<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/NCT03031340</url>
  </required_header>
  <id_info>
    <org_study_id>11-01-004</org_study_id>
    <nct_id>NCT03031340</nct_id>
  </id_info>
  <brief_title>Evaluating the Role of Pregabalin in Reducing Opioid Requirement in Spinal Fusion Surgeries of Two or More Vertebrae</brief_title>
  <official_title>Double Blinded, Randomized, Placebo Controlled Study in Evaluating the Role of Pregabalin in Reducing Opioid Requirement in Spinal Fusion Surgeries of Two or More Vertebrae</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Montefiore Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Montefiore Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To see if the administration of 3 dosses of pregabalin (1 dose preoperative, 2 doses&#xD;
      postoperative) will reduce the postoperative opiate requirements of patients undergoing&#xD;
      spinal fusion surgeries of two or more vertebrae.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction&#xD;
&#xD;
      Postoperative pain is often thought to be inadequately treated in half of all surgical&#xD;
      procedures . Postoperative pain management in patients undergoing spine surgery is often&#xD;
      difficult and challenging. The challenges of opioid tolerance and paucity of efficient opioid&#xD;
      sparing agents makes pain management even more complex. Preoperative strategies that can&#xD;
      minimize postoperative pain include proper surgical technique, which would avoid or lessen&#xD;
      nerve injury, and the use of preemptive analgesia. Studies have shown that the intensity of&#xD;
      acute postoperative pain correlates with the risk of developing persistent pain. Post&#xD;
      operative pain results from the direct activation of nociceptors, inflammation, and in some&#xD;
      cases direct nerve injury to the nerves.&#xD;
&#xD;
      The data on preemptive analgesia are inconclusive . The concept, however, has sparked&#xD;
      interest in mechanism-based analgesia and highlighted the process of central sensitization as&#xD;
      a target for analgesic intervention .&#xD;
&#xD;
      The use of opioids is limited by their side effect profile and by the poor response of&#xD;
      certain types of pain . The multiplicity of mechanisms involved in pain suggests that&#xD;
      combination of opioid and non-opioid analgesic drugs will enhance analgesia. The concomitant&#xD;
      reduction in opioid requirements, anticipated with the use of multimodal therapy, can also be&#xD;
      expected to reduce side effects.&#xD;
&#xD;
      Pregabalin is a lipophilic gamma-amino-butyric acid (GABA) analog with anticonvulsant,&#xD;
      anxiolytic and sleep-modulating properties. The effectiveness of pregabalin has been&#xD;
      demonstrated in several pain models including neuropathic pain , , incisional injury and&#xD;
      inflammation . Several previous studies conducted found that the use of gabapentin, the&#xD;
      predecessor of pregabalin, reduced post operative pain and opioid requirements and decreased&#xD;
      the number of opioid related adverse events , . Pregabalin is the pharmacologically active S&#xD;
      enantiomer of 3-aminomethyl-5-methyl hexanoic acid; it has a similar pharmacological profile&#xD;
      to gabapentin . Like gabapentin, pregabalin also binds to the α-2-δ subunit of voltage gated&#xD;
      calcium channels, reducing the release of excitatory neurotransmitters: glutamate,&#xD;
      norepinephrine, serotonin, dopamine and substance-P. It blocks the development of&#xD;
      hyperalgesia and inhibits central sensitization , . Pregabalin has greater absorption,&#xD;
      bioavailability, anticonvulsant, anti-hyperalgesic and anxiolytic properties than gabapentin&#xD;
      , .&#xD;
&#xD;
      Rationale for selecting spine surgeries. Low back pain is a major medical problem and a&#xD;
      significant source of disability for people under 45 years of age . Spine surgeries are&#xD;
      considered to be among the most complex, and long-lasting. The postoperative period is&#xD;
      particularly challenging for efficient pain management. Postoperative pain may be due to&#xD;
      nociceptive pain as well as hyperalgesia secondary to surgical trauma. Central sensitization&#xD;
      is a key mechanism in the development and maintenance of chronic pain, particularly for&#xD;
      neuropathic pain and pain after spine surgery .&#xD;
&#xD;
      Rationale for using pregabalin&#xD;
&#xD;
      Animal studies in surgical pain models and clinical studies of inflammatory pain in&#xD;
      volunteers demonstrated that both of these interventions can cause allodynia and&#xD;
      hyperalgesia- these are both susceptible to pregabalin and its analogues , .&#xD;
&#xD;
      The sensitization of dorsal horn neurons has been demonstrated in acute pain models and may&#xD;
      be responsible for the development of chronic pain after surgery , , . The ability of&#xD;
      pregabalin to reduce the hyperexcitability of dorsal neurons induced by tissue damage&#xD;
      confirms its role in preemptive analgesia . Its anxiolytic effect and ability to prevent&#xD;
      opioid tolerance could also be beneficial . Alternately, antihyperalgesia drugs like&#xD;
      pregabalin may block pathological pain, while leaving the physiological pain (with its&#xD;
      protective function) intact. This class of agents function through opiate independent&#xD;
      pathways and do not affect gut motility .&#xD;
&#xD;
      Pharmacodynamics and Pharmacokinetics:&#xD;
&#xD;
      Pregabalin is an FDA-approved drug available in 50-300 mg/day (the FDA-recommended maximum is&#xD;
      300mg/day). It is rapidly absorbed following oral administration with peak plasma&#xD;
      concentration occurring between 0.7-1.3hrs. The mean oral bioavailability is 90% after&#xD;
      1-300mg of single oral dose. The elimination half-life is 5.5-6.5 hrs independent of dose and&#xD;
      repeated administration. Plasma clearance is essentially equivalent to renal clearance. The&#xD;
      elimination rate is nearly proportional to creatinine clearance and dose reduction is&#xD;
      recommended in patients with low creatinine clearance. Ninety percent of the dose is excreted&#xD;
      in the urine .&#xD;
&#xD;
      Adverse events of pregabalin Pregabalin is generally well tolerated and associated with mild&#xD;
      to moderate adverse events which are dose dependent. The most frequently reported (22-29%)&#xD;
      are dizziness and somnolence. Other less common adverse events reported are dry mouth,&#xD;
      peripheral edema, blurred vision and inability to concentrate .&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Our hypothesis is that pre-operative administration of pregabalin can reduce the central&#xD;
      neural sensitization, efficiently reverse inflammatory hyperalgesia and can cause opioid&#xD;
      sparing effect. These actions of pregabalin will reduce the amount of opioids need by the&#xD;
      patient intraoperatively and in the immediate postoperative period. The reduction of opioids&#xD;
      will lessen opioid related adverse events and will augment the perioperative satisfaction&#xD;
      level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Incidence of AE&#xD;
  </why_stopped>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>Phase 3</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>Postoperative Opioid Requirement</measure>
    <time_frame>48 hours</time_frame>
    <description>The primary objective of this study is to evaluate the role of three doses of pregabalin on intra and postoperative (48hrs) opioid requirements in patients undergoing fusion of two or more vertebrae.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Using the Visual Analog Scale (VAS) Pain Score</measure>
    <time_frame>2 hours, 24 hours, 48 hours</time_frame>
    <description>evaluate pain using the visual analog scale (VAS) pain score at two hrs post-op, the morning following surgery 24 hours and 48 hours post-op</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of 48 Hours Post Operative Nausea and Vomiting</measure>
    <time_frame>48 hours</time_frame>
    <description>Find the incidence of 48 hours post operative nausea and vomiting in the target population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post Operative Cognitive Function</measure>
    <time_frame>48 hours</time_frame>
    <description>48 hours post operative headache, dizziness, sedation and blurred vision</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-operative Anxiety</measure>
    <time_frame>24 hours prior to surgery</time_frame>
    <description>Measure the level of pre-operative anxiety using the visual analog scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anesthesia Satisfaction</measure>
    <time_frame>24 hours post surgery</time_frame>
    <description>To measure the level of overall anesthesia satisfaction among the two groups at discharge.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Spinal Fusion</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregabalin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregabalin</intervention_name>
    <description>On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
    <arm_group_label>Pregabalin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age : &gt; 18 years old&#xD;
&#xD;
          -  Fusion of &gt; two vertebrae&#xD;
&#xD;
          -  Capacity to provide consent&#xD;
&#xD;
          -  ASA I-IV&#xD;
&#xD;
          -  Ability to swallow capsules&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Plan of care includes intubated ICU admission post-op&#xD;
&#xD;
          -  Allergy to gabapentin or pregabalin&#xD;
&#xD;
          -  Two week prior use of pregabalin&#xD;
&#xD;
          -  Significant renal dysfunction (creatinine level &gt;2)&#xD;
&#xD;
          -  Severe cardiovascular disease&#xD;
&#xD;
          -  History of frequent headaches or dizziness&#xD;
&#xD;
          -  Significant hepatic dysfunction (LFT's &gt; 4 times the normal ranges)&#xD;
&#xD;
          -  Active usage of alcohol or illicit substances three days prior to surgery&#xD;
&#xD;
          -  History of seizure disorders&#xD;
&#xD;
          -  Taking medication for anxiety, antiseizure, and psychiatric diagnoses&#xD;
&#xD;
          -  Re-operation patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 22, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <results_first_submitted>September 13, 2018</results_first_submitted>
  <results_first_submitted_qc>September 13, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 10, 2018</results_first_posted>
  <last_update_submitted>August 12, 2019</last_update_submitted>
  <last_update_submitted_qc>August 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Montefiore Medical Center</investigator_affiliation>
    <investigator_full_name>Singh Nair</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Spinal fusion</keyword>
  <keyword>pregabalin</keyword>
  <keyword>Spinal fusion surgeries</keyword>
  <keyword>two or more vertebrae</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pregabalin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>placebo: placebo</description>
        </group>
        <group group_id="P2">
          <title>Pregabalin</title>
          <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>placebo: placebo</description>
        </group>
        <group group_id="B2">
          <title>Pregabalin</title>
          <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
        </group>
        <group group_id="B3">
          <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="2"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="3"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Opioid Requirement</title>
        <description>The primary objective of this study is to evaluate the role of three doses of pregabalin on intra and postoperative (48hrs) opioid requirements in patients undergoing fusion of two or more vertebrae.</description>
        <time_frame>48 hours</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Opioid Requirement</title>
          <description>The primary objective of this study is to evaluate the role of three doses of pregabalin on intra and postoperative (48hrs) opioid requirements in patients undergoing fusion of two or more vertebrae.</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Using the Visual Analog Scale (VAS) Pain Score</title>
        <description>evaluate pain using the visual analog scale (VAS) pain score at two hrs post-op, the morning following surgery 24 hours and 48 hours post-op</description>
        <time_frame>2 hours, 24 hours, 48 hours</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Using the Visual Analog Scale (VAS) Pain Score</title>
          <description>evaluate pain using the visual analog scale (VAS) pain score at two hrs post-op, the morning following surgery 24 hours and 48 hours post-op</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of 48 Hours Post Operative Nausea and Vomiting</title>
        <description>Find the incidence of 48 hours post operative nausea and vomiting in the target population</description>
        <time_frame>48 hours</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of 48 Hours Post Operative Nausea and Vomiting</title>
          <description>Find the incidence of 48 hours post operative nausea and vomiting in the target population</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post Operative Cognitive Function</title>
        <description>48 hours post operative headache, dizziness, sedation and blurred vision</description>
        <time_frame>48 hours</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Post Operative Cognitive Function</title>
          <description>48 hours post operative headache, dizziness, sedation and blurred vision</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pre-operative Anxiety</title>
        <description>Measure the level of pre-operative anxiety using the visual analog scale (VAS)</description>
        <time_frame>24 hours prior to surgery</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Pre-operative Anxiety</title>
          <description>Measure the level of pre-operative anxiety using the visual analog scale (VAS)</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anesthesia Satisfaction</title>
        <description>To measure the level of overall anesthesia satisfaction among the two groups at discharge.</description>
        <time_frame>24 hours post surgery</time_frame>
        <population>Data not collected therefore no analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>placebo: placebo</description>
          </group>
          <group group_id="O2">
            <title>Pregabalin</title>
            <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Anesthesia Satisfaction</title>
          <description>To measure the level of overall anesthesia satisfaction among the two groups at discharge.</description>
          <population>Data not collected therefore no analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>placebo: placebo</description>
        </group>
        <group group_id="E2">
          <title>Pregabalin</title>
          <description>Pregabalin: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <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="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
              </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>Dr.Singh Nair</name_or_title>
      <organization>Montefiore Medical Center</organization>
      <phone>7189205932</phone>
      <email>sinair@montefiore.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/NCT03031340
org study id: 11-01-004
nct id: NCT03031340
lead sponsor: 
has dmc: Yes
To see if the administration of 3 dosses of pregabalin (1 dose preoperative, 2 doses
      postoperative) will reduce the postoperative opiate requirements of patients undergoing
      spinal fusion surgeries of two or more vertebrae.
Introduction

      Postoperative pain is often thought to be inadequately treated in half of all surgical
      procedures . Postoperative pain management in patients undergoing spine surgery is often
      difficult and challenging. The challenges of opioid tolerance and paucity of efficient opioid
      sparing agents makes pain management even more complex. Preoperative strategies that can
      minimize postoperative pain include proper surgical technique, which would avoid or lessen
      nerve injury, and the use of preemptive analgesia. Studies have shown that the intensity of
      acute postoperative pain correlates with the risk of developing persistent pain. Post
      operative pain results from the direct activation of nociceptors, inflammation, and in some
      cases direct nerve injury to the nerves.

      The data on preemptive analgesia are inconclusive . The concept, however, has sparked
      interest in mechanism-based analgesia and highlighted the process of central sensitization as
      a target for analgesic intervention .

      The use of opioids is limited by their side effect profile and by the poor response of
      certain types of pain . The multiplicity of mechanisms involved in pain suggests that
      combination of opioid and non-opioid analgesic drugs will enhance analgesia. The concomitant
      reduction in opioid requirements, anticipated with the use of multimodal therapy, can also be
      expected to reduce side effects.

      Pregabalin is a lipophilic gamma-amino-butyric acid (GABA) analog with anticonvulsant,
      anxiolytic and sleep-modulating properties. The effectiveness of pregabalin has been
      demonstrated in several pain models including neuropathic pain , , incisional injury and
      inflammation . Several previous studies conducted found that the use of gabapentin, the
      predecessor of pregabalin, reduced post operative pain and opioid requirements and decreased
      the number of opioid related adverse events , . Pregabalin is the pharmacologically active S
      enantiomer of 3-aminomethyl-5-methyl hexanoic acid; it has a similar pharmacological profile
      to gabapentin . Like gabapentin, pregabalin also binds to the α-2-δ subunit of voltage gated
      calcium channels, reducing the release of excitatory neurotransmitters: glutamate,
      norepinephrine, serotonin, dopamine and substance-P. It blocks the development of
      hyperalgesia and inhibits central sensitization , . Pregabalin has greater absorption,
      bioavailability, anticonvulsant, anti-hyperalgesic and anxiolytic properties than gabapentin
      , .

      Rationale for selecting spine surgeries. Low back pain is a major medical problem and a
      significant source of disability for people under 45 years of age . Spine surgeries are
      considered to be among the most complex, and long-lasting. The postoperative period is
      particularly challenging for efficient pain management. Postoperative pain may be due to
      nociceptive pain as well as hyperalgesia secondary to surgical trauma. Central sensitization
      is a key mechanism in the development and maintenance of chronic pain, particularly for
      neuropathic pain and pain after spine surgery .

      Rationale for using pregabalin

      Animal studies in surgical pain models and clinical studies of inflammatory pain in
      volunteers demonstrated that both of these interventions can cause allodynia and
      hyperalgesia- these are both susceptible to pregabalin and its analogues , .

      The sensitization of dorsal horn neurons has been demonstrated in acute pain models and may
      be responsible for the development of chronic pain after surgery , , . The ability of
      pregabalin to reduce the hyperexcitability of dorsal neurons induced by tissue damage
      confirms its role in preemptive analgesia . Its anxiolytic effect and ability to prevent
      opioid tolerance could also be beneficial . Alternately, antihyperalgesia drugs like
      pregabalin may block pathological pain, while leaving the physiological pain (with its
      protective function) intact. This class of agents function through opiate independent
      pathways and do not affect gut motility .

      Pharmacodynamics and Pharmacokinetics:

      Pregabalin is an FDA-approved drug available in 50-300 mg/day (the FDA-recommended maximum is
      300mg/day). It is rapidly absorbed following oral administration with peak plasma
      concentration occurring between 0.7-1.3hrs. The mean oral bioavailability is 90% after
      1-300mg of single oral dose. The elimination half-life is 5.5-6.5 hrs independent of dose and
      repeated administration. Plasma clearance is essentially equivalent to renal clearance. The
      elimination rate is nearly proportional to creatinine clearance and dose reduction is
      recommended in patients with low creatinine clearance. Ninety percent of the dose is excreted
      in the urine .

      Adverse events of pregabalin Pregabalin is generally well tolerated and associated with mild
      to moderate adverse events which are dose dependent. The most frequently reported (22-29%)
      are dizziness and somnolence. Other less common adverse events reported are dry mouth,
      peripheral edema, blurred vision and inability to concentrate .

      Hypothesis:

      Our hypothesis is that pre-operative administration of pregabalin can reduce the central
      neural sensitization, efficiently reverse inflammatory hyperalgesia and can cause opioid
      sparing effect. These actions of pregabalin will reduce the amount of opioids need by the
      patient intraoperatively and in the immediate postoperative period. The reduction of opioids
      will lessen opioid related adverse events and will augment the perioperative satisfaction
      level.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Postoperative Opioid Requirement
time frame: 48 hours
description: The primary objective of this study is to evaluate the role of three doses of pregabalin on intra and postoperative (48hrs) opioid requirements in patients undergoing fusion of two or more vertebrae.
measure: Pain Using the Visual Analog Scale (VAS) Pain Score
time frame: 2 hours, 24 hours, 48 hours
description: evaluate pain using the visual analog scale (VAS) pain score at two hrs post-op, the morning following surgery 24 hours and 48 hours post-op
measure: Incidence of 48 Hours Post Operative Nausea and Vomiting
time frame: 48 hours
description: Find the incidence of 48 hours post operative nausea and vomiting in the target population
measure: Post Operative Cognitive Function
time frame: 48 hours
description: 48 hours post operative headache, dizziness, sedation and blurred vision
measure: Pre-operative Anxiety
time frame: 24 hours prior to surgery
description: Measure the level of pre-operative anxiety using the visual analog scale (VAS)
measure: Anesthesia Satisfaction
time frame: 24 hours post surgery
description: To measure the level of overall anesthesia satisfaction among the two groups at discharge.
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: Pregabalin
arm group type: Experimental
intervention type: Drug
intervention name: Pregabalin
description: On the day of the surgery, 1hour + 15 minutes before the surgery starts, the subject will receive either 300mg of pregabalin or a similarly packaged placebo. On post operative day one, 150 mg of pregabalin or placebo will be given in two doses 12hrs apart.
arm group label: Pregabalin
intervention type: Other
intervention name: placebo
description: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Montefiore Medical Center
investigator full name: Singh Nair
investigator title: Assistant Professor
mesh term: Pregabalin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 