<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/NCT02257580</url>
  </required_header>
  <id_info>
    <org_study_id>2014-303</org_study_id>
    <nct_id>NCT02257580</nct_id>
  </id_info>
  <brief_title>The Effect of Intravenous EACA on Blood Loss and Transfusion Requirements After Bilateral VRO</brief_title>
  <official_title>The Effect of Intravenous E-Aminocaproic Acid (EACA) on Blood Loss and Transfusion Requirements After Bilateral Varus Rotational Osteotomy (VRO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      E-Aminocaproic acid (EACA) is an anti-fibrinolytic agent that is used to decrease blood loss&#xD;
      and transfusion requirements after several orthopedic procedures. The aim of this prospective&#xD;
      double-blind placebo-controlled randomized trial is to determine whether IV EACA reduces&#xD;
      intra-operative calculated total blood loss in patients undergoing bilateral varus rotational&#xD;
      osteotomy (VRO). This study will also investigate intraoperative cell saver utilization,&#xD;
      transfusion of allogeneic blood, hospital length-of-stay (LOS), short term complications, and&#xD;
      long-term outcomes.This study will provide Level I evidence and has the potential to improve&#xD;
      outcomes in children undergoing this procedure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The participating anesthesiologists will not be blinded to study arms and hypotheses. Dr.&#xD;
      Christopher Edmonds will be the head anesthesiologist for this study and will administer&#xD;
      anesthetics to participants in this trial whenever his schedule makes it possible. Anesthesia&#xD;
      will be conducted in a standardized fashion, with IV sedation using Versed and IV propofol,&#xD;
      +/- Fentanyl and Ketamine . A Combined Spinal-Epidural (CSE) will be placed using 12.5-20 mg&#xD;
      of bupivacaine. If a CSE is unsuccessful and an epidural and/or spinal are successfully&#xD;
      obtained, the patient may still be included in the study. Patients not receiving neuraxial&#xD;
      anesthesia will be excluded. If a patient requires general anesthesia, it will be induced at&#xD;
      this time, but the patient will be excluded from the study. An arterial line and additional&#xD;
      venous access will be obtained in standardized sterile practice. Sedation will be maintained&#xD;
      with IV propofol. IV Valium, Toradol and IV acetaminophen will be given towards the end of&#xD;
      the case, per anesthesiologist's discretion.&#xD;
&#xD;
      The blood pressure target will be 20-25% below baseline, which will be achieved primarily&#xD;
      with the neuraxial anesthesia. For blood pressure above this range, the epidural will be&#xD;
      dosed with a short-acting local anesthetic, and/or IV sedation will be titrated as per the&#xD;
      anesthesiologist's judgment. For hypotension below this range, pressors or intravenous&#xD;
      pressors will be given. An IV fluid bolus may also be given in the amount of 10-20cc/kg.&#xD;
      Additional maintenance IV fluids will be given to maintain urine output of at least&#xD;
      0.5-1ml/kg/hr. The criteria for transfusion of blood products will be a hemoglobin level of &lt;&#xD;
      7.0 g/dL or a hemoglobin level of &lt; 10.0 g/dL with clinical signs of symptomatic anemia&#xD;
      (e.g., unexplained tachycardia, hypotension unresponsive to fluids or vasopressors, change in&#xD;
      mental status, low urine output, and shortness of breath). Blood will be administered 1 unit&#xD;
      at a time, and the presence of symptoms or signs will be reassessed after each unit. This&#xD;
      algorithm may be altered by the treating physician (e.g., PACU attending, surgeon, or the OR&#xD;
      anesthesiologist), however all decisions will be supported by reasonable documentation.&#xD;
      Drains will be removed on POD 2 unless specified by the attending surgeon. Of note, the chart&#xD;
      of the patient will clearly indicate him/her as a study patient; a sticker will be place on&#xD;
      the front of each participating patient's chart. Their enrollment will also be communicated&#xD;
      in the clinician rounding notes for each patient. Drains will be labeled for each study&#xD;
      participant as well, and nurses will record the drain outputs per their floor protocol.&#xD;
&#xD;
      Attending surgeons, orthopedic surgery residents, physician assistants and research&#xD;
      assistants involved with this study will assist in data collection. For each patient, we will&#xD;
      collect demographic data, pre-operative CBC data, intra-operative cell saver auto-transfusion&#xD;
      volumes, post-operative number of packed red blood cell units transfused, post-operative CBC&#xD;
      data, post-operative drain outputs, and post-operative complications. This information will&#xD;
      be gathered from the peri-operative medical records and electronic medical records. Surgeons&#xD;
      and clinical and research personnel will review medical chart and progress notes for evidence&#xD;
      of clinically significant VTE, reoperation, hematoma, seroma, and infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2015</start_date>
  <completion_date type="Actual">October 26, 2020</completion_date>
  <primary_completion_date type="Actual">October 26, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intraoperative Calculated Total Blood Loss</measure>
    <time_frame>Intraoperative (3-6 hours)</time_frame>
    <description>Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraoperative Cell Saver Utilization</measure>
    <time_frame>Intraoperative, 1 day</time_frame>
    <description>Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Allogeneic Blood Transfusion</measure>
    <time_frame>Post-Surgery, an expected average of 1 week</time_frame>
    <description>The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post Operative Blood Loss</measure>
    <time_frame>Post-Surgery, 24 hours</time_frame>
    <description>24 hour drain output (mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospital Stay</measure>
    <time_frame>Post-Surgery, an expected average of 1 week</time_frame>
    <description>postoperative day of discharge after surgery- day of intake.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death]</measure>
    <time_frame>an expected average of 1 week (post-surgery), Follow-up at 6 weeks</time_frame>
    <description>Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>E-Aminocaproic Acid</condition>
  <condition>Bilateral Varus Rotational Osteotomy</condition>
  <arm_group>
    <arm_group_label>E-Aminocaproic acid (EACA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E-Aminocaproic acid</intervention_name>
    <description>E-Aminocaproic acid (EACA) is a synthetic lysine analog that competitively inhibits the activation of plasminogen to plasmin and subsequently decreases the degree of fibrinolysis (Faraoni,2014} and is currently being used to decrease blood loss and transfusion requirements after orthopaedic procedures.(Eubanks,2010} Multiple meta analyses and retrospective and prospective studies have shown that EACA decreases blood loss and transfusion requirements after orthopaedic surgery{ McLeod,2013; Thompson, 2005; Thompson,2008; Gill,2008; Florentino-Pineda,2001}.Results from these studies also suggest that EACA will decreased post-operative morbidity, length of hospital stay, hospital costs, and complications.{Chimento,2013; Thompson,2005; Florentino-Pineda,2001}</description>
    <arm_group_label>E-Aminocaproic acid (EACA)</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>EACA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled for bilateral varus rotational osteotomy (VRO) with or without associated&#xD;
             soft tissue and osseous procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preoperative use of an anticoagulant (Plavix, warfarin, lovenox, etc.)&#xD;
&#xD;
          -  History of hypersensitivity to EACA&#xD;
&#xD;
          -  History of thromboembolic event (e.g., PE or DVT)&#xD;
&#xD;
          -  History of renal insufficiency or failure&#xD;
&#xD;
          -  Congenital or acquired coagulopathy as evidence by INR &gt;1.4 or PTT &gt; 1.4 times normal,&#xD;
             or Platelets &lt;150,000/mm3 on preoperative laboratory testing&#xD;
&#xD;
          -  Use of hormone replacement therapy or hormonal contraceptive agents within days prior&#xD;
             to surgery&#xD;
&#xD;
          -  Use of acetylsalicylic acid (ASA), antiplatelet agents within 7 days prior to surgery&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Not received neuraxial anesthesia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Scher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8.</citation>
    <PMID>20190103</PMID>
  </reference>
  <reference>
    <citation>Faraoni D, Goobie SM. The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature. Anesth Analg. 2014 Mar;118(3):628-36. doi: 10.1213/ANE.0000000000000080.</citation>
    <PMID>24557107</PMID>
  </reference>
  <reference>
    <citation>McLeod LM, French B, Flynn JM, Dormans JP, Keren R. Antifibrinolytic Use and Blood Transfusions in Pediatric Scoliosis Surgeries Performed at US Children's Hospitals. J Spinal Disord Tech. 2015 Oct;28(8):E460-6. doi: 10.1097/BSD.0b013e3182a22a54.</citation>
    <PMID>24091932</PMID>
  </reference>
  <reference>
    <citation>Thompson GH, Florentino-Pineda I, Poe-Kochert C. The role of amicar in decreasing perioperative blood loss in idiopathic scoliosis. Spine (Phila Pa 1976). 2005 Sep 1;30(17 Suppl):S94-9. doi: 10.1097/01.brs.0000175188.05542.a9.</citation>
    <PMID>16138073</PMID>
  </reference>
  <reference>
    <citation>Thompson GH, Florentino-Pineda I, Poe-Kochert C, Armstrong DG, Son-Hing J. Role of Amicar in surgery for neuromuscular scoliosis. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2623-9. doi: 10.1097/BRS.0b013e318187c046.</citation>
    <PMID>18981961</PMID>
  </reference>
  <reference>
    <citation>Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008 Nov;90(11):2399-407. doi: 10.2106/JBJS.G.01179.</citation>
    <PMID>18978408</PMID>
  </reference>
  <reference>
    <citation>Florentino-Pineda I, Blakemore LC, Thompson GH, Poe-Kochert C, Adler P, Tripi P. The Effect of epsilon-aminocaproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion: a preliminary prospective study. Spine (Phila Pa 1976). 2001 May 15;26(10):1147-51. doi: 10.1097/00007632-200105150-00011.</citation>
    <PMID>11413428</PMID>
  </reference>
  <reference>
    <citation>Chimento GF, Huff T, Ochsner JL Jr, Meyer M, Brandner L, Babin S. An evaluation of the use of topical tranexamic acid in total knee arthroplasty. J Arthroplasty. 2013 Sep;28(8 Suppl):74-7. doi: 10.1016/j.arth.2013.06.037.</citation>
    <PMID>24034510</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>August 12, 2022</results_first_submitted>
  <results_first_submitted_qc>November 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2022</results_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>E-Aminocaproic Acid</keyword>
  <keyword>Bilateral Varus Rotational Osteotomy</keyword>
  <keyword>Blood Loss and Transfusion</keyword>
  <keyword>Complications</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aminocaproic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 10, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT02257580/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 9, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT02257580/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients aged 18 or younger with CP indicated for bilateral VRO. Hx of a thromboembolic event, renal insufficiency or failure, known hypersensitivity to EACA, congenital or acquired coagulopathy, pts that could not receive neuraxial anesthesia, being treated with anticoagulants, hormone replacement therapy or hormonal contraceptive agent were excluded. Pts undergoing bilateral VRO were identified and screened by the study surgeons. 2 screened pts declined to participate, 2 did not qualify.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>E-Aminocaproic Acid (EACA)</title>
          <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="12"/>
              </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>E-Aminocaproic Acid (EACA)</title>
          <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Equivalent volume of normal saline prepared by the pharmacy.</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="16"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 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>
                  <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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="16"/>
                    <count group_id="B2" value="12"/>
                    <count group_id="B3" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Intraoperative Calculated Total Blood Loss</title>
        <description>Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss.</description>
        <time_frame>Intraoperative (3-6 hours)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Intraoperative Calculated Total Blood Loss</title>
          <description>Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss.</description>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="535.7" spread="356.6"/>
                    <measurement group_id="O2" value="628.0" spread="235.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intraoperative Cell Saver Utilization</title>
        <description>Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion.</description>
        <time_frame>Intraoperative, 1 day</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Intraoperative Cell Saver Utilization</title>
          <description>Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion.</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="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postoperative Allogeneic Blood Transfusion</title>
        <description>The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit.</description>
        <time_frame>Post-Surgery, an expected average of 1 week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Allogeneic Blood Transfusion</title>
          <description>The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit.</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="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post Operative Blood Loss</title>
        <description>24 hour drain output (mL)</description>
        <time_frame>Post-Surgery, 24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Post Operative Blood Loss</title>
          <description>24 hour drain output (mL)</description>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.5" spread="69.8"/>
                    <measurement group_id="O2" value="103.3" spread="91.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Hospital Stay</title>
        <description>postoperative day of discharge after surgery- day of intake.</description>
        <time_frame>Post-Surgery, an expected average of 1 week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Hospital Stay</title>
          <description>postoperative day of discharge after surgery- day of intake.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" lower_limit="4" upper_limit="7"/>
                    <measurement group_id="O2" value="5.1" lower_limit="4" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death]</title>
        <description>Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years)</description>
        <time_frame>an expected average of 1 week (post-surgery), Follow-up at 6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>E-Aminocaproic Acid (EACA)</title>
            <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Equivalent volume of normal saline prepared by the pharmacy.</description>
          </group>
        </group_list>
        <measure>
          <title>Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death]</title>
          <description>Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years)</description>
          <units>cases per 100,000 person years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day of surgery through 6 weeks post-op.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>E-Aminocaproic Acid (EACA)</title>
          <description>An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Equivalent volume of normal saline prepared by the pharmacy.</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </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>Colson Zucker, Research Coordinator</name_or_title>
      <organization>Hospital for Special Surgery</organization>
      <phone>6467146029</phone>
      <email>zuckerc@hss.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/NCT02257580
org study id: 2014-303
nct id: NCT02257580
lead sponsor: 
has dmc: Yes
E-Aminocaproic acid (EACA) is an anti-fibrinolytic agent that is used to decrease blood loss
      and transfusion requirements after several orthopedic procedures. The aim of this prospective
      double-blind placebo-controlled randomized trial is to determine whether IV EACA reduces
      intra-operative calculated total blood loss in patients undergoing bilateral varus rotational
      osteotomy (VRO). This study will also investigate intraoperative cell saver utilization,
      transfusion of allogeneic blood, hospital length-of-stay (LOS), short term complications, and
      long-term outcomes.This study will provide Level I evidence and has the potential to improve
      outcomes in children undergoing this procedure.
The participating anesthesiologists will not be blinded to study arms and hypotheses. Dr.
      Christopher Edmonds will be the head anesthesiologist for this study and will administer
      anesthetics to participants in this trial whenever his schedule makes it possible. Anesthesia
      will be conducted in a standardized fashion, with IV sedation using Versed and IV propofol,
      +/- Fentanyl and Ketamine . A Combined Spinal-Epidural (CSE) will be placed using 12.5-20 mg
      of bupivacaine. If a CSE is unsuccessful and an epidural and/or spinal are successfully
      obtained, the patient may still be included in the study. Patients not receiving neuraxial
      anesthesia will be excluded. If a patient requires general anesthesia, it will be induced at
      this time, but the patient will be excluded from the study. An arterial line and additional
      venous access will be obtained in standardized sterile practice. Sedation will be maintained
      with IV propofol. IV Valium, Toradol and IV acetaminophen will be given towards the end of
      the case, per anesthesiologist's discretion.

      The blood pressure target will be 20-25% below baseline, which will be achieved primarily
      with the neuraxial anesthesia. For blood pressure above this range, the epidural will be
      dosed with a short-acting local anesthetic, and/or IV sedation will be titrated as per the
      anesthesiologist's judgment. For hypotension below this range, pressors or intravenous
      pressors will be given. An IV fluid bolus may also be given in the amount of 10-20cc/kg.
      Additional maintenance IV fluids will be given to maintain urine output of at least
      0.5-1ml/kg/hr. The criteria for transfusion of blood products will be a hemoglobin level of <
      7.0 g/dL or a hemoglobin level of < 10.0 g/dL with clinical signs of symptomatic anemia
      (e.g., unexplained tachycardia, hypotension unresponsive to fluids or vasopressors, change in
      mental status, low urine output, and shortness of breath). Blood will be administered 1 unit
      at a time, and the presence of symptoms or signs will be reassessed after each unit. This
      algorithm may be altered by the treating physician (e.g., PACU attending, surgeon, or the OR
      anesthesiologist), however all decisions will be supported by reasonable documentation.
      Drains will be removed on POD 2 unless specified by the attending surgeon. Of note, the chart
      of the patient will clearly indicate him/her as a study patient; a sticker will be place on
      the front of each participating patient's chart. Their enrollment will also be communicated
      in the clinician rounding notes for each patient. Drains will be labeled for each study
      participant as well, and nurses will record the drain outputs per their floor protocol.

      Attending surgeons, orthopedic surgery residents, physician assistants and research
      assistants involved with this study will assist in data collection. For each patient, we will
      collect demographic data, pre-operative CBC data, intra-operative cell saver auto-transfusion
      volumes, post-operative number of packed red blood cell units transfused, post-operative CBC
      data, post-operative drain outputs, and post-operative complications. This information will
      be gathered from the peri-operative medical records and electronic medical records. Surgeons
      and clinical and research personnel will review medical chart and progress notes for evidence
      of clinically significant VTE, reoperation, hematoma, seroma, and infection.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Intraoperative Calculated Total Blood Loss
time frame: Intraoperative (3-6 hours)
description: Determined by estimated blood volume, calculated using difference in preoperative and postoperative hemoglobin and applied to the Nadler equation for estimating blood volume while adjusting for transfused hemoglobin to produce a single metric of calculated intraoperative blood loss.
measure: Intraoperative Cell Saver Utilization
time frame: Intraoperative, 1 day
description: Number of participants requiring 1 unit of intraoperative cell saver transfusion. Patients either received or did not receive intraoperative cell saver transfusion. The maximum number of intraoperative units transfused in this study was 1 unit. The count of participants in the data table refers to the number of patients who received this transfusion.
measure: Postoperative Allogeneic Blood Transfusion
time frame: Post-Surgery, an expected average of 1 week
description: The number of participants that required 1 unit of blood transfused post-operatively. Patients received blood if necessary post operatively, and the maximum number of units a patient received was 1. The count of participants refers to the number of patients who received this transfusion unit.
measure: Post Operative Blood Loss
time frame: Post-Surgery, 24 hours
description: 24 hour drain output (mL)
measure: Length of Hospital Stay
time frame: Post-Surgery, an expected average of 1 week
description: postoperative day of discharge after surgery- day of intake.
measure: Complications [VTE (Symptomatic of DVT or PE), Infection (Superficial, Deep), Hematoma, Seroma, Reoperation, and Death]
time frame: an expected average of 1 week (post-surgery), Follow-up at 6 weeks
description: Incidence of VTE (symptomatic of DVT or PE), infection (superficial, deep), hematoma, seroma, reoperation, and death, measured in person-years ( x cases per 100,000 person years)
arm group label: E-Aminocaproic acid (EACA)
arm group type: Experimental
description: An EACA loading dose of 100 mg/kg with a max of 4-5 grams will be given up to 1 hour prior to incision. During the case, an EACA infusion of 33 mg/kg/hr (max of 1 gram/hr) will be maintained. The use of EACA will be terminated at the end of the case.
arm group label: Placebo
arm group type: Placebo Comparator
description: Equivalent volume of normal saline prepared by the pharmacy.
intervention type: Drug
intervention name: E-Aminocaproic acid
description: E-Aminocaproic acid (EACA) is a synthetic lysine analog that competitively inhibits the activation of plasminogen to plasmin and subsequently decreases the degree of fibrinolysis (Faraoni,2014} and is currently being used to decrease blood loss and transfusion requirements after orthopaedic procedures.(Eubanks,2010} Multiple meta analyses and retrospective and prospective studies have shown that EACA decreases blood loss and transfusion requirements after orthopaedic surgery{ McLeod,2013; Thompson, 2005; Thompson,2008; Gill,2008; Florentino-Pineda,2001}.Results from these studies also suggest that EACA will decreased post-operative morbidity, length of hospital stay, hospital costs, and complications.{Chimento,2013; Thompson,2005; Florentino-Pineda,2001}
arm group label: E-Aminocaproic acid (EACA)
arm group label: Placebo
other name: EACA
criteria: 
gender: All
minimum age: 1 Year
maximum age: 18 Years
healthy volunteers: No
last name: David Scher, MD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
country: United States
citation: Eubanks JD. Antifibrinolytics in major orthopaedic surgery. J Am Acad Orthop Surg. 2010 Mar;18(3):132-8.
PMID: 20190103
citation: Faraoni D, Goobie SM. The efficacy of antifibrinolytic drugs in children undergoing noncardiac surgery: a systematic review of the literature. Anesth Analg. 2014 Mar;118(3):628-36. doi: 10.1213/ANE.0000000000000080.
PMID: 24557107
citation: McLeod LM, French B, Flynn JM, Dormans JP, Keren R. Antifibrinolytic Use and Blood Transfusions in Pediatric Scoliosis Surgeries Performed at US Children's Hospitals. J Spinal Disord Tech. 2015 Oct;28(8):E460-6. doi: 10.1097/BSD.0b013e3182a22a54.
PMID: 24091932
citation: Thompson GH, Florentino-Pineda I, Poe-Kochert C. The role of amicar in decreasing perioperative blood loss in idiopathic scoliosis. Spine (Phila Pa 1976). 2005 Sep 1;30(17 Suppl):S94-9. doi: 10.1097/01.brs.0000175188.05542.a9.
PMID: 16138073
citation: Thompson GH, Florentino-Pineda I, Poe-Kochert C, Armstrong DG, Son-Hing J. Role of Amicar in surgery for neuromuscular scoliosis. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2623-9. doi: 10.1097/BRS.0b013e318187c046.
PMID: 18981961
citation: Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008 Nov;90(11):2399-407. doi: 10.2106/JBJS.G.01179.
PMID: 18978408
citation: Florentino-Pineda I, Blakemore LC, Thompson GH, Poe-Kochert C, Adler P, Tripi P. The Effect of epsilon-aminocaproic acid on perioperative blood loss in patients with idiopathic scoliosis undergoing posterior spinal fusion: a preliminary prospective study. Spine (Phila Pa 1976). 2001 May 15;26(10):1147-51. doi: 10.1097/00007632-200105150-00011.
PMID: 11413428
citation: Chimento GF, Huff T, Ochsner JL Jr, Meyer M, Brandner L, Babin S. An evaluation of the use of topical tranexamic acid in total knee arthroplasty. J Arthroplasty. 2013 Sep;28(8 Suppl):74-7. doi: 10.1016/j.arth.2013.06.037.
PMID: 24034510
responsible party type: Sponsor
mesh term: Hemorrhage
mesh term: Aminocaproic Acid
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 