<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/NCT01681095</url>
  </required_header>
  <id_info>
    <org_study_id>2012-125</org_study_id>
    <nct_id>NCT01681095</nct_id>
  </id_info>
  <brief_title>Custodiol-HTK (Histidine-tryptophan-ketoglutarate) Solution as a Cardioplegic Agent</brief_title>
  <official_title>Custodiol-HTK Solution as a Cardioplegic Agent- A Prospective Non-Inferiority Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marc Sakwa, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Essential Pharmaceuticals, LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>William Beaumont Hospitals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold&#xD;
      cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic&#xD;
      arrest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to demonstrate that Custodiol is not inferior to cold&#xD;
      cardioplegic solution for myocardial protection by comparing standard cold blood cardioplegia&#xD;
      to Custodiol solution with respect to myocardial injury as measured by Creatine phosphokinase&#xD;
      MB isoenzyme (CK-MB),troponin-I at 7 hours post surgery and changes in ejection fraction by&#xD;
      trans-thoracic echocardiogram (TTE)or trans-esophageal echocardiogram (TEE) at 24 hours post&#xD;
      surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)</measure>
    <time_frame>Baseline and 7 hours post surgery</time_frame>
    <description>Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Troponin I</measure>
    <time_frame>Baseline and 7 hours post surgery</time_frame>
    <description>Troponin I values, difference from baseline 7 hours post surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)</measure>
    <time_frame>Baseline and 24 hours post surgery</time_frame>
    <description>LV ejection fraction by TTE, difference from baseline at 24 hours post surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiac Dysrhythmias</measure>
    <time_frame>up to 36 hrs post surgery</time_frame>
    <description>Number of participants with new or worsening of cardiac dysrhythmias</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Cause Mortality</measure>
    <time_frame>30 days post procedure</time_frame>
    <description>Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular Mortality</measure>
    <time_frame>30 days post procedure</time_frame>
    <description>Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time on Mechanically Assisted Ventilation</measure>
    <time_frame>up to 36 hours post procedure</time_frame>
    <description>time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Vasopressor / Inotropic Agent</measure>
    <time_frame>up to 36 hours post procedure</time_frame>
    <description>Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative Inotropic Infusion &gt;20 Minutes</measure>
    <time_frame>during operative procedure</time_frame>
    <description>Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive Care Unit (ICU) Length of Stay</measure>
    <time_frame>up to 100 days after admission</time_frame>
    <description>Duration of stay in ICU, from ICU admission to ICU discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Myocardial Infarction</measure>
    <time_frame>up to 36 hours post procedure</time_frame>
    <description>Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</measure>
    <time_frame>pre-operative</time_frame>
    <description>CK-MB measured pre-operatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</measure>
    <time_frame>24 hours post procedure</time_frame>
    <description>CK-MB measured 24 hours post-operatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</measure>
    <time_frame>48 hours post procedure</time_frame>
    <description>CK-MB measured 48 hours post-operatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Marker - Troponin-I</measure>
    <time_frame>pre-operatively</time_frame>
    <description>Troponin-I measured pre-operatively</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Marker - Troponin-I</measure>
    <time_frame>24 hours post procedure</time_frame>
    <description>Troponin-I measured 24 hours post-operative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Marker - Troponin-I</measure>
    <time_frame>48 hours post procedure</time_frame>
    <description>Troponin-I measured 48 hours post-operative</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Myocardial Ischemia</condition>
  <condition>Coronary Disease</condition>
  <condition>Heart Diseases</condition>
  <condition>Valvular Heart Disease</condition>
  <arm_group>
    <arm_group_label>Cardioplegia: Custodiol HTK Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cold Blood Cardioplegia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Custodiol HTK</intervention_name>
    <description>After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 10°C.</description>
    <arm_group_label>Cardioplegia: Custodiol HTK Solution</arm_group_label>
    <other_name>Histidine-tryptophan-ketoglutarate cardioplegia solution</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cold Blood Cardioplegia</intervention_name>
    <description>After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
    <arm_group_label>Cold Blood Cardioplegia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing scheduled cardiac surgery requiring cardioplegic arrest with&#xD;
             expected cross clamp time&gt;45 minutes&#xD;
&#xD;
          -  Patients age 18 and older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women*&#xD;
&#xD;
          -  Urgent or emergent cases&#xD;
&#xD;
          -  Repeat cardiovascular surgical procedures&#xD;
&#xD;
          -  Patients on dialysis&#xD;
&#xD;
          -  Any known allergies to components of either cardioplegia solution *All women of child&#xD;
             bearing potential must have a negative serum or urine pregnancy test.&#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>Marc Sakwa, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beaumont Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>William Beaumont Hospital</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Braathen B, Jeppsson A, Schersten H, Hagen OM, Vengen O, Rexius H, Lepore V, Tonnessen T. One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: a prospective randomized study. J Thorac Cardiovasc Surg. 2011 Apr;141(4):995-1001. doi: 10.1016/j.jtcvs.2010.07.011. Epub 2010 Aug 30.</citation>
    <PMID>20800244</PMID>
  </reference>
  <reference>
    <citation>Careaga G, Salazar D, Tellez S, Sanchez O, Borrayo G, Arguero R. Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients. Arch Med Res. 2001 Jul-Aug;32(4):296-9. doi: 10.1016/s0188-4409(01)00296-x.</citation>
    <PMID>11440787</PMID>
  </reference>
  <reference>
    <citation>Hachida M, Ookado A, Nonoyama M, Koyanagi H. Effect of HTK solution for myocardial preservation. J Cardiovasc Surg (Torino). 1996 Jun;37(3):269-74.</citation>
    <PMID>8698763</PMID>
  </reference>
  <reference>
    <citation>Yang Q, He GW. Effect of cardioplegic and organ preservation solutions and their components on coronary endothelium-derived relaxing factors. Ann Thorac Surg. 2005 Aug;80(2):757-67. doi: 10.1016/j.athoracsur.2004.10.003.</citation>
    <PMID>16039259</PMID>
  </reference>
  <reference>
    <citation>Beyersdorf F, Krause E, Sarai K, Sieber B, Deutschlander N, Zimmer G, Mainka L, Probst S, Zegelman M, Schneider W, et al. Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery. Thorac Cardiovasc Surg. 1990 Feb;38(1):20-9. doi: 10.1055/s-2007-1013985.</citation>
    <PMID>2106735</PMID>
  </reference>
  <reference>
    <citation>Savini C, Camurri N, Castelli A, Dell'Amore A, Pacini D, Suarez SM, Grillone G, Di Bartolomeo R. Myocardial protection using HTK solution in minimally invasive mitral valve surgery. Heart Surg Forum. 2005;8(1):E25-7. doi: 10.1532/HSF98.20041145.</citation>
    <PMID>15769709</PMID>
  </reference>
  <reference>
    <citation>Braathen B, Tonnessen T. Cold blood cardioplegia reduces the increase in cardiac enzyme levels compared with cold crystalloid cardioplegia in patients undergoing aortic valve replacement for isolated aortic stenosis. J Thorac Cardiovasc Surg. 2010 Apr;139(4):874-80. doi: 10.1016/j.jtcvs.2009.05.036. Epub 2009 Jul 26.</citation>
    <PMID>19660338</PMID>
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  <reference>
    <citation>Hendrikx M, Jiang H, Gutermann H, Toelsie J, Renard D, Briers A, Pauwels JL, Mees U. Release of cardiac troponin I in antegrade crystalloid versus cold blood cardioplegia. J Thorac Cardiovasc Surg. 1999 Sep;118(3):452-9. doi: 10.1016/s0022-5223(99)70182-0.</citation>
    <PMID>10469959</PMID>
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  <reference>
    <citation>Aarsaether E, Stenberg TA, Jakobsen O, Busund R. Mechanoenergetic function and troponin T release following cardioplegic arrest induced by St Thomas' and histidine-tryptophan-ketoglutarate cardioplegia--an experimental comparative study in pigs. Interact Cardiovasc Thorac Surg. 2009 Oct;9(4):635-9. doi: 10.1510/icvts.2009.208231. Epub 2009 Jul 23.</citation>
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  <reference>
    <citation>Gallandat Huet RC, Karliczek GF, van der Heide JN, Brenken U, Mooi B, van der Broeke JJ, Jenkins I, de Geus AF. Clinical effect of Bretschneider-HTK and St. Thomas cardioplegia on hemodynamic performance after bypass measured using an automatic datalogging database system. Thorac Cardiovasc Surg. 1988 Jun;36(3):151-6. doi: 10.1055/s-2007-1020064.</citation>
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    <citation>Arslan A, Sezgin A, Gultekin B, Ozkan S, Akay T, Uguz E, Tasdelen A, Aslamaci S. Low-dose histidine-tryptophan-ketoglutarate solution for myocardial protection. Transplant Proc. 2005 Sep;37(7):3219-22. doi: 10.1016/j.transproceed.2005.08.020.</citation>
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    <citation>Fannelop T, Dahle GO, Salminen PR, Moen CA, Matre K, Mongstad A, Eliassen F, Segadal L, Grong K. Multidose cold oxygenated blood is superior to a single dose of Bretschneider HTK-cardioplegia in the pig. Ann Thorac Surg. 2009 Apr;87(4):1205-13. doi: 10.1016/j.athoracsur.2009.01.041.</citation>
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    <citation>Schaper J, Scheld HH, Schmidt U, Hehrlein F. Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart. J Thorac Cardiovasc Surg. 1986 Jul;92(1):47-55.</citation>
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    <citation>Bical OM, Fromes Y, Paumier D, Gaillard D, Foiret JC, Trivin F. Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery? Cardiovasc Surg. 2001 Apr;9(2):188-93. doi: 10.1016/s0967-2109(00)00087-9.</citation>
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    <citation>Asano H, Kyo S, Ogiwara M, Tsunemoto M, Yokote Y, Omoto R, Koike K, Kobayashi T, Kobayashi J, Taketazu M. [Single-dose and high-volume Bretschneider cardioplegic solution for congenital heart surgery]. Kyobu Geka. 1999 Jan;52(1):82-6. Japanese.</citation>
    <PMID>10024809</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <results_first_submitted>April 26, 2016</results_first_submitted>
  <results_first_submitted_qc>January 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 1, 2017</results_first_posted>
  <last_update_submitted>July 23, 2019</last_update_submitted>
  <last_update_submitted_qc>July 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>William Beaumont Hospitals</investigator_affiliation>
    <investigator_full_name>Marc Sakwa, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Physiological Effects of Drugs</keyword>
  <keyword>Cardiovascular Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Mannitol</keyword>
  <keyword>Cardiac Surgery</keyword>
  <keyword>Cardioplegic Solutions</keyword>
  <keyword>HTK solution</keyword>
  <keyword>Myocardial protection</keyword>
  <keyword>Coronary Artery Disease</keyword>
  <keyword>Myocardial Ischemia</keyword>
  <keyword>Coronary Disease</keyword>
  <keyword>Heart Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tryptophan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cardioplegia: Custodiol HTK Solution</title>
          <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
        </group>
        <group group_id="P2">
          <title>Cold Blood Cardioplegia</title>
          <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="55"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="55"/>
              </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>Standard Cold Blood Cardioplegia</title>
          <description>55 participants were randomized to Standard cold blood cardioplegia. Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
        </group>
        <group group_id="B2">
          <title>Custiodiol HTK</title>
          <description>55 participants were randomized to Custodiol HTK. Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</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="55"/>
            <count group_id="B2" value="55"/>
            <count group_id="B3" value="110"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70" spread="11"/>
                    <measurement group_id="B2" value="63" spread="13"/>
                    <measurement group_id="B3" value="66" spread="12"/>
                  </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="20"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)</title>
        <description>Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery</description>
        <time_frame>Baseline and 7 hours post surgery</time_frame>
        <population>Patients for which both baseline and 7 hours post surgery values were available</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)</title>
          <description>Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery</description>
          <population>Patients for which both baseline and 7 hours post surgery values were available</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8" lower_limit="12.5" upper_limit="24"/>
                    <measurement group_id="O2" value="22.2" lower_limit="15" upper_limit="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Troponin I</title>
        <description>Troponin I values, difference from baseline 7 hours post surgery</description>
        <time_frame>Baseline and 7 hours post surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Troponin I</title>
          <description>Troponin I values, difference from baseline 7 hours post surgery</description>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.65" lower_limit="5.47" upper_limit="16.00"/>
                    <measurement group_id="O2" value="10.15" lower_limit="6.04" upper_limit="19.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)</title>
        <description>LV ejection fraction by TTE, difference from baseline at 24 hours post surgery</description>
        <time_frame>Baseline and 24 hours post surgery</time_frame>
        <population>patients for whom both preoperative and 24 hour LV ejection fractions were obtained</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)</title>
          <description>LV ejection fraction by TTE, difference from baseline at 24 hours post surgery</description>
          <population>patients for whom both preoperative and 24 hour LV ejection fractions were obtained</population>
          <units>% LV volume</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="11"/>
                    <measurement group_id="O2" value="1.9" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cardiac Dysrhythmias</title>
        <description>Number of participants with new or worsening of cardiac dysrhythmias</description>
        <time_frame>up to 36 hrs post surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac Dysrhythmias</title>
          <description>Number of participants with new or worsening of cardiac dysrhythmias</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>All Cause Mortality</title>
        <description>Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
        <time_frame>30 days post procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>All Cause Mortality</title>
          <description>Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </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>
        <type>Secondary</type>
        <title>Cardiovascular Mortality</title>
        <description>Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
        <time_frame>30 days post procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiovascular Mortality</title>
          <description>Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </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>
        <type>Secondary</type>
        <title>Time on Mechanically Assisted Ventilation</title>
        <description>time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.</description>
        <time_frame>up to 36 hours post procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Time on Mechanically Assisted Ventilation</title>
          <description>time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.</description>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" lower_limit="9.1" upper_limit="13.9"/>
                    <measurement group_id="O2" value="11.4" lower_limit="3.9" upper_limit="527"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Vasopressor / Inotropic Agent</title>
        <description>Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine</description>
        <time_frame>up to 36 hours post procedure</time_frame>
        <population>Patients not receiving any vasopressors are excluded from this analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Vasopressor / Inotropic Agent</title>
          <description>Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine</description>
          <population>Patients not receiving any vasopressors are excluded from this analysis</population>
          <units>minutes</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="340" lower_limit="115" upper_limit="636"/>
                    <measurement group_id="O2" value="582" lower_limit="154" upper_limit="1182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Postoperative Inotropic Infusion &gt;20 Minutes</title>
        <description>Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.</description>
        <time_frame>during operative procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Inotropic Infusion &gt;20 Minutes</title>
          <description>Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                    <measurement group_id="O2" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intensive Care Unit (ICU) Length of Stay</title>
        <description>Duration of stay in ICU, from ICU admission to ICU discharge</description>
        <time_frame>up to 100 days after admission</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Intensive Care Unit (ICU) Length of Stay</title>
          <description>Duration of stay in ICU, from ICU admission to ICU discharge</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="5"/>
                    <measurement group_id="O2" value="3" lower_limit="2" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Myocardial Infarction</title>
        <description>Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.</description>
        <time_frame>up to 36 hours post procedure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Myocardial Infarction</title>
          <description>Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="55"/>
              </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>
        <type>Secondary</type>
        <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
        <description>CK-MB measured pre-operatively</description>
        <time_frame>pre-operative</time_frame>
        <population>Only patients for whom preoperative CK-MB levels were available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
          <description>CK-MB measured pre-operatively</description>
          <population>Only patients for whom preoperative CK-MB levels were available were analyzed</population>
          <units>ng/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="38"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="1.2"/>
                    <measurement group_id="O2" value="2.6" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
        <description>CK-MB measured 24 hours post-operatively</description>
        <time_frame>24 hours post procedure</time_frame>
        <population>Only patients for whom 24 hour CK-MB values were available were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
          <description>CK-MB measured 24 hours post-operatively</description>
          <population>Only patients for whom 24 hour CK-MB values were available were analyzed</population>
          <units>ng/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="53"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20" spread="14"/>
                    <measurement group_id="O2" value="24" spread="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
        <description>CK-MB measured 48 hours post-operatively</description>
        <time_frame>48 hours post procedure</time_frame>
        <population>Only patients for whom 48 hour CK-MB values are available are included in analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)</title>
          <description>CK-MB measured 48 hours post-operatively</description>
          <population>Only patients for whom 48 hour CK-MB values are available are included in analysis</population>
          <units>ng/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="49"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="5.1"/>
                    <measurement group_id="O2" value="7.8" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cardiac Marker - Troponin-I</title>
        <description>Troponin-I measured pre-operatively</description>
        <time_frame>pre-operatively</time_frame>
        <population>Only patients for whom preoperative Troponin-I values were available were included in analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac Marker - Troponin-I</title>
          <description>Troponin-I measured pre-operatively</description>
          <population>Only patients for whom preoperative Troponin-I values were available were included in analysis</population>
          <units>ng/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="52"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".03" spread=".01"/>
                    <measurement group_id="O2" value=".03" spread=".01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cardiac Marker - Troponin-I</title>
        <description>Troponin-I measured 24 hours post-operative</description>
        <time_frame>24 hours post procedure</time_frame>
        <population>Only patients for whom 24-hour Troponin-I values were available were included in analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac Marker - Troponin-I</title>
          <description>Troponin-I measured 24 hours post-operative</description>
          <population>Only patients for whom 24-hour Troponin-I values were available were included in analysis</population>
          <units>ng/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="54"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="5.4"/>
                    <measurement group_id="O2" value="7.8" spread="8.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cardiac Marker - Troponin-I</title>
        <description>Troponin-I measured 48 hours post-operative</description>
        <time_frame>48 hours post procedure</time_frame>
        <population>Only patients for whom 48-hour Troponin-I values were available were included in analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Cardioplegia: Custodiol HTK Solution</title>
            <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
          </group>
          <group group_id="O2">
            <title>Cold Blood Cardioplegia</title>
            <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac Marker - Troponin-I</title>
          <description>Troponin-I measured 48 hours post-operative</description>
          <population>Only patients for whom 48-hour Troponin-I values were available were included in analysis</population>
          <units>ng/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="49"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="3.3"/>
                    <measurement group_id="O2" value="4.8" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were evaluated from time of consent to 4 days after surgery.</time_frame>
      <desc>An assessment of medical records and case report forms were examined for AEs or SAEs. Reports were reviewed by the PI for accuracy and relation to study intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cardioplegia: Custodiol HTK Solution</title>
          <description>Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.&#xD;
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.</description>
        </group>
        <group group_id="E2">
          <title>Cold Blood Cardioplegia</title>
          <description>Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.&#xD;
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional &gt; 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>No source vocabulary</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="55"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Profuse bleeding</sub_title>
                <description>Approximately 2 hours post-op the subject returned to the OR for re-exploration, finding right ventricular tear. This event was unexpected, and no action was taken with repect to the study drug.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute chest pain, shortness of breath</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>ER via EMS, L sided chest pain and SOB. Cardiac eval performed. ECG, chest x-ray and labs normal. Admitted for evaluation; the condition resolved. SAE due to hospitalization; unexpected, not related to drug, probably related to underlying disease.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Atrial Fib with rapid ventricular response</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>PO day 8, EC visit for weakness, ECG demonstrates A-fib w/RVR. Remained in observation, sx resolving within24 hours.SAE due to hospitalization, possibly r/t cardioplegia and possibly underlying disease, unexpected event</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Emergent Coronary Bypass</sub_title>
                <description>Hypoxia, hypotension following MVR. Treated 2 vessels via full sternotomy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>SOB, peripheral edema, mouth pain 16 days post-op</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Subject to ER via EMS. Con-med: Levaquin for pneumonia. Con-med change after evaluation. Resolving after 14days. Possibly r/t study compound, and an unexpected event.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>Direct admit from follow-up appt. Fatigue, R groin incision weeping, Atrial flutter w/RVR. Con-med change for incision. Cardioversion. SAE for hospitalization. Resolved and doubtful related to study compound, possible underlying disease.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory failure</sub_title>
                <description>Dx 2 days post-op requiring reintubation on 12/19/2012, resolving 1/17/2013, considered an SAE due to prolonged hospitalization, impairment of body structure or body function (Trach on 12/23/2012), unexpected, possibly related to underlying disease.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Community acquired pneumonia</sub_title>
                <description>ER presentation with hospital admission. Chest x-ray confirming dx. Con-med change. SAE due to hospitalization, not related to study compound, possibly related to underlying disease, unexpected event</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <description>Requiring vent support due to not able to extubate. SAE d/t prolonged hospitalization, not related to study compound, related to underlying disease, an unexpected event.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Mediastinal bleed</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Mediastinal bleed repaired day of surgery and considered resolved. Not related to treatment, possible related to underlying disease and unexpected.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>CVA</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>1 day post-op, head CT for stroke like sx showing acute cerebral infarct. Con-med changes for L Carotid 30-50% narrowing. Not related to study compound, not related to underlying disease, unexpected. Resolved with sequelae within 9 days.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Femoral occlusion</sub_title>
                <description>c/o leg pain, decreased peripheral pulse. 8 days PO performed femoral endarterectomy. Not related to study compound, not related to underlying disease and an unexpected event</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>No source vocabulary</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="55"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Trombocytopenia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="55"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Acute blood loss anemina/any anemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="55"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>A-Fib or fA-Flutter</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="14" subjects_affected="14" subjects_at_risk="55"/>
                <counts group_id="E2" events="21" subjects_affected="21" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Heart Block (complete, 1st AV, 2 AV, 3 AV)</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="55"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Junctional Rhythm</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="55"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Failure/Renal Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="55"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Bleeding (any)</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="55"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="55"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Adverse events (not serious adverse events) are listed only for events occurring with greater than 5% frequency in at least one of the groups.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Marc P. Sakwa, M.D.</name_or_title>
      <organization>William Beaumont Hospital</organization>
      <phone>248/898-0123</phone>
      <email>marc.sakwa@beaumont.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01681095
org study id: 2012-125
nct id: NCT01681095
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of the study is to demonstrate that Custodiol-HTK is not inferior to cold
      cardioplegic solution in patients undergoing cardiovascular surgery requiring cardioplegic
      arrest.
The objective of this study is to demonstrate that Custodiol is not inferior to cold
      cardioplegic solution for myocardial protection by comparing standard cold blood cardioplegia
      to Custodiol solution with respect to myocardial injury as measured by Creatine phosphokinase
      MB isoenzyme (CK-MB),troponin-I at 7 hours post surgery and changes in ejection fraction by
      trans-thoracic echocardiogram (TTE)or trans-esophageal echocardiogram (TEE) at 24 hours post
      surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Creatine Phosphokinase-MB Isoenzyme (CK-MB)
time frame: Baseline and 7 hours post surgery
description: Creatine phosphokinase MB isoenzyme (CK-MB) difference from baseline 7 hours post surgery
measure: Change in Troponin I
time frame: Baseline and 7 hours post surgery
description: Troponin I values, difference from baseline 7 hours post surgery
measure: Changes in Left Ventricular (LV) Ejection Fraction (EF) by Transthoracic Echocardiogram (TTE)
time frame: Baseline and 24 hours post surgery
description: LV ejection fraction by TTE, difference from baseline at 24 hours post surgery
measure: Cardiac Dysrhythmias
time frame: up to 36 hrs post surgery
description: Number of participants with new or worsening of cardiac dysrhythmias
measure: All Cause Mortality
time frame: 30 days post procedure
description: Number of participants with all-cause mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative
measure: Cardiovascular Mortality
time frame: 30 days post procedure
description: Number of participants with cardiovascular-related mortality AS reported in the Society of Thoracic Surgeons (STS) database after 30 days postoperative
measure: Time on Mechanically Assisted Ventilation
time frame: up to 36 hours post procedure
description: time in hours from intubation to extubation, with intervening transport to the cardiac critical care unit.
measure: Duration of Vasopressor / Inotropic Agent
time frame: up to 36 hours post procedure
description: Total time in minutes on any vasopressor or inotropic agent, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine
measure: Postoperative Inotropic Infusion >20 Minutes
time frame: during operative procedure
description: Number of patients receiving vasopressor or inotropic infusion for greater than 20 minutes in the operating room, including norepinephrine, epinephrine, vasopressin, milrinone, dobutamine, dopamine and/or neo-synephrine.
measure: Intensive Care Unit (ICU) Length of Stay
time frame: up to 100 days after admission
description: Duration of stay in ICU, from ICU admission to ICU discharge
measure: Myocardial Infarction
time frame: up to 36 hours post procedure
description: Number or participants fulfilling at least two of the following 3 criteria: (1) CK-MB of 100 ug/L or more and/or troponin-I of 3.0 ug/L or more, (2) appearance of new postoperative Q waves on the EKG of more than 0.03 seconds, and (3) a new hypokinetic or akinetic area in the left or right ventricle by echocardiography.
measure: Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
time frame: pre-operative
description: CK-MB measured pre-operatively
measure: Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
time frame: 24 hours post procedure
description: CK-MB measured 24 hours post-operatively
measure: Biochemical Marker - Creatine Kinase MB Isoenzyme (CK-MB)
time frame: 48 hours post procedure
description: CK-MB measured 48 hours post-operatively
measure: Cardiac Marker - Troponin-I
time frame: pre-operatively
description: Troponin-I measured pre-operatively
measure: Cardiac Marker - Troponin-I
time frame: 24 hours post procedure
description: Troponin-I measured 24 hours post-operative
measure: Cardiac Marker - Troponin-I
time frame: 48 hours post procedure
description: Troponin-I measured 48 hours post-operative
arm group label: Cardioplegia: Custodiol HTK Solution
arm group type: Experimental
description: Custodiol HTK (histidine-tryptophan-ketoglutarate) cardioplegia: One liter of HTK solution (Custodiol; Koehler Chemi, Alsbach-Haenlien, Germany) contains the following components: 15 mmol/L sodium chloride, 9 mmol/L potassium chloride, 4 mmol/L magnesium chloride, 18 mmol/L histidine hydrochloride, 180 mmol/L histidine, 2 mmol/L tryptophan, 30 mmol/L mannitol, 0.015 mmol/L calcium chloride, 1 mmol/L potassium hydrogen 2-ketoglutarate, osmolarity 310 mOsm/kg, pH 7.02-7.20.
Custodiol-HTK was delivered to establish and maintain cardiac arrest. After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. Custodiol-HTK was delivered at a temperature of 4°C - 10°C.
arm group label: Cold Blood Cardioplegia
arm group type: Active Comparator
description: Cold Blood Cardioplegia: One liter of cold blood cardioplegic solution, mixed at a ratio of 4:1 per Beaumont standard of care (blood /cardioplegic solution), contains the following in a 500 cc bag of D5W (dextrose 5% in water): 50meq/L potassium chloride, 37.5 meq/L sodium bicarbonate and 7.5 meq/L magnesium sulfate.
After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
intervention type: Drug
intervention name: Custodiol HTK
description: After cross-clamping of the aorta approximately 1-2 L of Custodiol-HTK was infused into the ascending aorta over 6-8 minutes. Additional doses of 100-200 ml were administered as needed. The cardioplegic solution was delivered at a temperature of 4°C - 10°C.
arm group label: Cardioplegia: Custodiol HTK Solution
other name: Histidine-tryptophan-ketoglutarate cardioplegia solution
intervention type: Drug
intervention name: Cold Blood Cardioplegia
description: After cross-clamping the aorta, at least 1000 mL of a 4:1 mixture of cold blood: cold crystalloid was administered at a pressure of 300 mmHg or less via a twin roller pump. Every 20 minutes an additional > 200 mL was administered in an antegrade/retrograde fashion throughout the remainder of the case. The cardioplegic solution was delivered at a temperature of 4°C - 8°C.
arm group label: Cold Blood Cardioplegia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Sakwa, M.D.
role: Principal Investigator
affiliation: Beaumont Health System
facility: 
country: United States
citation: Braathen B, Jeppsson A, Schersten H, Hagen OM, Vengen O, Rexius H, Lepore V, Tonnessen T. One single dose of histidine-tryptophan-ketoglutarate solution gives equally good myocardial protection in elective mitral valve surgery as repetitive cold blood cardioplegia: a prospective randomized study. J Thorac Cardiovasc Surg. 2011 Apr;141(4):995-1001. doi: 10.1016/j.jtcvs.2010.07.011. Epub 2010 Aug 30.
PMID: 20800244
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responsible party type: Sponsor-Investigator
investigator affiliation: William Beaumont Hospitals
investigator full name: Marc Sakwa, MD
investigator title: Principal Investigator
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Heart Diseases
mesh term: Heart Valve Diseases
mesh term: Ischemia
mesh term: Tryptophan
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Adverse events (not serious adverse events) are listed only for events occurring with greater than 5% frequency in at least one of the groups.
point of contact: 