<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/NCT03274453</url>
  </required_header>
  <id_info>
    <org_study_id>12-02202</org_study_id>
    <nct_id>NCT03274453</nct_id>
  </id_info>
  <brief_title>A Comparison of Ketamine Infusion Versus Placebo in Opioid Tolerant and Opioid Naive Patients After Spinal Fusion</brief_title>
  <official_title>A Prospective, Randomized, Double Blinded Comparison of Ketamine Infusion Versus Placebo in Opioid Tolerant and Opioid Naive Patients After Spinal Fusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU Langone Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <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>
      The aim of the proposed study is to examine the effectiveness of low dose postoperative&#xD;
      ketamine infusion as an analgesic adjuvant to morphine pca in opioid tolerant and opioid&#xD;
      naïve patients after major spine surgery. Primary endpoints of the study are to determine the&#xD;
      effectiveness of postoperative ketamine infusion in for the reduction of postoperative pain&#xD;
      and opioid requirements.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects aged 16 to 75, ASA I to III, scheduled for an elective lumbar fusion surgery of at&#xD;
      least two levels under general anaesthesia, were prospectively studied. We defined&#xD;
      opioid-tolerant as the daily use of opioid pain medication (oxycodone, morphine,&#xD;
      hydromorphone, fentanyl, methadone, or tramadol) during the two weeks before surgery.&#xD;
      Patients who did not fulfil that criterion were deemed to be opioid-naïve. Exclusion criteria&#xD;
      were poorly controlled hypertension, severe cardiac or pulmonary disease, elevated&#xD;
      intraocular pressure, severe hepatic or renal dysfunction, pregnancy, a history of&#xD;
      psychiatric disorder, inability to speak English, inability to understand the numerical pain&#xD;
      scale or to operate the patient-controlled analgesia pump, and known allergy to ketamine or&#xD;
      hydromorphone.&#xD;
&#xD;
      Patients were allocated to the opioid-naïve or opioid-tolerant arm as defined above, and&#xD;
      subsequently randomized into two groups, for a total of 4 groups: the opioid-naïve ketamine,&#xD;
      the opioid-naïve placebo, the opioid-tolerant ketamine, and the opioid-tolerant placebo.&#xD;
      Patients in each group were randomized to receive either a ketamine infusion (ketamine bolus&#xD;
      0.2 mg/kg over 30 minutes, started on arrival in post-anesthesia care unit (PACU), followed&#xD;
      by a fixed-rate infusion of 0.12 mg/kg/h for 24 hours), or placebo (identical volume/rate of&#xD;
      normal saline). Randomization within each group was performed by the study coordinator using&#xD;
      a computer-generated random number list in a 1:1 ratio. Study medication and placebo were&#xD;
      produced according to the randomization list in identical and consecutively numbered 250 mL&#xD;
      bags. The pharmacist was not involved in patient care. Information about treatment was&#xD;
      concealed but available for unblinding in case of acute complications. During the entire&#xD;
      study period investigators performing the postoperative assessments, medical staff (nurse,&#xD;
      anesthesiologist, and surgeon), and subjects were blinded to group allocation.&#xD;
&#xD;
      In all patients, general anesthesia was induced with propofol based on patient weight.&#xD;
      Rocuronium 0.6 - 1.2 mg/kg was used to facilitate endotracheal intubation. Anesthesia was&#xD;
      maintained with propofol (variable rate to maintain bispectral index (BIS) at a level&#xD;
      acceptable for surgical anesthesia), desflurane &lt;1.5% mixed of air and oxygen, fentanyl,&#xD;
      sufentanil, hydromorphone and morphine at the discretion of the anesthetic staff. Blood&#xD;
      pressure was maintained within 20% of baseline, and hypotension was treated at the discretion&#xD;
      of the anesthetic staff with isotonic sodium chloride solution, hetastarch, ephedrine and&#xD;
      phenylephrine intravenously.&#xD;
&#xD;
      Most patients received 1000 mg of IV acetaminophen at the end of surgery (see Table 2).&#xD;
      NSAIDs were not used in the immediate perioperative period because of the surgeons' concern&#xD;
      that they might impede bone healing and proper fusion.&#xD;
&#xD;
      For all patients, postoperative pain treatment during the first 24 hours consisted of&#xD;
      standard care of IV patient controlled analgesia (PCA) with hydromorphone (0.2 mg/dose,&#xD;
      lockout 6 min, maximum 2 mg/h), started on arrival in PACU. Preoperatively, the patients were&#xD;
      educated by the nursing staff in the use of the PCA pump and the numerical pain scale. Rescue&#xD;
      medication of IV hydromorphone 0.2 to 0.3 mg as needed was administered by a nurse with the&#xD;
      goal to reduce the numerical pain score (NPS; 0 = no pain, 10 = worst imaginable pain) below&#xD;
      4. Opioid pain medication was restricted to hydromorphone in order to allow for valid&#xD;
      comparison between the groups. After 24 hours, the PCA was discontinued and all patients were&#xD;
      treated according to the surgical department's standard regimen. Diazepam 2 mg IV was&#xD;
      administered for severe muscle spasms as needed.&#xD;
&#xD;
      Moderate to severe nausea or vomiting was treated with IV ondansetron 4 mg. If ondansetron&#xD;
      was ineffective, IV metoclopramide 10 mg was administered.&#xD;
&#xD;
      All postoperative assessments were performed by the study investigators or trained nurses&#xD;
      blinded to group allocation. Cumulative IV hydromorphone consumption was calculated from 0 to&#xD;
      24 hours postoperatively. NPS were recorded at arrival to PACU, then every 30 min during the&#xD;
      first 2 hours, and then every 2 hours on the floor during the first 24 hours after surgery&#xD;
      while patients were awake.&#xD;
&#xD;
      The primary outcome was cumulative hydromorphone consumption during the first 24h after&#xD;
      surgery. Secondary outcome was NPS in the same time period. We also recorded central nervous&#xD;
      system adverse events during the same period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2012</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 2014</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hydromorphone Use/24 Hours postOP in mg/kg</measure>
    <time_frame>24 Hours</time_frame>
    <description>Hydromorphone use during the first postoperative 24 hours in mg/kg</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">129</enrollment>
  <condition>Spinal Fusion</condition>
  <arm_group>
    <arm_group_label>Ketamine Naive</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Naive Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline will be administered at the same rate as the ketamine infusion. Infusion will be maintained for 24 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tolerant Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline will be administered at the same rate as the ketamine infusion. Infusion will be maintained for 24 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tolerant Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>0.12 mg/kg/hr of ketamine post surgery</description>
    <arm_group_label>Ketamine Naive</arm_group_label>
    <arm_group_label>Tolerant Ketamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Saline will be administered at the same rate as the ketamine infusion.</description>
    <arm_group_label>Naive Placebo</arm_group_label>
    <arm_group_label>Tolerant Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult and teenage (&gt;/=16) male or female who will undergo surgery for multilevel (&gt;4&#xD;
             level) spinal fusion from a posterior approach with general anesthesia, and who are&#xD;
             fluent English speakers such that they can complete the pain score and satisfaction&#xD;
             questionnaires whose scores are a critical outcome variable.&#xD;
&#xD;
          -  If female, subject is non-lactating and is either:&#xD;
&#xD;
          -  Not of childbearing potential&#xD;
&#xD;
          -  Of childbearing potential but is not pregnant at time of baseline as determined by&#xD;
             pre-surgical pregnancy testing.&#xD;
&#xD;
          -  Subject is ASA physical status 1, 2, or 3.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  anxiety&#xD;
&#xD;
          -  psychiatric disorder&#xD;
&#xD;
          -  Allergy or sensitivity to ketamine or dilaudid&#xD;
&#xD;
          -  Deemed un-acceptable by study team&#xD;
&#xD;
          -  Cognitively impaired (by history)&#xD;
&#xD;
          -  Subject requires chronic antipsychotic medication&#xD;
&#xD;
          -  Subject known to be in liver failure&#xD;
&#xD;
          -  Subject for whom opioids or ketamine are contraindicated&#xD;
&#xD;
          -  Patients with narrow angle glaucoma&#xD;
&#xD;
          -  Patients with a history of psychosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kirsten Boenigk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kirsten.Boenigk@nyumc.org</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York University School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <results_first_submitted>November 24, 2017</results_first_submitted>
  <results_first_submitted_qc>May 15, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2018</results_first_posted>
  <last_update_submitted>May 15, 2018</last_update_submitted>
  <last_update_submitted_qc>May 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Naive Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="P2">
          <title>Naive Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
        <group group_id="P3">
          <title>Tolerant Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="P4">
          <title>Tolerant Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="30"/>
                <participants group_id="P3" count="32"/>
                <participants group_id="P4" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="24"/>
                <participants group_id="P3" count="28"/>
                <participants group_id="P4" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Surgery Cancelled</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Naive Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="B2">
          <title>Naive Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
        <group group_id="B3">
          <title>Tolerant Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="B4">
          <title>Tolerant Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="34"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="28"/>
            <count group_id="B4" value="25"/>
            <count group_id="B5" value="111"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="28"/>
                    <measurement group_id="B4" value="25"/>
                    <measurement group_id="B5" value="111"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Sex</title>
              <category_list>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hydromorphone Use/24 Hours postOP in mg/kg</title>
        <description>Hydromorphone use during the first postoperative 24 hours in mg/kg</description>
        <time_frame>24 Hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naive Placebo</title>
            <description>Saline will be administered at the same rate as the ketamine infusion.</description>
          </group>
          <group group_id="O2">
            <title>Naive Ketamine</title>
            <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
          </group>
          <group group_id="O3">
            <title>Tolerant Placebo</title>
            <description>Saline will be administered at the same rate as the ketamine infusion.</description>
          </group>
          <group group_id="O4">
            <title>Tolerant Ketamine</title>
            <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Hydromorphone Use/24 Hours postOP in mg/kg</title>
          <description>Hydromorphone use during the first postoperative 24 hours in mg/kg</description>
          <units>mg/kg</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".13" lower_limit=".06" upper_limit=".18"/>
                    <measurement group_id="O2" value=".09" lower_limit=".05" upper_limit=".15"/>
                    <measurement group_id="O3" value=".27" lower_limit=".2" upper_limit=".37"/>
                    <measurement group_id="O4" value=".19" lower_limit=".16" upper_limit=".24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 hours</time_frame>
      <desc>Patients were systematically asked about side effects such as headaches, confusion, anxiety, excessive sedation and blurry vision when seen at 24 hours postoperatively. The records were also searched for evidence of such side effects.</desc>
      <group_list>
        <group group_id="E1">
          <title>Naive Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="E2">
          <title>Naive Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
        <group group_id="E3">
          <title>Tolerant Placebo</title>
          <description>Saline will be administered at the same rate as the ketamine infusion.</description>
        </group>
        <group group_id="E4">
          <title>Tolerant Ketamine</title>
          <description>After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.&#xD;
Infusion will be maintained for 24 hours.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Kirsten Boenigk</name_or_title>
      <organization>New York University School of Medicine</organization>
      <phone>212 598 6085</phone>
      <email>Kirsten.Boenigk@nyumc.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03274453
org study id: 12-02202
nct id: NCT03274453
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The aim of the proposed study is to examine the effectiveness of low dose postoperative
      ketamine infusion as an analgesic adjuvant to morphine pca in opioid tolerant and opioid
      naïve patients after major spine surgery. Primary endpoints of the study are to determine the
      effectiveness of postoperative ketamine infusion in for the reduction of postoperative pain
      and opioid requirements.
Subjects aged 16 to 75, ASA I to III, scheduled for an elective lumbar fusion surgery of at
      least two levels under general anaesthesia, were prospectively studied. We defined
      opioid-tolerant as the daily use of opioid pain medication (oxycodone, morphine,
      hydromorphone, fentanyl, methadone, or tramadol) during the two weeks before surgery.
      Patients who did not fulfil that criterion were deemed to be opioid-naïve. Exclusion criteria
      were poorly controlled hypertension, severe cardiac or pulmonary disease, elevated
      intraocular pressure, severe hepatic or renal dysfunction, pregnancy, a history of
      psychiatric disorder, inability to speak English, inability to understand the numerical pain
      scale or to operate the patient-controlled analgesia pump, and known allergy to ketamine or
      hydromorphone.

      Patients were allocated to the opioid-naïve or opioid-tolerant arm as defined above, and
      subsequently randomized into two groups, for a total of 4 groups: the opioid-naïve ketamine,
      the opioid-naïve placebo, the opioid-tolerant ketamine, and the opioid-tolerant placebo.
      Patients in each group were randomized to receive either a ketamine infusion (ketamine bolus
      0.2 mg/kg over 30 minutes, started on arrival in post-anesthesia care unit (PACU), followed
      by a fixed-rate infusion of 0.12 mg/kg/h for 24 hours), or placebo (identical volume/rate of
      normal saline). Randomization within each group was performed by the study coordinator using
      a computer-generated random number list in a 1:1 ratio. Study medication and placebo were
      produced according to the randomization list in identical and consecutively numbered 250 mL
      bags. The pharmacist was not involved in patient care. Information about treatment was
      concealed but available for unblinding in case of acute complications. During the entire
      study period investigators performing the postoperative assessments, medical staff (nurse,
      anesthesiologist, and surgeon), and subjects were blinded to group allocation.

      In all patients, general anesthesia was induced with propofol based on patient weight.
      Rocuronium 0.6 - 1.2 mg/kg was used to facilitate endotracheal intubation. Anesthesia was
      maintained with propofol (variable rate to maintain bispectral index (BIS) at a level
      acceptable for surgical anesthesia), desflurane <1.5% mixed of air and oxygen, fentanyl,
      sufentanil, hydromorphone and morphine at the discretion of the anesthetic staff. Blood
      pressure was maintained within 20% of baseline, and hypotension was treated at the discretion
      of the anesthetic staff with isotonic sodium chloride solution, hetastarch, ephedrine and
      phenylephrine intravenously.

      Most patients received 1000 mg of IV acetaminophen at the end of surgery (see Table 2).
      NSAIDs were not used in the immediate perioperative period because of the surgeons' concern
      that they might impede bone healing and proper fusion.

      For all patients, postoperative pain treatment during the first 24 hours consisted of
      standard care of IV patient controlled analgesia (PCA) with hydromorphone (0.2 mg/dose,
      lockout 6 min, maximum 2 mg/h), started on arrival in PACU. Preoperatively, the patients were
      educated by the nursing staff in the use of the PCA pump and the numerical pain scale. Rescue
      medication of IV hydromorphone 0.2 to 0.3 mg as needed was administered by a nurse with the
      goal to reduce the numerical pain score (NPS; 0 = no pain, 10 = worst imaginable pain) below
      4. Opioid pain medication was restricted to hydromorphone in order to allow for valid
      comparison between the groups. After 24 hours, the PCA was discontinued and all patients were
      treated according to the surgical department's standard regimen. Diazepam 2 mg IV was
      administered for severe muscle spasms as needed.

      Moderate to severe nausea or vomiting was treated with IV ondansetron 4 mg. If ondansetron
      was ineffective, IV metoclopramide 10 mg was administered.

      All postoperative assessments were performed by the study investigators or trained nurses
      blinded to group allocation. Cumulative IV hydromorphone consumption was calculated from 0 to
      24 hours postoperatively. NPS were recorded at arrival to PACU, then every 30 min during the
      first 2 hours, and then every 2 hours on the floor during the first 24 hours after surgery
      while patients were awake.

      The primary outcome was cumulative hydromorphone consumption during the first 24h after
      surgery. Secondary outcome was NPS in the same time period. We also recorded central nervous
      system adverse events during the same period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Hydromorphone Use/24 Hours postOP in mg/kg
time frame: 24 Hours
description: Hydromorphone use during the first postoperative 24 hours in mg/kg
arm group label: Ketamine Naive
arm group type: Active Comparator
description: After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.
Infusion will be maintained for 24 hours.
arm group label: Naive Placebo
arm group type: Placebo Comparator
description: Saline will be administered at the same rate as the ketamine infusion. Infusion will be maintained for 24 hours.
arm group label: Tolerant Placebo
arm group type: Placebo Comparator
description: Saline will be administered at the same rate as the ketamine infusion. Infusion will be maintained for 24 hours.
arm group label: Tolerant Ketamine
arm group type: Experimental
description: After an initial bolus of 0.2 mg/kg, the dose will be fixed at 0.12 mg/kg/hr of ketamine.
Infusion will be maintained for 24 hours.
intervention type: Drug
intervention name: Ketamine
description: 0.12 mg/kg/hr of ketamine post surgery
arm group label: Ketamine Naive
arm group label: Tolerant Ketamine
intervention type: Drug
intervention name: Saline
description: Saline will be administered at the same rate as the ketamine infusion.
arm group label: Naive Placebo
arm group label: Tolerant Placebo
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Kirsten Boenigk, MD
role: Principal Investigator
affiliation: Kirsten.Boenigk@nyumc.org
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ketamine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 