<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/NCT03824808</url>
  </required_header>
  <id_info>
    <org_study_id>2012402</org_study_id>
    <nct_id>NCT03824808</nct_id>
  </id_info>
  <brief_title>Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery</brief_title>
  <official_title>A Prospective, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Evaluating the Use of Perioperative Intravenous Lidocaine Infusion to Decrease Pain Scores and Opioid Consumption After Robotic-Assisted Prostatectomy and Robotic-Assisted Partial Nephrectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</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>
      Controlling pain is fundamental during and after surgical procedures. This study examines&#xD;
      pain associated with robotic assisted surgery on prostate cancer or a kidney mass. In recent&#xD;
      years, the risk of opioids in the postoperative period has gained interest due to the growing&#xD;
      epidemic of addiction, dependence, and overdose. In this study, the investigators expect a&#xD;
      continuous infusion of intravenous lidocaine during the perioperative period to result in&#xD;
      less pain and less opioid use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, the risk of opioids in the post-operative period has gained interest due to&#xD;
      the growing epidemic of addiction, dependence, and overdose. The rate of drug overdose&#xD;
      secondary to opioids has continued to increase at an alarming rate. This has been a primary&#xD;
      point of concern in all fields of medicine and Urology has not been an exception. This is&#xD;
      also a nationwide government and public health concern. This has generated an increased focus&#xD;
      on the use of non-opioid analgesics after surgery such as intravenous lidocaine.&#xD;
&#xD;
      Opioids remain the primary source of relief for postoperative pain and have the potential to&#xD;
      lead to significant morbidity. Opioids may delay recovery following surgery and have many&#xD;
      well-known adverse effects including, but not limited to, nausea, vomiting and prolonged&#xD;
      post-operative ileus. Furthermore, in one study, they inadequately provided pain control in&#xD;
      50-60% of postoperative participants. This is a frequent report of participants because of&#xD;
      the less than optimal utilization of the medications in fear of their dose dependent adverse&#xD;
      effects and various contraindications. On the other hand, surplus medication following&#xD;
      surgery is another prominent component of the opioid problem in Urologic practices. Bates et&#xD;
      al. found that of the 586 participants that underwent a urological procedure that they&#xD;
      reviewed, 67% of them had collected surplus medication. It is both necessary and beneficial&#xD;
      for surgeons and participants to utilize dose-sparing strategies following surgery to&#xD;
      decrease overall opioid usage and outpatient requirement.&#xD;
&#xD;
      One mechanism that has already been employed for overall improvement in prostatectomies and&#xD;
      partial nephrectomies is the use of the robotic assisted approach. Robot assisted partial&#xD;
      nephrectomies (RALPN) and robotic assisted laparoscopic prostatectomies (RALP) are becoming a&#xD;
      mainstay in urologic surgery and increasing annually. This coincides with a continuous&#xD;
      downward trend of laparoscopic and open urologic procedures. RALPN has been shown in a&#xD;
      meta-analysis to be more favorable than laparoscopic partial nephrectomies and will continue&#xD;
      to be the surgical procedure of choice in the near future. RALP is also now the dominant&#xD;
      surgical approach while open and laparoscopic prostatectomies becoming less frequent. Robotic&#xD;
      assisted surgery is associated with improved functional outcomes, pain scores, shorter&#xD;
      hospital stays, and increases in participants satisfaction in many studies.&#xD;
&#xD;
      While there has been a pronounced increase in robotic surgery over the past 10 years that has&#xD;
      demonstrated benefits for participants, there has been limited studies regarding the pain&#xD;
      management for these participants. Robotic assisted surgery itself decreases pain levels&#xD;
      compared to other approaches, but participants continue to experience mild to moderate pain&#xD;
      levels in the postoperative period, which are classically managed with NSAIDs and opioids.&#xD;
&#xD;
      Recently, Enhanced Recovery after Surgery protocols (ERAS) have been implemented in an&#xD;
      attempt to decrease pain and opioid use as one outcome. ERAS utilizes multimodal analgesia&#xD;
      and has shown improvement of participant satisfaction and perioperative opioid use. Systemic&#xD;
      lidocaine is becoming more popular and regularly applied through this protocol and, other&#xD;
      practices, in due to its analgesic, anti-hyperalgesia and anti-inflammatory properties that&#xD;
      it contains. Systemic lidocaine mechanism of action is not fully understood, but it appears&#xD;
      to be multifaceted. Systemic lidocaine inhibits voltage-gated sodium channels in both the&#xD;
      peripheral and central nervous system. This is believed to cause an additive effect when&#xD;
      combined with inhaled anesthetics which also work on the voltage-gated sodium channels in the&#xD;
      central nervous system. Despite this summative effect, this is likely not the primary&#xD;
      mechanism of action. Instead, it is believed to predominantly act on anti-inflammatory&#xD;
      signaling and through inhibiting neuronal effects. Additionally, it reduces nociception and&#xD;
      cardiovascular response to surgical stress and pain.&#xD;
&#xD;
      This is a prospective, randomized, double-blinded, placebo-controlled clinical trial on&#xD;
      lidocaine infusion for pain control and opioid consumption in participants undergoing either&#xD;
      robotic-assisted laparoscopic prostatectomy or robotic-assisted laparoscopic partial&#xD;
      nephrectomy at University of Missouri Hospital. Participants will be randomized in a 1:1&#xD;
      fashion and stratified by the type of surgery to receive a perioperative intravenous 0.8%&#xD;
      lidocaine infusion at 1 mg/kg/h if &lt; age 65 and 0.5 mg/kg/h if ≥ age 65 or an equal volume&#xD;
      and rate of normal saline as a placebo. The infusion will be started 15 minutes after&#xD;
      endotracheal intubation and continue for 24 hours.&#xD;
&#xD;
      The study that the investigators propose targets an area of urology that is underrepresented&#xD;
      in the current literature despite its increasing importance. To the best of the&#xD;
      investigator's knowledge, this has not been directly studied before, although it has been&#xD;
      utilized numerous times in the ERAS protocol at the University of Missouri Hospital&#xD;
      throughout the Division of Urology and Anesthesiology &amp; Perioperative Medicine in&#xD;
      participants undergoing robotic surgery. The benefits of intravenous lidocaine have been&#xD;
      demonstrated in other areas and these results warrant a prospective, randomized,&#xD;
      double-blinded, placebo controlled study to assess the lidocaine infusion effects for robot&#xD;
      assisted laparoscopic prostatectomies and partial nephrectomies. As the number of robotic&#xD;
      assisted surgeries and emphasis on opioid reduction continues, the evaluation of systemic&#xD;
      lidocaine will be important in improving outcomes in urology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Challenges with recruitment of surgical research subjects in the target population.&#xD;
  </why_stopped>
  <start_date type="Actual">February 26, 2019</start_date>
  <completion_date type="Actual">March 26, 2020</completion_date>
  <primary_completion_date type="Actual">March 26, 2020</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>Participants will receive either intraoperative 0.8% lidocaine or normal saline at 1 mg/kg/h when younger than 65 years and 0.5 mg/kg/h when greater than or equal to the age of 65 to be delivered by continuous infusion for 24 hours.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The surgeon, anesthesiologist, operating room staff, participant, personnel in the postanesthesia care unit (PACU) as well as the investigators collecting the postoperative data will be blinded to the group allocation. Study medication is prepared and masked by an unblinded investigation drug pharmacist who is not involved in clinical care.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in post-operative pain scores measured by Visual Analog Scale</measure>
    <time_frame>Through study completion, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>10-cm Visual Analog Scale (VAS), score of 0 &quot;no pain&quot; to a score of 10 &quot;worst pain ever&quot;</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Opioid consumption</measure>
    <time_frame>Through study completion, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in opioid consumption in first 24 hours, discharge and 14 days post-operatively (morphine equivalents)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>At participant discharge, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in length of hospital stay determined by surgeon excluding social factors that may delay discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of post-operative Ileus</measure>
    <time_frame>During hospitalization, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in post-operative Ileus duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative PACU time</measure>
    <time_frame>During hospitalization, approximately 2 hours post-surgery</time_frame>
    <description>Difference in time in the Post Anesthesia Care Unit (PACU) after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Return of flatus</measure>
    <time_frame>During hospitalization, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in return of flatus after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to out of bed</measure>
    <time_frame>During hospitalization, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in time to out of bed to chair after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>First ambulation in the hallway</measure>
    <time_frame>During hospitalization, assessed up to 14 days (+/-) 7 days</time_frame>
    <description>Difference in time to first ambulation in the hallway after surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Kidney Cancer</condition>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% Sodium Chloride Injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution</intervention_name>
    <description>Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection.</description>
    <arm_group_label>Treatment group</arm_group_label>
    <other_name>Lidocaine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% Sodium Chloride Injection</intervention_name>
    <description>Sodium Chloride Injection USP is sterile, nonpyrogenic, isotonic and contains no bacteriostatic or antimicrobial agents.</description>
    <arm_group_label>Control group</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Undergoing robotic assisted prostatectomy or robotic assisted partial nephrectomy at&#xD;
             University of Missouri Hospital for prostate cancer or kidney mass&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ASA I-III&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to obtain written informed consent&#xD;
&#xD;
          -  Allergy to lidocaine or other amide local anesthetics&#xD;
&#xD;
          -  Atrioventricular conduction blocks&#xD;
&#xD;
          -  CV instability and concomitant use of alpha agonists or beta blockers&#xD;
&#xD;
          -  Recent myocardial infarction (≤ 6 months ago)&#xD;
&#xD;
          -  Cardiac arrhythmia disorders&#xD;
&#xD;
          -  Stokes-Adams syndrome&#xD;
&#xD;
          -  Wolff-Parkinson-White syndrome&#xD;
&#xD;
          -  Seizure disorders&#xD;
&#xD;
          -  Liver failure or hepatic dysfunction&#xD;
&#xD;
          -  Significant renal disease with a serum creatinine ≥ 2 mg/dl&#xD;
&#xD;
          -  A family history of malignant hyperthermia&#xD;
&#xD;
          -  Current use of opioids or documented history of opioid abuse&#xD;
&#xD;
          -  Typically, have less than 3 bowel movement per week&#xD;
&#xD;
          -  Combined surgical cases that include robotic prostatectomy or robotic partial&#xD;
             nephrectomy&#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>Boris Mraovic, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bates C, Laciak R, Southwick A, Bishoff J. Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 2011 Feb;185(2):551-5. doi: 10.1016/j.juro.2010.09.088. Epub 2010 Dec 18.</citation>
    <PMID>21168869</PMID>
  </reference>
  <reference>
    <citation>Hedegaard H, Warner M, Minino AM. Drug Overdose Deaths in the United States, 1999-2016. NCHS Data Brief. 2017 Dec;(294):1-8.</citation>
    <PMID>29319475</PMID>
  </reference>
  <reference>
    <citation>Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription opioid pain relievers---United States, 1999--2008. MMWR Morb Mortal Wkly Rep. 2011 Nov 4;60(43):1487-92.</citation>
    <PMID>22048730</PMID>
  </reference>
  <reference>
    <citation>Dunn LK, Durieux ME. Perioperative Use of Intravenous Lidocaine. Anesthesiology. 2017 Apr;126(4):729-737. doi: 10.1097/ALN.0000000000001527. No abstract available.</citation>
    <PMID>28114177</PMID>
  </reference>
  <reference>
    <citation>De Oliveira GS Jr, Fitzgerald P, Streicher LF, Marcus RJ, McCarthy RJ. Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery. Anesth Analg. 2012 Aug;115(2):262-7. doi: 10.1213/ANE.0b013e318257a380. Epub 2012 May 14.</citation>
    <PMID>22584558</PMID>
  </reference>
  <reference>
    <citation>Joshi GP, Jaschinski T, Bonnet F, Kehlet H; PROSPECT collaboration. Optimal pain management for radical prostatectomy surgery: what is the evidence? BMC Anesthesiol. 2015 Nov 4;15:159. doi: 10.1186/s12871-015-0137-2.</citation>
    <PMID>26530113</PMID>
  </reference>
  <reference>
    <citation>Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain. 2002 Jun;3(3):159-80. doi: 10.1054/jpai.2002.123652. No abstract available.</citation>
    <PMID>14622770</PMID>
  </reference>
  <reference>
    <citation>Marcus HJ, Hughes-Hallett A, Payne CJ, Cundy TP, Nandi D, Yang GZ, Darzi A. Trends in the diffusion of robotic surgery: A retrospective observational study. Int J Med Robot. 2017 Dec;13(4):e1870. doi: 10.1002/rcs.1870. Epub 2017 Nov 6.</citation>
    <PMID>29105982</PMID>
  </reference>
  <reference>
    <citation>Choi JE, You JH, Kim DK, Rha KH, Lee SH. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol. 2015 May;67(5):891-901. doi: 10.1016/j.eururo.2014.12.028. Epub 2015 Jan 6.</citation>
    <PMID>25572825</PMID>
  </reference>
  <reference>
    <citation>Avulova S, Smith JA Jr. Is Comparison of Robotic to Open Radical Prostatectomy Still Relevant? Eur Urol. 2018 May;73(5):672-673. doi: 10.1016/j.eururo.2018.01.011. Epub 2018 Feb 3. No abstract available.</citation>
    <PMID>29398264</PMID>
  </reference>
  <reference>
    <citation>D'Alonzo RC, Gan TJ, Moul JW, Albala DM, Polascik TJ, Robertson CN, Sun L, Dahm P, Habib AS. A retrospective comparison of anesthetic management of robot-assisted laparoscopic radical prostatectomy versus radical retropubic prostatectomy. J Clin Anesth. 2009 Aug;21(5):322-8. doi: 10.1016/j.jclinane.2008.09.005. Epub 2009 Aug 22.</citation>
    <PMID>19700296</PMID>
  </reference>
  <reference>
    <citation>Batley SE, Prasad V, Vasdev N, Mohan-S G. Post-Operative Pain Management in Patients Undergoing Robotic Urological Surgery. Curr Urol. 2016 Feb;9(1):5-11. doi: 10.1159/000442843. Epub 2016 Feb 10.</citation>
    <PMID>26989364</PMID>
  </reference>
  <reference>
    <citation>Woldu SL, Weinberg AC, Bergman A, Shapiro EY, Korets R, Motamedinia P, Badani KK. Pain and analgesic use after robot-assisted radical prostatectomy. J Endourol. 2014 May;28(5):544-8. doi: 10.1089/end.2013.0783. Epub 2014 Jan 30.</citation>
    <PMID>24400824</PMID>
  </reference>
  <reference>
    <citation>Jendoubi A, Naceur IB, Bouzouita A, Trifa M, Ghedira S, Chebil M, Houissa M. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: A prospective, double-blind, randomized, placebo-controlled study. Saudi J Anaesth. 2017 Apr-Jun;11(2):177-184. doi: 10.4103/1658-354X.203027.</citation>
    <PMID>28442956</PMID>
  </reference>
  <reference>
    <citation>Naik BI, Tsang S, Knisely A, Yerra S, Durieux ME. Retrospective case-control non-inferiority analysis of intravenous lidocaine in a colorectal surgery enhanced recovery program. BMC Anesthesiol. 2017 Jan 31;17(1):16. doi: 10.1186/s12871-017-0306-6.</citation>
    <PMID>28143397</PMID>
  </reference>
  <reference>
    <citation>Nakhli MS, Kahloul M, Guizani T, Zedini C, Chaouch A, Naija W. Intravenous lidocaine as adjuvant to general anesthesia in renal surgery. Libyan J Med. 2018 Dec;13(1):1433418. doi: 10.1080/19932820.2018.1433418.</citation>
    <PMID>29433385</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>Boris Mraovic</investigator_full_name>
    <investigator_title>Professor of Clinical Anesthesiology</investigator_title>
  </responsible_party>
  <keyword>prostatectomy</keyword>
  <keyword>partial nephrectomy</keyword>
  <keyword>robotic surgery</keyword>
  <keyword>intravenous lidocaine</keyword>
  <keyword>lidocaine hydrochloride</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lidocaine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 10, 2023</submitted>
    <returned>July 28, 2023</returned>
    <submitted>August 1, 2023</submitted>
    <returned>August 23, 2023</returned>
    <submitted>August 28, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03824808
org study id: 2012402
nct id: NCT03824808
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Controlling pain is fundamental during and after surgical procedures. This study examines
      pain associated with robotic assisted surgery on prostate cancer or a kidney mass. In recent
      years, the risk of opioids in the postoperative period has gained interest due to the growing
      epidemic of addiction, dependence, and overdose. In this study, the investigators expect a
      continuous infusion of intravenous lidocaine during the perioperative period to result in
      less pain and less opioid use.
In recent years, the risk of opioids in the post-operative period has gained interest due to
      the growing epidemic of addiction, dependence, and overdose. The rate of drug overdose
      secondary to opioids has continued to increase at an alarming rate. This has been a primary
      point of concern in all fields of medicine and Urology has not been an exception. This is
      also a nationwide government and public health concern. This has generated an increased focus
      on the use of non-opioid analgesics after surgery such as intravenous lidocaine.

      Opioids remain the primary source of relief for postoperative pain and have the potential to
      lead to significant morbidity. Opioids may delay recovery following surgery and have many
      well-known adverse effects including, but not limited to, nausea, vomiting and prolonged
      post-operative ileus. Furthermore, in one study, they inadequately provided pain control in
      50-60% of postoperative participants. This is a frequent report of participants because of
      the less than optimal utilization of the medications in fear of their dose dependent adverse
      effects and various contraindications. On the other hand, surplus medication following
      surgery is another prominent component of the opioid problem in Urologic practices. Bates et
      al. found that of the 586 participants that underwent a urological procedure that they
      reviewed, 67% of them had collected surplus medication. It is both necessary and beneficial
      for surgeons and participants to utilize dose-sparing strategies following surgery to
      decrease overall opioid usage and outpatient requirement.

      One mechanism that has already been employed for overall improvement in prostatectomies and
      partial nephrectomies is the use of the robotic assisted approach. Robot assisted partial
      nephrectomies (RALPN) and robotic assisted laparoscopic prostatectomies (RALP) are becoming a
      mainstay in urologic surgery and increasing annually. This coincides with a continuous
      downward trend of laparoscopic and open urologic procedures. RALPN has been shown in a
      meta-analysis to be more favorable than laparoscopic partial nephrectomies and will continue
      to be the surgical procedure of choice in the near future. RALP is also now the dominant
      surgical approach while open and laparoscopic prostatectomies becoming less frequent. Robotic
      assisted surgery is associated with improved functional outcomes, pain scores, shorter
      hospital stays, and increases in participants satisfaction in many studies.

      While there has been a pronounced increase in robotic surgery over the past 10 years that has
      demonstrated benefits for participants, there has been limited studies regarding the pain
      management for these participants. Robotic assisted surgery itself decreases pain levels
      compared to other approaches, but participants continue to experience mild to moderate pain
      levels in the postoperative period, which are classically managed with NSAIDs and opioids.

      Recently, Enhanced Recovery after Surgery protocols (ERAS) have been implemented in an
      attempt to decrease pain and opioid use as one outcome. ERAS utilizes multimodal analgesia
      and has shown improvement of participant satisfaction and perioperative opioid use. Systemic
      lidocaine is becoming more popular and regularly applied through this protocol and, other
      practices, in due to its analgesic, anti-hyperalgesia and anti-inflammatory properties that
      it contains. Systemic lidocaine mechanism of action is not fully understood, but it appears
      to be multifaceted. Systemic lidocaine inhibits voltage-gated sodium channels in both the
      peripheral and central nervous system. This is believed to cause an additive effect when
      combined with inhaled anesthetics which also work on the voltage-gated sodium channels in the
      central nervous system. Despite this summative effect, this is likely not the primary
      mechanism of action. Instead, it is believed to predominantly act on anti-inflammatory
      signaling and through inhibiting neuronal effects. Additionally, it reduces nociception and
      cardiovascular response to surgical stress and pain.

      This is a prospective, randomized, double-blinded, placebo-controlled clinical trial on
      lidocaine infusion for pain control and opioid consumption in participants undergoing either
      robotic-assisted laparoscopic prostatectomy or robotic-assisted laparoscopic partial
      nephrectomy at University of Missouri Hospital. Participants will be randomized in a 1:1
      fashion and stratified by the type of surgery to receive a perioperative intravenous 0.8%
      lidocaine infusion at 1 mg/kg/h if < age 65 and 0.5 mg/kg/h if ≥ age 65 or an equal volume
      and rate of normal saline as a placebo. The infusion will be started 15 minutes after
      endotracheal intubation and continue for 24 hours.

      The study that the investigators propose targets an area of urology that is underrepresented
      in the current literature despite its increasing importance. To the best of the
      investigator's knowledge, this has not been directly studied before, although it has been
      utilized numerous times in the ERAS protocol at the University of Missouri Hospital
      throughout the Division of Urology and Anesthesiology & Perioperative Medicine in
      participants undergoing robotic surgery. The benefits of intravenous lidocaine have been
      demonstrated in other areas and these results warrant a prospective, randomized,
      double-blinded, placebo controlled study to assess the lidocaine infusion effects for robot
      assisted laparoscopic prostatectomies and partial nephrectomies. As the number of robotic
      assisted surgeries and emphasis on opioid reduction continues, the evaluation of systemic
      lidocaine will be important in improving outcomes in urology.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will receive either intraoperative 0.8% lidocaine or normal saline at 1 mg/kg/h when younger than 65 years and 0.5 mg/kg/h when greater than or equal to the age of 65 to be delivered by continuous infusion for 24 hours.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The surgeon, anesthesiologist, operating room staff, participant, personnel in the postanesthesia care unit (PACU) as well as the investigators collecting the postoperative data will be blinded to the group allocation. Study medication is prepared and masked by an unblinded investigation drug pharmacist who is not involved in clinical care.
measure: Difference in post-operative pain scores measured by Visual Analog Scale
time frame: Through study completion, assessed up to 14 days (+/-) 7 days
description: 10-cm Visual Analog Scale (VAS), score of 0 "no pain" to a score of 10 "worst pain ever"
measure: Opioid consumption
time frame: Through study completion, assessed up to 14 days (+/-) 7 days
description: Difference in opioid consumption in first 24 hours, discharge and 14 days post-operatively (morphine equivalents)
measure: Length of hospital stay
time frame: At participant discharge, assessed up to 14 days (+/-) 7 days
description: Difference in length of hospital stay determined by surgeon excluding social factors that may delay discharge
measure: Duration of post-operative Ileus
time frame: During hospitalization, assessed up to 14 days (+/-) 7 days
description: Difference in post-operative Ileus duration
measure: Post-operative PACU time
time frame: During hospitalization, approximately 2 hours post-surgery
description: Difference in time in the Post Anesthesia Care Unit (PACU) after surgery
measure: Return of flatus
time frame: During hospitalization, assessed up to 14 days (+/-) 7 days
description: Difference in return of flatus after surgery
measure: Time to out of bed
time frame: During hospitalization, assessed up to 14 days (+/-) 7 days
description: Difference in time to out of bed to chair after surgery
measure: First ambulation in the hallway
time frame: During hospitalization, assessed up to 14 days (+/-) 7 days
description: Difference in time to first ambulation in the hallway after surgery
arm group label: Treatment group
arm group type: Active Comparator
description: Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution
arm group label: Control group
arm group type: Placebo Comparator
description: 0.9% Sodium Chloride Injection
intervention type: Drug
intervention name: Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution
description: Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection.
arm group label: Treatment group
other name: Lidocaine
intervention type: Drug
intervention name: 0.9% Sodium Chloride Injection
description: Sodium Chloride Injection USP is sterile, nonpyrogenic, isotonic and contains no bacteriostatic or antimicrobial agents.
arm group label: Control group
other name: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boris Mraovic, MD
role: Principal Investigator
affiliation: University of Missouri-Columbia
facility: 
country: United States
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PMID: 22048730
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PMID: 28114177
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PMID: 22584558
citation: Joshi GP, Jaschinski T, Bonnet F, Kehlet H; PROSPECT collaboration. Optimal pain management for radical prostatectomy surgery: what is the evidence? BMC Anesthesiol. 2015 Nov 4;15:159. doi: 10.1186/s12871-015-0137-2.
PMID: 26530113
citation: Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain. 2002 Jun;3(3):159-80. doi: 10.1054/jpai.2002.123652. No abstract available.
PMID: 14622770
citation: Marcus HJ, Hughes-Hallett A, Payne CJ, Cundy TP, Nandi D, Yang GZ, Darzi A. Trends in the diffusion of robotic surgery: A retrospective observational study. Int J Med Robot. 2017 Dec;13(4):e1870. doi: 10.1002/rcs.1870. Epub 2017 Nov 6.
PMID: 29105982
citation: Choi JE, You JH, Kim DK, Rha KH, Lee SH. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol. 2015 May;67(5):891-901. doi: 10.1016/j.eururo.2014.12.028. Epub 2015 Jan 6.
PMID: 25572825
citation: Avulova S, Smith JA Jr. Is Comparison of Robotic to Open Radical Prostatectomy Still Relevant? Eur Urol. 2018 May;73(5):672-673. doi: 10.1016/j.eururo.2018.01.011. Epub 2018 Feb 3. No abstract available.
PMID: 29398264
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PMID: 19700296
citation: Batley SE, Prasad V, Vasdev N, Mohan-S G. Post-Operative Pain Management in Patients Undergoing Robotic Urological Surgery. Curr Urol. 2016 Feb;9(1):5-11. doi: 10.1159/000442843. Epub 2016 Feb 10.
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citation: Woldu SL, Weinberg AC, Bergman A, Shapiro EY, Korets R, Motamedinia P, Badani KK. Pain and analgesic use after robot-assisted radical prostatectomy. J Endourol. 2014 May;28(5):544-8. doi: 10.1089/end.2013.0783. Epub 2014 Jan 30.
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PMID: 29433385
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: Boris Mraovic
investigator title: Professor of Clinical Anesthesiology
mesh term: Kidney Neoplasms
mesh term: Lidocaine
sharing ipd: No
submitted: July 10, 2023
returned: July 28, 2023
submitted: August 1, 2023
returned: August 23, 2023
submitted: August 28, 2023