<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/NCT04459871</url>
  </required_header>
  <id_info>
    <org_study_id>ZGrhT002</org_study_id>
    <nct_id>NCT04459871</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Topical Recombinant Human Thrombin(rhThrombin) for Surgical Hemostasis</brief_title>
  <official_title>A Phase 3, Stratified Randomized, Double-blind, Placebo-controlled Study of Topical Recombinant Human Thrombin (rhThrombin) in Surgical Hemostasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A multicenter, stratified randomized, double-blind, placebo-controlled, phase 3 clinical&#xD;
      trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After establishing eligibility, subjects will be randomized in a 2:1 ratio to receive&#xD;
      rhThrombin (1000 U/mL) or placebo. During a surgical procedure, study participants will be&#xD;
      treated with blinded study drug (rhThrombin or placebo) in combination with an absorbable&#xD;
      gelatin sponge at appropriate bleeding evaluation site(s). 510 patients will participate in&#xD;
      the study.&#xD;
&#xD;
      In this study, stratified random enrollment was conducted according to the&#xD;
      condition(experimental group or control group) of the subjects.Stratification factors were&#xD;
      centered, gender (male/female) and age (18 ≤ age &lt;60/60 ≤ age ≤70).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 11, 2019</start_date>
  <completion_date type="Actual">October 20, 2021</completion_date>
  <primary_completion_date type="Actual">October 20, 2021</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>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The rate of complete hemostasis within 6 minutes.</measure>
    <time_frame>6 minutes</time_frame>
    <description>Those who did not stop bleeding within 6 minutes were defined as treatment failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events(AE)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Hemostasis(TTH)</measure>
    <time_frame>Evaluate the effect of hemostasis every 30sec until hemostasis is completed or 6 minutes of observation is completed</time_frame>
    <description>TTH will be assessed for up to 6 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>At baseline and Day 29</time_frame>
    <description>Positive rate of anti-recombinant human thrombin neutralizing antibody.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">348</enrollment>
  <condition>Surgical Hemostasis</condition>
  <arm_group>
    <arm_group_label>The experimental group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The topical recombinant human thrombin(rhThrombin) was prepared into 1000IU/mL solution with 10ml normal saline and used in combination with absorbable gelatin spongeat at appropriate bleeding evaluation site(s).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>The control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo was prepared into a solution with 10mL normal saline and used in combination with absorbable gelatin sponge at appropriate bleeding evaluation site(s).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>recombinant human Thrombin(CHO cell)</intervention_name>
    <description>2 rhThrombin, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).</description>
    <arm_group_label>The experimental group</arm_group_label>
    <other_name>rhThrombin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).</description>
    <arm_group_label>The control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 to 70 years old (including 18 and 70 years old), male or female;&#xD;
&#xD;
          -  Patients with wedge-shaped liver resection or anatomical liver resection(1-5&#xD;
             consecutive liver segments);&#xD;
&#xD;
          -  After the operation was controlled by standard surgical hemostasis, there were still&#xD;
             patients with mild/moderate bleeding lesions (bleeding, non-arterial bleeding);&#xD;
&#xD;
          -  Electrolytes (K, Na, CL, Ca, P, Mg) and ECG are normal or abnormal, Investigators&#xD;
             believe that patients who do not affect surgery&#xD;
&#xD;
          -  No other therapeutic surgery within 4 weeks before enrollment;&#xD;
&#xD;
          -  Patients who have not used blood products within 24 hours before surgery;&#xD;
&#xD;
          -  In compliance with the requirements of the ethics committee, patients voluntarily&#xD;
             signed informed consent and were able to conduct visits as required by the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known diseases of the blood system, including patients with coagulopathy or bleeding&#xD;
             tendency;&#xD;
&#xD;
          -  Patients with unstable vital signs for more than 24 hours;&#xD;
&#xD;
          -  A history of severe heart, brain, and vascular disease within 6 months, including&#xD;
             patients with a history of TIA, non-disabling cerebral infarction, myocardial&#xD;
             infarction, unstable angina, or intracranial hemorrhage;&#xD;
&#xD;
          -  Active bleeding or abnormal coagulation function (PT&gt;16s, APTT&gt;43s, INR≥2) or&#xD;
             receiving thrombolysis, anticoagulation or antiplatelet therapy;&#xD;
&#xD;
          -  Have used drugs that affect the function of the coagulation system within 1 week&#xD;
             before surgery (including but not limited to: aspirin, clopidogrel, ticlopidine,&#xD;
             fensulfamide, desmopressin, aminotoluic acid, dipyridamole, ginkgo Leaf preparations,&#xD;
             heparin, warfarin, citrate, hemagglutinin, Vk, anti-fibrotic solvents, hemostatic, Vc,&#xD;
             etc.);&#xD;
&#xD;
          -  Women during pregnancy and lactation;&#xD;
&#xD;
          -  Participants who participated in clinical trials of other drugs within 4 weeks before&#xD;
             enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheng Yan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zhejiang University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hepatic resection</keyword>
  <keyword>rhThrombin,topical</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04459871
org study id: ZGrhT002
nct id: NCT04459871
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A multicenter, stratified randomized, double-blind, placebo-controlled, phase 3 clinical
      trial.
After establishing eligibility, subjects will be randomized in a 2:1 ratio to receive
      rhThrombin (1000 U/mL) or placebo. During a surgical procedure, study participants will be
      treated with blinded study drug (rhThrombin or placebo) in combination with an absorbable
      gelatin sponge at appropriate bleeding evaluation site(s). 510 patients will participate in
      the study.

      In this study, stratified random enrollment was conducted according to the
      condition(experimental group or control group) of the subjects.Stratification factors were
      centered, gender (male/female) and age (18 ≤ age <60/60 ≤ age ≤70).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: The rate of complete hemostasis within 6 minutes.
time frame: 6 minutes
description: Those who did not stop bleeding within 6 minutes were defined as treatment failure.
measure: Incidence of adverse events(AE)
time frame: Up to 28 days
description: An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment.
measure: Time to Hemostasis(TTH)
time frame: Evaluate the effect of hemostasis every 30sec until hemostasis is completed or 6 minutes of observation is completed
description: TTH will be assessed for up to 6 minutes
measure: Immunogenicity
time frame: At baseline and Day 29
description: Positive rate of anti-recombinant human thrombin neutralizing antibody.
arm group label: The experimental group
arm group type: Experimental
description: The topical recombinant human thrombin(rhThrombin) was prepared into 1000IU/mL solution with 10ml normal saline and used in combination with absorbable gelatin spongeat at appropriate bleeding evaluation site(s).
arm group label: The control group
arm group type: Placebo Comparator
description: The placebo was prepared into a solution with 10mL normal saline and used in combination with absorbable gelatin sponge at appropriate bleeding evaluation site(s).
intervention type: Biological
intervention name: recombinant human Thrombin(CHO cell)
description: 2 rhThrombin, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).
arm group label: The experimental group
other name: rhThrombin
intervention type: Biological
intervention name: placebo
description: placebo, dissolved in 5mL sterile saline and mixed, the final solution contains 1000IU/mL rhThrombin solution (clear and transparent liquid).
arm group label: The control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Sheng Yan, PhD
role: Principal Investigator
affiliation: Zhejiang University
facility: 
country: China
responsible party type: Sponsor
mesh term: Thrombin