<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/NCT02252432</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00030109</org_study_id>
    <nct_id>NCT02252432</nct_id>
  </id_info>
  <brief_title>The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy</brief_title>
  <official_title>Intraoperative Ketamine and Methadone for Laminectomy: Effect on Recovery, Postoperative Pain, and Opioid Requirements</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cedars-Sinai Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to determine the pain-reducing effects of ketamine (Ketalar,&#xD;
      an FDA-approved drug for anesthesia) and methadone (Dolophine, a long-acting narcotic) after&#xD;
      lumbar laminectomy. The investigators would like to evaluate whether intraoperative use of&#xD;
      both drugs may be able to provide better control of pain after lumbar surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During and after the surgery, patients undergoing surgery most likely need narcotics&#xD;
      (opioids) that can cause side effects such as drowsiness and constipation. This can delay&#xD;
      your recovery. The investigator would like to determine if the intraoperative use of ketamine&#xD;
      and methadone will provide better pain control and reduce the use of narcotic painkiller&#xD;
      medications (analgesics) after lumbar surgery as compared to either drug (ketamine or&#xD;
      methadone) alone.&#xD;
&#xD;
      Ketamine is used to help to reduce the amount of the commonly used intravenous anesthetic&#xD;
      drugs, minimize heart rate and blood pressure instability during surgery, and to improve&#xD;
      outcomes after surgery (e.g. less pain, less constipation, less nausea and vomiting after&#xD;
      surgery, faster return of bowel function and shortened length of hospital stay).&#xD;
&#xD;
      Ketamine is approved by the U.S. Food and Drug Administration (FDA) to be used: as an&#xD;
      anesthetic and analgesic (painkiller). Ketamine is an &quot;adjuvant,&quot; which is a drug that may&#xD;
      increase the effectiveness or strength of other drugs when given at the same time. Ketamine&#xD;
      is administered as an adjuvant during anesthesia to produce anesthetic and analgesic-sparing&#xD;
      effects (reduce the amount of anesthetics and narcotics-painkiller drugs), hemodynamic&#xD;
      stability (to maintain the blood pressure and heart rate within normal rank) and side effect&#xD;
      reduction (e.g., constipation, nausea and vomiting, itching, and urinary retention). Ketamine&#xD;
      will be used as approved in this study. Ketamine is frequently used intraoperatively for pain&#xD;
      control in patients undergoing spine surgery at our institution and is within the standard of&#xD;
      care. The standard of care indicates that this is one possible method which has been&#xD;
      demonstrated to be safe and effective for patient care. This may vary at different&#xD;
      institutions.&#xD;
&#xD;
      Methadone is approved by the U.S. Food and Drug Administration (FDA) to be used: as an opioid&#xD;
      pain reliever, similar to morphine, and for narcotic detoxification to reduce withdrawal&#xD;
      symptoms. The dose of methadone that will be used in this study may be slightly higher than&#xD;
      the approved dose depending on the subject's weight. However, this dose of methadone is&#xD;
      frequently used intraoperatively for pain control in patients undergoing spine surgery at our&#xD;
      institution and is within the standard of care. This may vary at different institutions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No enough recruitments, very slow enrollment over the years&#xD;
  </why_stopped>
  <start_date type="Actual">February 2013</start_date>
  <completion_date type="Actual">January 2023</completion_date>
  <primary_completion_date type="Actual">January 2023</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>Opioid consumption obtained from the recorded data</measure>
    <time_frame>6 weeks</time_frame>
    <description>Perioperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts) Post discharge use of opioid consumption (data obtained from the follow up questionnaires approximately day 1-3 and 6 weeks after surgery).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative pain using a Verbal Rating Scale</measure>
    <time_frame>6 weeks</time_frame>
    <description>Postoperative measured at PACU, Day 1-3 and 6 weeks after surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nausea and vomiting will be measured with follow up</measure>
    <time_frame>6 weeks</time_frame>
    <description>Postoperative nausea and vomiting using a Verbal Rating Scale (0-10) at PACU, Day 1-3 and 6 weeks after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Constipation (Ileus) will be measured with follow up</measure>
    <time_frame>6 weeks</time_frame>
    <description>Day 1-3 and 6 weeks after surgery</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Laminectomy</condition>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min))</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Will receive a single dose of IV methadone (0.2 mg/kg) preinduction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine + methadone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)</description>
    <arm_group_label>Ketamine + methadone</arm_group_label>
    <arm_group_label>Methadone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>A single dose of IV methadone (0.2 mg/kg) preinduction.</description>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_label>Ketamine + methadone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine + methadone</intervention_name>
    <description>Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)</description>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_label>Methadone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • 18 - 80 years old of either gender, scheduled for elective lumbar laminectomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) IV and above&#xD;
&#xD;
          -  Intolerance, allergy, or contraindication to use of any medications used in this study&#xD;
&#xD;
          -  Significant coronary artery disease (abnormal stress test, myocardial infarction&#xD;
&#xD;
               -  within the last 3 months)&#xD;
&#xD;
          -  Increased intraocular pressure (e.g., untreated glaucoma)&#xD;
&#xD;
          -  Uncontrolled hypertension (BP &gt; 140/90)&#xD;
&#xD;
          -  Sleep apnea and currently on continuous positive airway pressure (CPAP)&#xD;
&#xD;
          -  Increased intracranial pressure or clinical signs thereof&#xD;
&#xD;
          -  History of intracranial surgery, stroke, or brain aneurysm&#xD;
&#xD;
          -  Cardiac arrhythmias particularly prolonged QT syndrome&#xD;
&#xD;
          -  Drugs known to cause prolonged qT: class (IA) antiarrhythmics (quinidine,&#xD;
             procainamide, disopyramide), class III antiarrhythmics (sotalol, dofetilide,&#xD;
             ibutilide, amiodarone), haloperidol, thioridazine, arsenic trioxide, HIV protease&#xD;
             inhibitors, tricyclic antidepressants&#xD;
&#xD;
          -  Individuals with significant psychological disorders including: schizophrenia, mania,&#xD;
             bipolar disorder or psychosis&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Emergent laminectomy&#xD;
&#xD;
          -  Those already receiving ketamine or methadone prior to surgery&#xD;
&#xD;
          -  Morbid obesity (BMI &gt; 40 kg/m2) AND/OR weight &gt; 150 kg&#xD;
&#xD;
          -  Chronic renal failure ( creatinine &gt; 2.0 mg/dL)&#xD;
&#xD;
          -  Liver failure e.g., active cirrhosis&#xD;
&#xD;
          -  Alcohol or substance abuse within in the past 3 months&#xD;
&#xD;
          -  Uncorrected hypokalemia, hypomagnesemia, hypocalcemia (can be due to diuretics,&#xD;
             mineralocorticoid use, laxatives)&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease (COPD)/Hypercarbia&#xD;
&#xD;
          -  Restrictive lung disease (pulmonary fibrosis, myasthenia gravis)&#xD;
&#xD;
          -  Congestive heart failure&#xD;
&#xD;
          -  Thyroid disease&#xD;
&#xD;
          -  Organ transplant patients&#xD;
&#xD;
          -  Drugs/substances known to inhibit methadone metabolism: macrolide antibiotics e.g.,&#xD;
             erythromycin, cimetidine, astemizole, voriconazole, grapefruit juice&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roya Yumul, M.D., PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cedars-Sinai Medical Center</investigator_affiliation>
    <investigator_full_name>Roya Yumul, M.D.,PhD.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>KETAMINE</keyword>
  <keyword>METHADONE</keyword>
  <keyword>POSTOPERATIVE PAIN</keyword>
  <keyword>OPIOID REQUIREMENTS</keyword>
  <keyword>Length of hospital stay</keyword>
  <keyword>Perioperative outcomes</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>Ketamine</mesh_term>
    <mesh_term>Methadone</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/NCT02252432
org study id: Pro00030109
nct id: NCT02252432
lead sponsor: 
has dmc: No
The purpose of this research is to determine the pain-reducing effects of ketamine (Ketalar,
      an FDA-approved drug for anesthesia) and methadone (Dolophine, a long-acting narcotic) after
      lumbar laminectomy. The investigators would like to evaluate whether intraoperative use of
      both drugs may be able to provide better control of pain after lumbar surgery.
During and after the surgery, patients undergoing surgery most likely need narcotics
      (opioids) that can cause side effects such as drowsiness and constipation. This can delay
      your recovery. The investigator would like to determine if the intraoperative use of ketamine
      and methadone will provide better pain control and reduce the use of narcotic painkiller
      medications (analgesics) after lumbar surgery as compared to either drug (ketamine or
      methadone) alone.

      Ketamine is used to help to reduce the amount of the commonly used intravenous anesthetic
      drugs, minimize heart rate and blood pressure instability during surgery, and to improve
      outcomes after surgery (e.g. less pain, less constipation, less nausea and vomiting after
      surgery, faster return of bowel function and shortened length of hospital stay).

      Ketamine is approved by the U.S. Food and Drug Administration (FDA) to be used: as an
      anesthetic and analgesic (painkiller). Ketamine is an "adjuvant," which is a drug that may
      increase the effectiveness or strength of other drugs when given at the same time. Ketamine
      is administered as an adjuvant during anesthesia to produce anesthetic and analgesic-sparing
      effects (reduce the amount of anesthetics and narcotics-painkiller drugs), hemodynamic
      stability (to maintain the blood pressure and heart rate within normal rank) and side effect
      reduction (e.g., constipation, nausea and vomiting, itching, and urinary retention). Ketamine
      will be used as approved in this study. Ketamine is frequently used intraoperatively for pain
      control in patients undergoing spine surgery at our institution and is within the standard of
      care. The standard of care indicates that this is one possible method which has been
      demonstrated to be safe and effective for patient care. This may vary at different
      institutions.

      Methadone is approved by the U.S. Food and Drug Administration (FDA) to be used: as an opioid
      pain reliever, similar to morphine, and for narcotic detoxification to reduce withdrawal
      symptoms. The dose of methadone that will be used in this study may be slightly higher than
      the approved dose depending on the subject's weight. However, this dose of methadone is
      frequently used intraoperatively for pain control in patients undergoing spine surgery at our
      institution and is within the standard of care. This may vary at different institutions.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Opioid consumption obtained from the recorded data
time frame: 6 weeks
description: Perioperative use of opioid consumption inside hospital (recorded by study staff and data obtained from patient charts) Post discharge use of opioid consumption (data obtained from the follow up questionnaires approximately day 1-3 and 6 weeks after surgery).
measure: Postoperative pain using a Verbal Rating Scale
time frame: 6 weeks
description: Postoperative measured at PACU, Day 1-3 and 6 weeks after surgery
measure: Nausea and vomiting will be measured with follow up
time frame: 6 weeks
description: Postoperative nausea and vomiting using a Verbal Rating Scale (0-10) at PACU, Day 1-3 and 6 weeks after surgery
measure: Constipation (Ileus) will be measured with follow up
time frame: 6 weeks
description: Day 1-3 and 6 weeks after surgery
arm group label: Ketamine
arm group type: Active Comparator
description: A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min))
arm group label: Methadone
arm group type: Active Comparator
description: Will receive a single dose of IV methadone (0.2 mg/kg) preinduction
arm group label: Ketamine + methadone
arm group type: Experimental
description: Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)
intervention type: Drug
intervention name: Ketamine
description: A bolus of intravenous (IV) ketamine during induction (0.5mg/kg), and an IV infusion of ketamine intraoperatively (5 mcg/kg/min)
arm group label: Ketamine + methadone
arm group label: Methadone
intervention type: Drug
intervention name: Methadone
description: A single dose of IV methadone (0.2 mg/kg) preinduction.
arm group label: Ketamine
arm group label: Ketamine + methadone
intervention type: Drug
intervention name: Ketamine + methadone
description: Methadone (0.2 mg/kg) preinduction, a bolus of IV ketamine (0.5 mg/kg) during induction and IV ketamine infusion intraoperatively (5 mcg/kg/min)
arm group label: Ketamine
arm group label: Methadone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Roya Yumul, M.D., PhD.
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Cedars-Sinai Medical Center
investigator full name: Roya Yumul, M.D.,PhD.
investigator title: Principal Investigator
mesh term: Pain, Postoperative
mesh term: Ketamine
mesh term: Methadone