<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/NCT03251547</url>
  </required_header>
  <id_info>
    <org_study_id>SEChong</org_study_id>
    <nct_id>NCT03251547</nct_id>
  </id_info>
  <brief_title>Recombinant Activated Factor VII in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia</brief_title>
  <official_title>Recombinant Activated Factor VII (rFVIIa/ NovoSeven®) in the Management of Massive Bleeding in Hospital Universiti Sains Malaysia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universiti Sains Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universiti Sains Malaysia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a retrospective descriptive study, to study the treatment indications, changes in&#xD;
      transfusion need, coagulation profiles changes and clinical outcome (survival, complication)&#xD;
      of non-haemophiliac patients who received activated factor seven (rFVIIa / NovoSeven®) during&#xD;
      massive bleeding in Hospital Universiti Sains Malaysia (HUSM)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Effective hemostasis can be life-saving. However, there is still lack of an ideal hemostatic&#xD;
      drug which is safe and effective.&#xD;
&#xD;
      Recombinant activated factor VII (rFVIIa; Novo Nordisk, Bagsvaerd, Denmark) is a hemostatic&#xD;
      agent originally developed for the management of bleeding in haemophilia A and B patients&#xD;
      with inhibitors to factor VIII or IX respectively.&#xD;
&#xD;
      Recombinant FVIIa involves in extrinsic clotting pathway where it forms a complex with tissue&#xD;
      factor which in the presence of calcium and phospholipids activates coagulation factor X&#xD;
      which then initiates the conversion of prothrombin into thrombin at the site of injury&#xD;
      (Figure 1). Formation of thrombin and clot stabilises platelet plug and form a tight fibrin&#xD;
      structure which is resistant to lysis. Due to the efficient haemostatic property but the&#xD;
      unknown safety profile, it is only being used as one of the last resorts during massive&#xD;
      intractable bleeding episode among the non-haemophilia patients.&#xD;
&#xD;
      Efficacy and safety profile is the most important concern of a haemostatic drug like rFVIIa.&#xD;
      However, there is ongoing controversial evidence regarding thromboembolic complications and&#xD;
      survival benefit of the off-label use of rFVIIa in massive bleeding (Patel et al2012).&#xD;
&#xD;
      This a study to learn about the previous usage, outcome and complications of rFVIIa use in&#xD;
      massive intractable bleeding management in a single centre (Hospital University Sains&#xD;
      Malaysia / HUSM) in Malaysia.&#xD;
&#xD;
      The data of patients who had undergone massive bleeding will be available from pharmacy&#xD;
      department and recruited from medical record department of HUSM.&#xD;
&#xD;
      These include:&#xD;
&#xD;
        1. Underlying condition, BMI of patient.&#xD;
&#xD;
        2. Indication for blood transfusion.&#xD;
&#xD;
        3. Dose of rFVIIa.&#xD;
&#xD;
        4. Other medication (vitamin K, tranexamic acid, anticoagulant, antiplatelet) given to&#xD;
           patient.&#xD;
&#xD;
        5. Blood pressure, haemoglobin level, coagulation profile, and blood product requirements&#xD;
           24 hours before and after administration of rFVIIa.&#xD;
&#xD;
        6. Survival at 24-hour and day-30 post administration of rFVIIa were also recorded.&#xD;
&#xD;
        7. Thromboembolism complication post administration of rFVIIa.&#xD;
&#xD;
        8. Duration of stay.&#xD;
&#xD;
      Patients' identities will be anonymized without disclosure of personal identifiable&#xD;
      information to third-party organizations.&#xD;
&#xD;
      Statistical calculations will be done using SPSS (Statistical Package for the Social Science)&#xD;
      software.&#xD;
&#xD;
      Quantitative data will be expressed as mean ± standard deviation (SD) and median&#xD;
      (interquartile range,IQR). For comparison before and after of administration of rFVIIa, data&#xD;
      will be analyzed using paired t- test if the data is normally distributed. For skewed data,&#xD;
      Wilcoxon Signed-Rank test will be used for analysis. The differences willl be considered&#xD;
      significant at a p &lt; 0.05.&#xD;
&#xD;
      For the outcome of survival and thromboembolic complication, data will be analyzed&#xD;
      descriptively with frequency and percentage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 21, 2017</start_date>
  <completion_date type="Actual">November 15, 2017</completion_date>
  <primary_completion_date type="Actual">October 15, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in blood transfusion requirement</measure>
    <time_frame>24 hour before and after administration of rFVIIa</time_frame>
    <description>To study the changes in blood product requirement in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival rate</measure>
    <time_frame>30 days</time_frame>
    <description>To describe the outcome of survival at 24-hour and Day-30 after receiving rFVIIa</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in coagulation profile</measure>
    <time_frame>24 hour before and after administration of rFVIIa</time_frame>
    <description>To study the changes in coagulation profile in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Complication rate</measure>
    <time_frame>30 days</time_frame>
    <description>To describe the outcome of complication of non-hemophiliac patient after receiving rFVIIa</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">76</enrollment>
  <condition>Massive Hemorrhage</condition>
  <condition>Massive Blood Loss</condition>
  <condition>Massive Blood Transfusion; Thrombocytopenia</condition>
  <arm_group>
    <arm_group_label>NovoSeven</arm_group_label>
    <description>Non-hemophiliac patients experienced massive haemorrhage who was treated with recombinant activated factor VII</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NovoSeven</intervention_name>
    <description>To survey retrospectively the treatment indications, clinical outcome, transfusion need and changes in coagulation profiles of non-haemophiliac patients who had received rFVIIa during massive bleeding</description>
    <arm_group_label>NovoSeven</arm_group_label>
    <other_name>recombinant activated factor VII</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Non-haemophilic patients who had received rFVIIa during massive bleeding in Hospital&#xD;
        Universiti Sains Malaysia (HUSM)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patient with massive bleeding who had received rFVIIa from year 2006 to year 2016.&#xD;
&#xD;
          -  Massive bleeding criteria&#xD;
&#xD;
               -  Loss of one blood volume within a 24 hour&#xD;
&#xD;
               -  50% blood volume loss within 3 h&#xD;
&#xD;
               -  Rate of loss of 150 ml/min&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Haemophilia patient who received rFVIIa&#xD;
&#xD;
          -  Poor documentation / record unavailable in HUSM&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chong Soon Eu, MD, MMed</last_name>
    <role>Study Chair</role>
    <affiliation>Universiti Sains Malaysia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nurfatin Mohd Shah, BSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universiti Sains Malaysia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universiti Sains Malaysia</name>
      <address>
        <city>Kota Bharu</city>
        <state>Kelantan</state>
        <zip>16150</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <reference>
    <citation>Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014 Feb 27;370(9):847-59. doi: 10.1056/NEJMra1208626. No abstract available.</citation>
    <PMID>24571757</PMID>
  </reference>
  <reference>
    <citation>Bougle A, Harrois A, Duranteau J. Resuscitative strategies in traumatic hemorrhagic shock. Ann Intensive Care. 2013 Jan 12;3(1):1. doi: 10.1186/2110-5820-3-1.</citation>
    <PMID>23311726</PMID>
  </reference>
  <reference>
    <citation>Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997 May;42(5):857-61; discussion 861-2. doi: 10.1097/00005373-199705000-00016.</citation>
    <PMID>9191667</PMID>
  </reference>
  <reference>
    <citation>Faraoni D, Van Der Linden P. A systematic review of antifibrinolytics and massive injury. Minerva Anestesiol. 2014 Oct;80(10):1115-22. Epub 2013 Nov 28.</citation>
    <PMID>24287671</PMID>
  </reference>
  <reference>
    <citation>Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol. 2007 Aug;82(8):731-5. doi: 10.1002/ajh.20940.</citation>
    <PMID>17492648</PMID>
  </reference>
  <reference>
    <citation>Kobayashi T, Nakabayashi M, Yoshioka A, Maeda M, Ikenoue T. Recombinant activated factor VII (rFVIIa/NovoSeven(R)) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan. Int J Hematol. 2012 Jan;95(1):57-63. doi: 10.1007/s12185-011-0974-9. Epub 2011 Dec 9.</citation>
    <PMID>22160834</PMID>
  </reference>
  <reference>
    <citation>Lin Y, Moltzan CJ, Anderson DR; National Advisory Committee on Blood and Blood Products. The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework. Transfus Med. 2012 Dec;22(6):383-94. doi: 10.1111/j.1365-3148.2012.01164.x. Epub 2012 May 27.</citation>
    <PMID>22630348</PMID>
  </reference>
  <reference>
    <citation>Logan AC, Goodnough LT. Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010;2010:153-9. doi: 10.1182/asheducation-2010.1.153.</citation>
    <PMID>21239786</PMID>
  </reference>
  <reference>
    <citation>Palmason R, Vidarsson B, Sigvaldason K, Ingimarsson JP, Gudbjartsson T, Sigurdsson GH, Onundarson PT. Recombinant factor VIIa as last-resort treatment of desperate haemorrhage. Acta Anaesthesiol Scand. 2012 May;56(5):636-44. doi: 10.1111/j.1399-6576.2012.02688.x.</citation>
    <PMID>22489992</PMID>
  </reference>
  <reference>
    <citation>Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013 Apr 19;17(2):R76. doi: 10.1186/cc12685.</citation>
    <PMID>23601765</PMID>
  </reference>
  <reference>
    <citation>Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth. 2000 Sep;85(3):487-91. doi: 10.1093/bja/85.3.487.</citation>
    <PMID>11103199</PMID>
  </reference>
  <reference>
    <citation>Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, Sundaram V, McMahon D, Olkin I, McDonald KM, Owens DK, Stafford RS. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011 Apr 19;154(8):529-40. doi: 10.7326/0003-4819-154-8-201104190-00004.</citation>
    <PMID>21502651</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>October 9, 2018</last_update_submitted>
  <last_update_submitted_qc>October 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universiti Sains Malaysia</investigator_affiliation>
    <investigator_full_name>Soon Eu Chong</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>rFVIIa</keyword>
  <keyword>Massive Hemorrhage</keyword>
  <keyword>non-hemophilia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03251547
org study id: SEChong
nct id: NCT03251547
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a retrospective descriptive study, to study the treatment indications, changes in
      transfusion need, coagulation profiles changes and clinical outcome (survival, complication)
      of non-haemophiliac patients who received activated factor seven (rFVIIa / NovoSeven®) during
      massive bleeding in Hospital Universiti Sains Malaysia (HUSM)
Effective hemostasis can be life-saving. However, there is still lack of an ideal hemostatic
      drug which is safe and effective.

      Recombinant activated factor VII (rFVIIa; Novo Nordisk, Bagsvaerd, Denmark) is a hemostatic
      agent originally developed for the management of bleeding in haemophilia A and B patients
      with inhibitors to factor VIII or IX respectively.

      Recombinant FVIIa involves in extrinsic clotting pathway where it forms a complex with tissue
      factor which in the presence of calcium and phospholipids activates coagulation factor X
      which then initiates the conversion of prothrombin into thrombin at the site of injury
      (Figure 1). Formation of thrombin and clot stabilises platelet plug and form a tight fibrin
      structure which is resistant to lysis. Due to the efficient haemostatic property but the
      unknown safety profile, it is only being used as one of the last resorts during massive
      intractable bleeding episode among the non-haemophilia patients.

      Efficacy and safety profile is the most important concern of a haemostatic drug like rFVIIa.
      However, there is ongoing controversial evidence regarding thromboembolic complications and
      survival benefit of the off-label use of rFVIIa in massive bleeding (Patel et al2012).

      This a study to learn about the previous usage, outcome and complications of rFVIIa use in
      massive intractable bleeding management in a single centre (Hospital University Sains
      Malaysia / HUSM) in Malaysia.

      The data of patients who had undergone massive bleeding will be available from pharmacy
      department and recruited from medical record department of HUSM.

      These include:

        1. Underlying condition, BMI of patient.

        2. Indication for blood transfusion.

        3. Dose of rFVIIa.

        4. Other medication (vitamin K, tranexamic acid, anticoagulant, antiplatelet) given to
           patient.

        5. Blood pressure, haemoglobin level, coagulation profile, and blood product requirements
           24 hours before and after administration of rFVIIa.

        6. Survival at 24-hour and day-30 post administration of rFVIIa were also recorded.

        7. Thromboembolism complication post administration of rFVIIa.

        8. Duration of stay.

      Patients' identities will be anonymized without disclosure of personal identifiable
      information to third-party organizations.

      Statistical calculations will be done using SPSS (Statistical Package for the Social Science)
      software.

      Quantitative data will be expressed as mean ± standard deviation (SD) and median
      (interquartile range,IQR). For comparison before and after of administration of rFVIIa, data
      will be analyzed using paired t- test if the data is normally distributed. For skewed data,
      Wilcoxon Signed-Rank test will be used for analysis. The differences willl be considered
      significant at a p < 0.05.

      For the outcome of survival and thromboembolic complication, data will be analyzed
      descriptively with frequency and percentage.
observational model: Cohort
time perspective: Retrospective
measure: Changes in blood transfusion requirement
time frame: 24 hour before and after administration of rFVIIa
description: To study the changes in blood product requirement in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it.
measure: Survival rate
time frame: 30 days
description: To describe the outcome of survival at 24-hour and Day-30 after receiving rFVIIa
measure: Changes in coagulation profile
time frame: 24 hour before and after administration of rFVIIa
description: To study the changes in coagulation profile in 24 hours before and after administration of rFVIIa in massive bleeding patient in HUSM and to describe the factors affecting it
measure: Complication rate
time frame: 30 days
description: To describe the outcome of complication of non-hemophiliac patient after receiving rFVIIa
arm group label: NovoSeven
description: Non-hemophiliac patients experienced massive haemorrhage who was treated with recombinant activated factor VII
intervention type: Drug
intervention name: NovoSeven
description: To survey retrospectively the treatment indications, clinical outcome, transfusion need and changes in coagulation profiles of non-haemophiliac patients who had received rFVIIa during massive bleeding
arm group label: NovoSeven
other name: recombinant activated factor VII
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Chong Soon Eu, MD, MMed
role: Study Chair
affiliation: Universiti Sains Malaysia
last name: Nurfatin Mohd Shah, BSc
role: Principal Investigator
affiliation: Universiti Sains Malaysia
facility: 
country: Malaysia
citation: Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014 Feb 27;370(9):847-59. doi: 10.1056/NEJMra1208626. No abstract available.
PMID: 24571757
citation: Bougle A, Harrois A, Duranteau J. Resuscitative strategies in traumatic hemorrhagic shock. Ann Intensive Care. 2013 Jan 12;3(1):1. doi: 10.1186/2110-5820-3-1.
PMID: 23311726
citation: Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997 May;42(5):857-61; discussion 861-2. doi: 10.1097/00005373-199705000-00016.
PMID: 9191667
citation: Faraoni D, Van Der Linden P. A systematic review of antifibrinolytics and massive injury. Minerva Anestesiol. 2014 Oct;80(10):1115-22. Epub 2013 Nov 28.
PMID: 24287671
citation: Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol. 2007 Aug;82(8):731-5. doi: 10.1002/ajh.20940.
PMID: 17492648
citation: Kobayashi T, Nakabayashi M, Yoshioka A, Maeda M, Ikenoue T. Recombinant activated factor VII (rFVIIa/NovoSeven(R)) in the management of severe postpartum haemorrhage: initial report of a multicentre case series in Japan. Int J Hematol. 2012 Jan;95(1):57-63. doi: 10.1007/s12185-011-0974-9. Epub 2011 Dec 9.
PMID: 22160834
citation: Lin Y, Moltzan CJ, Anderson DR; National Advisory Committee on Blood and Blood Products. The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework. Transfus Med. 2012 Dec;22(6):383-94. doi: 10.1111/j.1365-3148.2012.01164.x. Epub 2012 May 27.
PMID: 22630348
citation: Logan AC, Goodnough LT. Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010;2010:153-9. doi: 10.1182/asheducation-2010.1.153.
PMID: 21239786
citation: Palmason R, Vidarsson B, Sigvaldason K, Ingimarsson JP, Gudbjartsson T, Sigurdsson GH, Onundarson PT. Recombinant factor VIIa as last-resort treatment of desperate haemorrhage. Acta Anaesthesiol Scand. 2012 May;56(5):636-44. doi: 10.1111/j.1399-6576.2012.02688.x.
PMID: 22489992
citation: Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013 Apr 19;17(2):R76. doi: 10.1186/cc12685.
PMID: 23601765
citation: Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth. 2000 Sep;85(3):487-91. doi: 10.1093/bja/85.3.487.
PMID: 11103199
citation: Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, Sundaram V, McMahon D, Olkin I, McDonald KM, Owens DK, Stafford RS. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011 Apr 19;154(8):529-40. doi: 10.7326/0003-4819-154-8-201104190-00004.
PMID: 21502651
responsible party type: Principal Investigator
investigator affiliation: Universiti Sains Malaysia
investigator full name: Soon Eu Chong
investigator title: Dr
mesh term: Thrombocytopenia
mesh term: Hemorrhage
sharing ipd: Undecided