<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/NCT01662856</url>
  </required_header>
  <id_info>
    <org_study_id>IG1101</org_study_id>
    <nct_id>NCT01662856</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Peripheral Vascular Surgery</brief_title>
  <official_title>A Prospective, Single-blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) as an Adjunct to Hemostasis During Peripheral Vascular Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Grifols, S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grifols Biologicals, LLC</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate that the application of Fibrin Sealant Grifols&#xD;
      provides a measurable benefit when compared to hemostasis achieved through conventional&#xD;
      surgical technique (suture) and by standard hemostatic action, such as mechanical pressure&#xD;
      through manual compression. This study has a Preliminary Part (I) in which all subjects are&#xD;
      treated with Fibrin Sealant Grifols and a Primary Part (II) in which subjects are randomized&#xD;
      in a 2:1 ratio to either Fibrin Sealant Grifols or manual compression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start</measure>
    <time_frame>From start of treatment until 4 minutes after treatment start</time_frame>
    <description>Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Hemostasis (TTH)</measure>
    <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
    <description>Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start.&#xD;
In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated.&#xD;
All calculations were performed using SAS PROC LIFETEST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points</measure>
    <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
    <description>Cumulative proportion of subjects having achieved hemostasis by each of the following time points:&#xD;
At 5 minutes following start of study treatment&#xD;
At 7 minutes following start of study treatment&#xD;
At 10 minutes following start of study treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of Treatment Failures</measure>
    <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
    <description>Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">225</enrollment>
  <condition>Vascular Surgical Bleeding</condition>
  <arm_group>
    <arm_group_label>Fibrin Sealant Grifols</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Manual Compression</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fibrin Sealant Grifols</intervention_name>
    <description>Combination of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).</description>
    <arm_group_label>Fibrin Sealant Grifols</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Manual Compression</intervention_name>
    <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
    <arm_group_label>Manual Compression</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline (within 24 hours prior to surgical procedure).&#xD;
&#xD;
          -  Require elective (non-emergency), primary, open (non-laparoscopic; non-endovascular)&#xD;
             peripheral vascular surgery.&#xD;
&#xD;
          -  Require one of the following peripheral vascular procedures involving proximal&#xD;
             end-to-side arterial anastomosis utilizing coated or uncoated Polytetrafluoroethylene&#xD;
             grafts: a) Femoral-femoral bypass grafting, b) Femoral-popliteal bypass grafting, c)&#xD;
             Femoral-distal bypass grafting, d) Ilio-iliac bypass grafting, e) Ilio-femoral bypass&#xD;
             grafting, f) Ilio-popliteal bypass grafting, g) Aorto-iliac bypass grafting, h)&#xD;
             Aorto-femoral bypass grafting, i)Axillo-femoral bypass grafting, and j) Upper&#xD;
             extremity vascular access for hemodialysis.&#xD;
&#xD;
          -  A target bleeding site can be identified.&#xD;
&#xD;
          -  Target bleeding site has moderate arterial bleeding.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Undergoing a re-operative procedure.&#xD;
&#xD;
          -  Undergoing other vascular procedures during the same surgical session (stenting and/or&#xD;
             endarterectomy of the same artery are allowed).&#xD;
&#xD;
          -  Have an infection in the anatomic surgical area.&#xD;
&#xD;
          -  Have a history of severe (e.g. anaphylactic) reactions to blood or to any&#xD;
             blood-derived product.&#xD;
&#xD;
          -  Have previous known sensitivity to any Fibrin Sealant Grifols, heparin, or protamine&#xD;
             component.&#xD;
&#xD;
          -  Females who are pregnant or nursing a child at Baseline (within 24 hours prior to&#xD;
             surgical procedure).&#xD;
&#xD;
          -  Have undergone a therapeutic surgical procedure within 30 days from the screening&#xD;
             visit.&#xD;
&#xD;
          -  Target bleeding site cannot be identified.&#xD;
&#xD;
          -  Target bleeding site has mild or severe arterial bleeding.&#xD;
&#xD;
          -  Occurrence of major intraoperative complications that require resuscitation or&#xD;
             deviation from the planned surgical procedure.&#xD;
&#xD;
          -  Intraoperative change in planned surgical procedure, which results in subject no&#xD;
             longer meeting preoperative inclusion and/or exclusion criteria.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>407</name>
      <address>
        <city>Florence</city>
        <state>Alabama</state>
        <zip>35630</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>125</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>119</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>149</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>148</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>137</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>140</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>114</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>110</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>146</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>132</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>129</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>135</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>102</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>142</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467-2401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>406</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>113</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>409</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>104</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>100, 128</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>115</name>
      <address>
        <city>West Reading</city>
        <state>Pennsylvania</state>
        <zip>19611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>147</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>402</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>139</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132-3201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>103</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>138</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>111</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>501</name>
      <address>
        <city>Miskolc</city>
        <zip>03526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>500</name>
      <address>
        <city>Pecs</city>
        <zip>07623</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>502</name>
      <address>
        <city>Veszprém</city>
        <zip>8200</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>540</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630055</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>542</name>
      <address>
        <city>Rostov-on-Don</city>
        <zip>344022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>541</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>194354</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>543</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>195271</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>544</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197374</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>523</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>521</name>
      <address>
        <city>Belgrade</city>
        <zip>11040</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>522,524</name>
      <address>
        <city>Novi Sad</city>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <results_first_submitted>December 16, 2016</results_first_submitted>
  <results_first_submitted_qc>February 21, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 6, 2017</results_first_posted>
  <last_update_submitted>February 21, 2017</last_update_submitted>
  <last_update_submitted_qc>February 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vascular Surgery</keyword>
  <keyword>Fibrin Sealant</keyword>
  <keyword>Polytetrafluoroethylene (PTFE) grafts</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrin Tissue Adhesive</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Fibrin Sealant Grifols</title>
          <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
        </group>
        <group group_id="P2">
          <title>Manual Compression</title>
          <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part I + Part II (Overall Study)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="168"/>
                <participants group_id="P2" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Study up to Week 6</title>
              <participants_list>
                <participants group_id="P1" count="164"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="152">Completed Virology follow-up visit at Month 3 or Month 6</participants>
                <participants group_id="P2" count="55">Completed Virology follow-up visit at Month 3 or Month 6</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Primary Part II</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="109"/>
                <participants group_id="P2" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Study up to Week 6</title>
              <participants_list>
                <participants group_id="P1" count="106"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="99">Completed Virology follow-up visit at Month 3 or Month 6</participants>
                <participants group_id="P2" count="55">Completed Virology follow-up visit at Month 3 or Month 6</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Fibrin Sealant Grifols</title>
          <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
        </group>
        <group group_id="B2">
          <title>Manual Compression</title>
          <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</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="168"/>
            <count group_id="B2" value="57"/>
            <count group_id="B3" value="225"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="63.65" spread="9.036"/>
                    <measurement group_id="B2" value="62.04" spread="10.734"/>
                    <measurement group_id="B3" value="63.24" spread="9.496"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Between 18 and 64 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="90"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="103"/>
                  </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="51"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="117"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="148"/>
                  </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>Russian Federation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hungary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serbia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start</title>
        <description>Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.</description>
        <time_frame>From start of treatment until 4 minutes after treatment start</time_frame>
        <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Fibrin Sealant Grifols</title>
            <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
          </group>
          <group group_id="O2">
            <title>Manual Compression</title>
            <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start</title>
          <description>Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.</description>
          <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
          <units>Percent of subjects achieving hemostasis</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.1"/>
                    <measurement group_id="O2" value="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Hemostasis (TTH)</title>
        <description>Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start.&#xD;
In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated.&#xD;
All calculations were performed using SAS PROC LIFETEST</description>
        <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
        <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Fibrin Sealant Grifols</title>
            <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
          </group>
          <group group_id="O2">
            <title>Manual Compression</title>
            <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Hemostasis (TTH)</title>
          <description>Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start.&#xD;
In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated.&#xD;
All calculations were performed using SAS PROC LIFETEST</description>
          <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
          <units>minutes</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" lower_limit="NA" upper_limit="NA">Neither the lower nor upper 95% CI limit for median TTH could be estimated; for all time points with hemostatic assessment, none of the 95% CIs of the S(t) contained 0.5 (corresponding to the 50th percentile, ie, median). See Measure Description.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="10.00" upper_limit="NA">Median TTH could not be estimated precisely; most subjects did not achieve hemostasis by 10 minutes after start of treatment and were considered censored. Lower limit of the 95% CI was 10 minutes, it was deduced that the median TTH was ≥10 minutes.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points</title>
        <description>Cumulative proportion of subjects having achieved hemostasis by each of the following time points:&#xD;
At 5 minutes following start of study treatment&#xD;
At 7 minutes following start of study treatment&#xD;
At 10 minutes following start of study treatment</description>
        <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
        <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Fibrin Sealant Grifols</title>
            <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
          </group>
          <group group_id="O2">
            <title>Manual Compression</title>
            <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points</title>
          <description>Cumulative proportion of subjects having achieved hemostasis by each of the following time points:&#xD;
At 5 minutes following start of study treatment&#xD;
At 7 minutes following start of study treatment&#xD;
At 10 minutes following start of study treatment</description>
          <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
          <units>Percent of subjects achieving hemostasis</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hemostasis by 5 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.7"/>
                    <measurement group_id="O2" value="28.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemostasis by 7 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.4"/>
                    <measurement group_id="O2" value="35.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemostasis by 10 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.1"/>
                    <measurement group_id="O2" value="45.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Prevalence of Treatment Failures</title>
        <description>Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.</description>
        <time_frame>From start of treatment until 10 minutes after treatment start</time_frame>
        <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Fibrin Sealant Grifols</title>
            <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
          </group>
          <group group_id="O2">
            <title>Manual Compression</title>
            <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
          </group>
        </group_list>
        <measure>
          <title>Prevalence of Treatment Failures</title>
          <description>Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.</description>
          <population>Efficacy analysis was performed on subjects in the Primary Part (II) of the study</population>
          <units>percent of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.9"/>
                    <measurement group_id="O2" value="77.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from the time informed consent was obtained through the Post-Operative Week 6 (±4 days) Visit</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Fibrin Sealant Grifols</title>
          <description>Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total), applied topically to target bleeding site.</description>
        </group>
        <group group_id="E2">
          <title>Manual Compression</title>
          <description>Direct manual compression of target bleeding site with gauze/laparotomy pads.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic gastroparesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Gangrene</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Graft infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arteriovenous fistula thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Reocclusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Vascular graft occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Vascular graft thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Vascular pseudoaneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Parvovirus B19 test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lung neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid sinus syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Cerebral haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Lymphorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="132" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anaemia postoperative</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="57"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Body temperature increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="57"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="168"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="57"/>
              </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>Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Henry Li, PhD</name_or_title>
      <organization>Grifols Therapeutics Inc</organization>
      <phone>+1 919 316 6042</phone>
      <email>henry.li@grifols.com</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/NCT01662856
org study id: IG1101
nct id: NCT01662856
lead sponsor: 
The purpose of this study is to demonstrate that the application of Fibrin Sealant Grifols
      provides a measurable benefit when compared to hemostasis achieved through conventional
      surgical technique (suture) and by standard hemostatic action, such as mechanical pressure
      through manual compression. This study has a Preliminary Part (I) in which all subjects are
      treated with Fibrin Sealant Grifols and a Primary Part (II) in which subjects are randomized
      in a 2:1 ratio to either Fibrin Sealant Grifols or manual compression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
measure: Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start
time frame: From start of treatment until 4 minutes after treatment start
description: Subjects achieving hemostasis at the target bleeding site by 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.
measure: Time to Hemostasis (TTH)
time frame: From start of treatment until 10 minutes after treatment start
description: Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start.
In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated.
All calculations were performed using SAS PROC LIFETEST
measure: Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points
time frame: From start of treatment until 10 minutes after treatment start
description: Cumulative proportion of subjects having achieved hemostasis by each of the following time points:
At 5 minutes following start of study treatment
At 7 minutes following start of study treatment
At 10 minutes following start of study treatment
measure: Prevalence of Treatment Failures
time frame: From start of treatment until 10 minutes after treatment start
description: Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.
arm group label: Fibrin Sealant Grifols
arm group type: Experimental
description: Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).
arm group label: Manual Compression
arm group type: Active Comparator
description: Direct manual compression of target bleeding site with gauze/laparotomy pads.
intervention type: Biological
intervention name: Fibrin Sealant Grifols
description: Combination of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).
arm group label: Fibrin Sealant Grifols
intervention type: Procedure
intervention name: Manual Compression
description: Direct manual compression of target bleeding site with gauze/laparotomy pads.
arm group label: Manual Compression
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Hungary
country: Russian Federation
country: Serbia
country: United States
responsible party type: Sponsor
mesh term: Fibrin Tissue Adhesive
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 