpO2<95, <90 and <80% baseline and postoperatively (from
           Remmers unit). Maximum FiO2 required postoperatively (excluding first 2 hours
           immediately after surgery).

       20. Incidence of over sedation (sedation score 3 and 4)

       21. Naloxone requirement if any

       22. Patient satisfaction scores

       23. Time to out of bed to chair (hours)

       24. Time to stand-up (hours)

       25. Time to ambulation (hours)

       26. Time to baseline physical activity (days)

       27. Max temperature

       28. Incidence of DVT

       29. Reason for delayed discharge (>72 hours)

       30. Incidence of readmission within 4 weeks

       31. Incidence of reoperation within 4 weeks

      Data will be analyzed using commercially available statistical software.

      If dropouts to the study will be present, intent to treat analysis will be performed.

      Metric scale data will be tested for normality of distribution (Kolmogorov-Smirnov test).
      Categorical data will be presented as absolute frequency and relative distribution. For
      normally distributed data, a t test for independent samples will be used to compare pre/post
      differences between the treatment groups. Otherwise, a nonparametric Mann-Whitney test will
      be used. Categorical data will be compared using chi square test or Fisher exact test for
      groups <5. Bonferonni correction will be done for multiple comparisons.

      After comparing groups for age, sex, BMI, co morbidities, surgical time, baseline pressure
      pain thresholds investigators will investigate whether assignment into ibuprofen or saline
      groups makes a difference In the primary, secondary and tertiary outcomes.

      Our null hypothesis (H0) is that there will be no differences in cumulative 24h morphine
      consumption, AUCa and AUCr for pain scores, and that there will be no change in pre/post
      difference in RDI and pressure pain thresholds. In addition investigators hypothesize that
      there will be no difference in the incidence of nausea/vomiting, discharge readiness, patient
      satisfaction among the test and control groups
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 24 hours postoperative morphine requirement using IV PCA
time frame: 24 hours
description: Will test if IV ibuprofen decrease postoperative morphine requirement.
measure: Respiratory depression
time frame: 24 hours postoperative
description: Compare respiratory disturbance index preoperatively versus postoperatively and incidence of hypoxia (SpO2 <95, <90 and <80%) in ibuprofen and placebo groups.
measure: Pain scores
time frame: 24 hours postoperatively
description: Area under curve for pain scores at rest (AUCr) and with cough (AUCa).
measure: Pressure pain thresholds
time frame: 24 hours
description: Preoperative versus postoperative pressure pain threshold (PPT) will be measured to assess effect of ibuprofen on PPT (important for mobilization).
measure: Nausea/vomiting
time frame: 24 hours
description: Compare incidence of nausea vomiting between groups.
measure: Transfusion requirement
time frame: 3 days
description: Compare incidence of blood transfusions between groups.
measure: Urinary retention
time frame: 3 days
description: Incidence of recatheterization after foley removal between groups.
measure: Surgical bleeding
time frame: 30 days
description: Incidence of reoperation for bleeding in ibuprofen and control groups.
measure: Incidence of renal dysfunction
time frame: 3 days
description: Compare preoperative versus discharge GFR in ibuprofen and control groups.
measure: Time to oral intake
time frame: 3 days
description: Time to clears in ibuprofen and control groups.
measure: Return of baseline activity
time frame: 30 days
description: Time to baseline activity in ibuprofen and control groups
measure: Time patient meets discharge criteria from the PACU (hours)
time frame: 24 hours
measure: Time to discharge from PACU (hours)
time frame: 24 hours
measure: Time to discharge from hospital (hours)
time frame: 1 week
measure: Time to ambulation (hours)
time frame: 3 days
measure: Incidence of readmission within 4 weeks
time frame: 4 weeks
measure: Incidence of reoperation within 4 weeks
time frame: 4 weeks
measure: Incidence of DVT
time frame: 30 days
measure: Max temperature
time frame: 3 days
measure: Time to oral tolerance (clears, solids) (hours)
time frame: 3 days
measure: Antiemetic requirement (number of doses)
time frame: 24 hours
measure: Time to bowel movement (hours)
time frame: 1 week
measure: Incidence of over sedation (sedation score 3 and 4)
time frame: 24 hours
measure: Naloxone requirement
time frame: 24 hours
measure: Patient satisfaction scores
time frame: 30 days
measure: Time to out of bed to chair (hours)
time frame: 3 days
measure: Time to stand-up (hours)
time frame: 3 days
arm group label: Intravenous Ibuprofen
arm group type: Experimental
description: 800 mg Ibuprofen IV every 6 hours starting preoperatively (5 doses).
arm group label: Saline
arm group type: Placebo Comparator
description: IV saline every 6 hours starting preoperatively (5 doses).
intervention type: Drug
intervention name: Intravenous Ibuprofen
description: 800 mg Ibuprofen IV every 6 hours starting preoperatively (5 doses).
arm group label: Intravenous Ibuprofen
other name: Caldorol
intervention type: Drug
intervention name: Saline
description: Placebo control
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mindaugas Pranevicius, MD
role: Principal Investigator
affiliation: Jacobi Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Jacobi Medical Center
investigator full name: Mindaugas Pranevicius
investigator title: Attending Anesthesiologist, Director of Pain Medicine
mesh term: Obesity
mesh term: Ibuprofen