<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/NCT02190903</url>
  </required_header>
  <id_info>
    <org_study_id>818017</org_study_id>
    <nct_id>NCT02190903</nct_id>
  </id_info>
  <brief_title>A Trial To Assess Risk of Delirium in Older Adults Undergoing Hip Fracture Surgery With Spinal or General Anesthesia</brief_title>
  <official_title>A Randomized Controlled Trial To Assess Risk of Delirium in Older Adults Undergoing Hip Fracture Surgery With Spinal or General Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot project will address the gaps in knowledge regarding the effect of anesthetic&#xD;
      technique on the risk of delirium through an adequately-powered trial employing standardized&#xD;
      regimens for treatment and outcome assessment to test the hypothesis that use of spinal&#xD;
      versus general anesthesia decreases the risk of delirium after hip fracture surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives Overall objectives Overall Objectives Specific Aims&#xD;
&#xD;
        1. To compare the effect of spinal versus general anesthesia on rates of postoperative&#xD;
           delirium after hip fracture surgery. We hypothesize that rates of delirium after hip&#xD;
           fracture surgery will be lower among patients receiving spinal versus general&#xD;
           anesthesia.&#xD;
&#xD;
        2. To develop, field-test, and conduct a qualitative evaluation of protocols and procedures&#xD;
           for a planned multicenter trial to test the association of anesthesia technique with&#xD;
           survival and recovery of function in activities of daily living ambulatory ability at&#xD;
           six months after hip fracture.&#xD;
&#xD;
      Primary outcome variable(s) The primary outcome variable is the rate of delirium after hip&#xD;
      fracture surgery.&#xD;
&#xD;
      Background Delirium, or a disturbance of consciousness and a change in cognition that develop&#xD;
      over a short period of time, (1) complicates 2.6 million hospitalizations among U.S. adults&#xD;
      aged 65 or older each year. (2,3) Patients who experience delirium during hospitalization&#xD;
      face increased risks morbidity, mortality, and functional disability. (4) Each year, delirium&#xD;
      accounts for $6.9 billion in Medicare hospital expenditures. (5) Delirium occurs in 35% to&#xD;
      65% of the 320,000 older U.S. adults hospitalized for hip fracture each year. (6) While&#xD;
      adverse survival and functional outcomes are common after hip fracture, (7) a single episode&#xD;
      of delirium doubles the odds of both new functional dependence and new ambulatory disability&#xD;
      at six months after fracture, and triples the odds of death or new nursing home placement.&#xD;
      (8) Compared to general endotracheal anesthesia, spinal anesthesia may decrease the incidence&#xD;
      of postoperative delirium after hip fracture surgery. Small randomized trials of anesthesia&#xD;
      type for hip fracture have suggested a 50% lower risk of acute confusion after hip fracture&#xD;
      surgery with spinal anesthesia, (9) but the heterogeneity of outcome definitions and&#xD;
      measurement strategies employed by past trials, along with their use of historical anesthesia&#xD;
      practices limit their applicability to current practice.&#xD;
&#xD;
      As a result of these limitations, clinical equipoise continues to exist regarding the optimal&#xD;
      anesthetic technique for hip fracture care. Compared to general anesthesia, spinal anesthesia&#xD;
      may offer potential benefits not limited to decreased delirium. These may include decreased&#xD;
      intraoperative blood loss, and decreased risks of postoperative thromboembolic events,&#xD;
      respiratory infections and malignant hyperthermia. At the same time, spinal anesthesia may be&#xD;
      associated with greater hypotension than general anesthesia, and may carry small risks of&#xD;
      bleeding and infection at the site of the spinal injection and discomfort during block&#xD;
      placement. Relative to spinal anesthesia, general anesthesia may offer benefits of&#xD;
      hemodynamic stability. At present, while spinal anesthesia has been demonstrated in a&#xD;
      retrospective observational study to be associated with lower in-hospital mortality after hip&#xD;
      fracture (10), a meta-analysis of randomized trials was inconclusive with regard to mortality&#xD;
      differences. (9) Reflecting this state of clinical equipoise patterns of anesthesia care&#xD;
      differ widely by country and by provider, reflecting a large role of provider practice style&#xD;
      in determining anesthesia care for hip fracture. For example, in a recent survey of UK&#xD;
      anesthesiologists, 76% indicated that they routinely performed hip fracture surgeries with&#xD;
      spinal anesthesia (11). In contrast, recent U.S. data suggest that approximately 80% of hip&#xD;
      fracture surgeries are performed with general anesthesia, with wide variability in practice&#xD;
      across hospitals.(10) While these variations may in part reflect differences in patient&#xD;
      preferences, the current state of knowledge regarding the risks and benefits of differing&#xD;
      types of anesthesia is inadequate to support appropriately informed medical decision-making&#xD;
      by either patients or health care providers. The UKs national institute for Health and Care&#xD;
      Excellence (NICE) strongly recommend further clinical trials to provide additional&#xD;
      information regarding the clinical and cost effectiveness of differing anesthesia types for&#xD;
      hip fracture, stating that they were unable to identify any recent randomised controlled&#xD;
      trialsthat fully address this question and that the [available] evidence is old and does not&#xD;
      reflect current practice.&#xD;
&#xD;
      Study Design Phase II&#xD;
&#xD;
      Design This is a randomized, controlled trial of spinal versus general anesthesia to test the&#xD;
      effect of anesthesia type on rates of postoperative delirium after hip fracture surgery.&#xD;
&#xD;
      Study duration It is expected that this study will begin enrollment in June 2013. The&#xD;
      enrollment of all subjects is projected to be completed in May 2014 with data analysis to&#xD;
      follow. The study will hope to be completed by June 2015.&#xD;
&#xD;
      The length of participation for each subject will be about 5 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Postoperative Delirium After Hip Fracture Surgery</measure>
    <time_frame>Up to 5 days post hip fracture surgery</time_frame>
    <description>Delirium will be assessed by the Confusion Assessment Method Instrument (CAM), a validated method of assessing delirium based on the presence of both (1) an acute onset of signs and symptoms with a fluctuating course AND (2) inattention; PLUS (3) disorganized thinking OR (4) an altered level of consciousness.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Postoperative Complications</condition>
  <condition>Hip Fracture</condition>
  <condition>Delirium</condition>
  <arm_group>
    <arm_group_label>General endotracheal anesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard care general endotracheal anesthesia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regional (spinal) anesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard care spinal anesthesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>General endotracheal anesthesia</intervention_name>
    <description>General Anesthesia&#xD;
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.</description>
    <arm_group_label>General endotracheal anesthesia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Regional (spinal) Anesthesia</intervention_name>
    <description>Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed.</description>
    <arm_group_label>Regional (spinal) anesthesia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is aged 18 and older.&#xD;
&#xD;
          2. Subject is scheduled to undergo surgical treatment of an acute femoral neck or&#xD;
             pertrochanteric hip fracture.&#xD;
&#xD;
          3. Subject can speak English&#xD;
&#xD;
          4. Subject has ability to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has a pathological or periprosthetic fracture.&#xD;
&#xD;
          2. Subject has concurrent conditions anticipated at the time of admission to require&#xD;
             surgical treatment (e.g. multiple trauma, acute cholecystitis).&#xD;
&#xD;
          3. Subject has severe cognitive impairment, as evidenced by a Montreal Cognitive&#xD;
             Assessment Score (MOCA) of 15 or less.&#xD;
&#xD;
          4. Subject has clinical findings of delirium prior to surgery, as evidenced by a positive&#xD;
             Confusion Assessment Method (CAM) evaluation;&#xD;
&#xD;
          5. Subject has contraindications to spinal anesthesia or volatile general anesthetics.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark D Neuman</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hosptial of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>American Psychiatric Association. Delirium, Dementia, and Amnestic and Other Cognitive Disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision). Washington, D.C.: American Psychiatric Association; 2000.</citation>
  </reference>
  <reference>
    <citation>Russo CA, Elixhauser A. Hospitalizations in the Elderly Population, 2003. 2006 May. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Statistical Brief #6. Available from http://www.ncbi.nlm.nih.gov/books/NBK63501/</citation>
    <PMID>21938846</PMID>
  </reference>
  <reference>
    <citation>Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009 Apr;5(4):210-20. doi: 10.1038/nrneurol.2009.24.</citation>
    <PMID>19347026</PMID>
  </reference>
  <reference>
    <citation>Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998 Apr;13(4):234-42. doi: 10.1046/j.1525-1497.1998.00073.x.</citation>
    <PMID>9565386</PMID>
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  <reference>
    <citation>Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. doi: 10.1056/NEJMra052321. No abstract available. Erratum In: N Engl J Med. 2006 Apr 13;354(15):1655.</citation>
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    <citation>Blackman DK, Kamimoto LA, Smith SM. Overview: surveillance for selected public health indicators affecting older adults--United States. MMWR CDC Surveill Summ. 1999 Dec 17;48(8):1-6.</citation>
    <PMID>10634268</PMID>
  </reference>
  <reference>
    <citation>Hung WW, Egol KA, Zuckerman JD, Siu AL. Hip fracture management: tailoring care for the older patient. JAMA. 2012 May 23;307(20):2185-94. doi: 10.1001/jama.2012.4842.</citation>
    <PMID>22618926</PMID>
  </reference>
  <reference>
    <citation>Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000 Jun;48(6):618-24. doi: 10.1111/j.1532-5415.2000.tb04718.x.</citation>
    <PMID>10855596</PMID>
  </reference>
  <reference>
    <citation>Parker MJ, Handoll HH, Griffiths R. Anaesthesia for hip fracture surgery in adults. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD000521. doi: 10.1002/14651858.CD000521.pub2.</citation>
    <PMID>15494999</PMID>
  </reference>
  <reference>
    <citation>Neuman MD, Silber JH, Elkassabany NM, Ludwig JM, Fleisher LA. Comparative effectiveness of regional versus general anesthesia for hip fracture surgery in adults. Anesthesiology. 2012 Jul;117(1):72-92. doi: 10.1097/ALN.0b013e3182545e7c.</citation>
    <PMID>22713634</PMID>
  </reference>
  <reference>
    <citation>Sandby-Thomas M, Sullivan G, Hall JE. A national survey into the peri-operative anaesthetic management of patients presenting for surgical correction of a fractured neck of femur. Anaesthesia. 2008 Mar;63(3):250-8. doi: 10.1111/j.1365-2044.2007.05328.x.</citation>
    <PMID>18289230</PMID>
  </reference>
  <reference>
    <citation>National Clinical Guideline Centre (UK). The Management of Hip Fracture in Adults [Internet]. London: Royal College of Physicians (UK); 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK83014/</citation>
    <PMID>22420011</PMID>
  </reference>
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    <citation>Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, Mears SC. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010 Jan;85(1):18-26. doi: 10.4065/mcp.2009.0469. Erratum In: Mayo Clin Proc. 2010 Apr;85(4):400. Dosage error in article text.</citation>
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    <PMID>1202204</PMID>
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    <citation>Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8. doi: 10.7326/0003-4819-113-12-941.</citation>
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    <citation>Simon R. Restricted randomization designs in clinical trials. Biometrics. 1979 Jun;35(2):503-12.</citation>
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    <citation>Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138.</citation>
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    <citation>KATZ S, FORD AB, MOSKOWITZ RW, JACKSON BA, JAFFE MW. STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. JAMA. 1963 Sep 21;185:914-9. doi: 10.1001/jama.1963.03060120024016. No abstract available.</citation>
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    <citation>Inouye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti ME. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med. 1993 Sep 15;119(6):474-81. doi: 10.7326/0003-4819-119-6-199309150-00005.</citation>
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    <citation>Kahan BC, Morris TP. Improper analysis of trials randomised using stratified blocks or minimisation. Stat Med. 2012 Feb 20;31(4):328-40. doi: 10.1002/sim.4431. Epub 2011 Dec 4.</citation>
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  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <results_first_submitted>October 24, 2017</results_first_submitted>
  <results_first_submitted_qc>July 27, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2018</results_first_posted>
  <last_update_submitted>July 27, 2018</last_update_submitted>
  <last_update_submitted_qc>July 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Mark Neuman</investigator_full_name>
    <investigator_title>Assistant Professor of Anesthesiology and Critical Care</investigator_title>
  </responsible_party>
  <keyword>delirium</keyword>
  <keyword>hip fracture</keyword>
  <keyword>general anesthesia</keyword>
  <keyword>spinal anesthesia</keyword>
  <keyword>postoperative complications</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Postoperative Complications</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Hip Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 15 patients provided informed consent for participation; 3 were withdrawn from the study prior to randomization. 2 of these patients were withdrawn due to ineligibility; 1 was withdrawn due to other reasons.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>General Endotracheal Anesthesia</title>
          <description>Standard care general endotracheal anesthesia&#xD;
General endotracheal anesthesia: General Anesthesia&#xD;
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.</description>
        </group>
        <group group_id="P2">
          <title>Regional (Spinal) Anesthesia</title>
          <description>Standard care spinal anesthesia&#xD;
Regional (spinal) Anesthesia: Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed. Propofol dose will be titrated to achieve light to moderate sedation, defined as a Richmond Agitation/Sedation Scale (RASS) score of -1 to -318. In the event of block failure induction and maintenance of general endotracheal anesthesia will occur via the procedures outlined above. For all patients, post-operative pain management will be via hydromorphone PCA or PRN hydromorphone bolus, followed by oral oxycodone and acetaminophen.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>General Endotracheal Anesthesia</title>
          <description>Standard care general endotracheal anesthesia&#xD;
General endotracheal anesthesia: General Anesthesia&#xD;
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.</description>
        </group>
        <group group_id="B2">
          <title>Regional (Spinal) Anesthesia</title>
          <description>Standard care spinal anesthesia&#xD;
Regional (spinal) Anesthesia: Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed. Propofol dose will be titrated to achieve light to moderate sedation, defined as a Richmond Agitation/Sedation Scale (RASS) score of -1 to -318. In the event of block failure induction and maintenance of general endotracheal anesthesia will occur via the procedures outlined above. For all patients, post-operative pain management will be via hydromorphone PCA or PRN hydromorphone bolus, followed by oral oxycodone and acetaminophen.</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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.7" lower_limit="57" upper_limit="88"/>
                    <measurement group_id="B2" value="80.5" lower_limit="62" upper_limit="92"/>
                    <measurement group_id="B3" value="71.5" lower_limit="62" upper_limit="86"/>
                  </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="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Postoperative Delirium After Hip Fracture Surgery</title>
        <description>Delirium will be assessed by the Confusion Assessment Method Instrument (CAM), a validated method of assessing delirium based on the presence of both (1) an acute onset of signs and symptoms with a fluctuating course AND (2) inattention; PLUS (3) disorganized thinking OR (4) an altered level of consciousness.</description>
        <time_frame>Up to 5 days post hip fracture surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>General Endotracheal Anesthesia</title>
            <description>Standard care general endotracheal anesthesia&#xD;
General endotracheal anesthesia: General Anesthesia&#xD;
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.</description>
          </group>
          <group group_id="O2">
            <title>Regional (Spinal) Anesthesia</title>
            <description>Standard care spinal anesthesia&#xD;
Regional (spinal) Anesthesia: Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed. Propofol dose will be titrated to achieve light to moderate sedation, defined as a Richmond Agitation/Sedation Scale (RASS) score of -1 to -318. In the event of block failure induction and maintenance of general endotracheal anesthesia will occur via the procedures outlined above. For all patients, post-operative pain management will be via hydromorphone PCA or PRN hydromorphone bolus, followed by oral oxycodone and acetaminophen.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Postoperative Delirium After Hip Fracture Surgery</title>
          <description>Delirium will be assessed by the Confusion Assessment Method Instrument (CAM), a validated method of assessing delirium based on the presence of both (1) an acute onset of signs and symptoms with a fluctuating course AND (2) inattention; PLUS (3) disorganized thinking OR (4) an altered level of consciousness.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>General Endotracheal Anesthesia</title>
          <description>Standard care general endotracheal anesthesia&#xD;
General endotracheal anesthesia: General Anesthesia&#xD;
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.</description>
        </group>
        <group group_id="E2">
          <title>Regional (Spinal) Anesthesia</title>
          <description>Standard care spinal anesthesia&#xD;
Regional (spinal) Anesthesia: Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed. Propofol dose will be titrated to achieve light to moderate sedation, defined as a Richmond Agitation/Sedation Scale (RASS) score of -1 to -318. In the event of block failure induction and maintenance of general endotracheal anesthesia will occur via the procedures outlined above. For all patients, post-operative pain management will be via hydromorphone PCA or PRN hydromorphone bolus, followed by oral oxycodone and acetaminophen.</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </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>
    <limitations_and_caveats>This was a limited pilot study conducted to assess the feasibility of a larger randomized trial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Mark D Neuman</name_or_title>
      <organization>University of Pennsylvania School of Medicine</organization>
      <phone>2157467468</phone>
      <email>neumanm@mail.med.upenn.edu</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/NCT02190903
org study id: 818017
nct id: NCT02190903
lead sponsor: 
has dmc: Yes
This pilot project will address the gaps in knowledge regarding the effect of anesthetic
      technique on the risk of delirium through an adequately-powered trial employing standardized
      regimens for treatment and outcome assessment to test the hypothesis that use of spinal
      versus general anesthesia decreases the risk of delirium after hip fracture surgery.
Objectives Overall objectives Overall Objectives Specific Aims

        1. To compare the effect of spinal versus general anesthesia on rates of postoperative
           delirium after hip fracture surgery. We hypothesize that rates of delirium after hip
           fracture surgery will be lower among patients receiving spinal versus general
           anesthesia.

        2. To develop, field-test, and conduct a qualitative evaluation of protocols and procedures
           for a planned multicenter trial to test the association of anesthesia technique with
           survival and recovery of function in activities of daily living ambulatory ability at
           six months after hip fracture.

      Primary outcome variable(s) The primary outcome variable is the rate of delirium after hip
      fracture surgery.

      Background Delirium, or a disturbance of consciousness and a change in cognition that develop
      over a short period of time, (1) complicates 2.6 million hospitalizations among U.S. adults
      aged 65 or older each year. (2,3) Patients who experience delirium during hospitalization
      face increased risks morbidity, mortality, and functional disability. (4) Each year, delirium
      accounts for $6.9 billion in Medicare hospital expenditures. (5) Delirium occurs in 35% to
      65% of the 320,000 older U.S. adults hospitalized for hip fracture each year. (6) While
      adverse survival and functional outcomes are common after hip fracture, (7) a single episode
      of delirium doubles the odds of both new functional dependence and new ambulatory disability
      at six months after fracture, and triples the odds of death or new nursing home placement.
      (8) Compared to general endotracheal anesthesia, spinal anesthesia may decrease the incidence
      of postoperative delirium after hip fracture surgery. Small randomized trials of anesthesia
      type for hip fracture have suggested a 50% lower risk of acute confusion after hip fracture
      surgery with spinal anesthesia, (9) but the heterogeneity of outcome definitions and
      measurement strategies employed by past trials, along with their use of historical anesthesia
      practices limit their applicability to current practice.

      As a result of these limitations, clinical equipoise continues to exist regarding the optimal
      anesthetic technique for hip fracture care. Compared to general anesthesia, spinal anesthesia
      may offer potential benefits not limited to decreased delirium. These may include decreased
      intraoperative blood loss, and decreased risks of postoperative thromboembolic events,
      respiratory infections and malignant hyperthermia. At the same time, spinal anesthesia may be
      associated with greater hypotension than general anesthesia, and may carry small risks of
      bleeding and infection at the site of the spinal injection and discomfort during block
      placement. Relative to spinal anesthesia, general anesthesia may offer benefits of
      hemodynamic stability. At present, while spinal anesthesia has been demonstrated in a
      retrospective observational study to be associated with lower in-hospital mortality after hip
      fracture (10), a meta-analysis of randomized trials was inconclusive with regard to mortality
      differences. (9) Reflecting this state of clinical equipoise patterns of anesthesia care
      differ widely by country and by provider, reflecting a large role of provider practice style
      in determining anesthesia care for hip fracture. For example, in a recent survey of UK
      anesthesiologists, 76% indicated that they routinely performed hip fracture surgeries with
      spinal anesthesia (11). In contrast, recent U.S. data suggest that approximately 80% of hip
      fracture surgeries are performed with general anesthesia, with wide variability in practice
      across hospitals.(10) While these variations may in part reflect differences in patient
      preferences, the current state of knowledge regarding the risks and benefits of differing
      types of anesthesia is inadequate to support appropriately informed medical decision-making
      by either patients or health care providers. The UKs national institute for Health and Care
      Excellence (NICE) strongly recommend further clinical trials to provide additional
      information regarding the clinical and cost effectiveness of differing anesthesia types for
      hip fracture, stating that they were unable to identify any recent randomised controlled
      trialsthat fully address this question and that the [available] evidence is old and does not
      reflect current practice.

      Study Design Phase II

      Design This is a randomized, controlled trial of spinal versus general anesthesia to test the
      effect of anesthesia type on rates of postoperative delirium after hip fracture surgery.

      Study duration It is expected that this study will begin enrollment in June 2013. The
      enrollment of all subjects is projected to be completed in May 2014 with data analysis to
      follow. The study will hope to be completed by June 2015.

      The length of participation for each subject will be about 5 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Postoperative Delirium After Hip Fracture Surgery
time frame: Up to 5 days post hip fracture surgery
description: Delirium will be assessed by the Confusion Assessment Method Instrument (CAM), a validated method of assessing delirium based on the presence of both (1) an acute onset of signs and symptoms with a fluctuating course AND (2) inattention; PLUS (3) disorganized thinking OR (4) an altered level of consciousness.
arm group label: General endotracheal anesthesia
arm group type: Active Comparator
description: Standard care general endotracheal anesthesia
arm group label: Regional (spinal) anesthesia
arm group type: Active Comparator
description: Standard care spinal anesthesia
intervention type: Other
intervention name: General endotracheal anesthesia
description: General Anesthesia
Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.
arm group label: General endotracheal anesthesia
intervention type: Other
intervention name: Regional (spinal) Anesthesia
description: Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed.
arm group label: Regional (spinal) anesthesia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark D Neuman
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
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PMID: 21938846
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PMID: 10634268
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PMID: 22618926
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PMID: 10855596
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PMID: 15494999
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PMID: 22713634
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PMID: 18289230
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PMID: 22420011
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PMID: 20042557
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PMID: 22139891
responsible party type: Principal Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Mark Neuman
investigator title: Assistant Professor of Anesthesiology and Critical Care
mesh term: Delirium
mesh term: Postoperative Complications
mesh term: Fractures, Bone
mesh term: Hip Fractures
mesh term: Anesthetics
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This was a limited pilot study conducted to assess the feasibility of a larger randomized trial.
point of contact: 