<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/NCT03752606</url>
  </required_header>
  <id_info>
    <org_study_id>022018</org_study_id>
    <nct_id>NCT03752606</nct_id>
  </id_info>
  <brief_title>Application of Tachosil During Lymphadenectomy</brief_title>
  <official_title>Does Intraoperative Application of TachoSil Reduce the Number of Lymphocele After Pelvic Lymphadenectomy?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Lublin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Lublin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevention of lymphoceles was assessed using collagen patch coated with the human&#xD;
      coagulation factors (TachoSil, Nycomed International Management GmbH, Zurich, Switzerland;&#xD;
      NCT Number ICMJE NCT01192022; Other Study ID Numbers ICMJE TC-2402-040-SP; U1111-1130-9121&#xD;
      Registry Identifier: WHO) on 50 consecutive patients with endometrial and cervical cancer&#xD;
      stages IB to II who had undergone open hysterectomy and pelvic lymphadenectomy (PL).&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Each patient was simultaneously randomized in two groups: as a control (side without Tachosil&#xD;
      applied) and study group (side with Tachosil applied). All surgical parameters were collected&#xD;
      and patients underwent ultrasound examination on postoperative days 1, 6, and 30, and at the&#xD;
      end of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was approved by the Bioethics Committee of the Medical University of Lublin,&#xD;
      Lublin, Poland (KE-0254/276/2013). The study population consisted of 50 women undergoing&#xD;
      pelvic lymphadenectomy for cervical and endometrial cancer and meeting the&#xD;
      inclusion/exclusion criteria requirements. Inclusion criteria for the study included women&#xD;
      undergoing open hysterectomy and lymphadenectomy for cervical or endometrial cancer, age&#xD;
      between 18 and 70 years, who signed a written informed consent. Exclusion criteria included&#xD;
      women with previously diagnosed lymph edema or disease of the lymphatic system or a known&#xD;
      disease of the immune system. Prospective randomized clinical intervention trial of 50 open&#xD;
      surgery during 2013-2014 at 2nd Department of Gynecology in Lublin. Women were centrally&#xD;
      randomized by the principal investigator (TR). Surgeons allocated Tachosil for one side (left&#xD;
      or right) after lymphadenectomy, second side was as a control side without Tachosil.&#xD;
      Allocation was communicated by telephone after informed consent had been obtained and after&#xD;
      lymphadenectomy had been completed. Outcome assessment was performed by the independent&#xD;
      reviewers. Outcome assessors were blinded to the treatment allocation. The open surgery were&#xD;
      performed as follows: in women who underwent routine pelvic lymphadenectomy, lymph node&#xD;
      tissue was removed from the external iliac vessels, the obturator fossa, the interiliac&#xD;
      region, and the common iliac region after identification and appropriate preparation of iliac&#xD;
      vessels and obturator nerve. At the end of the procedure, hemostasis was checked. A Tachosil®&#xD;
      patch of 4.8x4.8 cm was attached to one side of the obturator fossa (study group) and the&#xD;
      same patient constituted also control group, because no Tachosil® patch was used on the&#xD;
      second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed.&#xD;
      Patients had to agree to participate in the study and signed informed consent at least one&#xD;
      day before surgery. Taking into consideration the examined group the patient was allocated&#xD;
      to, the surgeon applied either one Tachosil® patches in the study group or no Tachosil® in&#xD;
      the control group. After placing for 4 minutes, a uniform pressure was applied to it to&#xD;
      provide rapid haemostasis by forming a strong, fibrin clot adjacent to the tissue surface.&#xD;
      Tachosil was placed alternately once in the left, once in the right obturator fossa, so that&#xD;
      each of the patients participating in the study could be their own control. The next step was&#xD;
      a radical hysterectomy with adnexa. After completion of the procedure, the stump of the&#xD;
      vagina stitching to the hollow was performed by passing the vaginal seam through the vaginal&#xD;
      wall, the right-side sacro-uterus ligament, the right round ligament, the peritoneal uterine&#xD;
      vesiculitis, the left round ligament, the left sacro-uterine ligament and finally the vaginal&#xD;
      wall. This way of fixation allowed free lymphatic drainage of the retroperitoneal space. Two&#xD;
      drains from the vicinity of the pits of the curtains were removed through the abdominal wall,&#xD;
      which were left to the second day after surgery or longer if the volume of secretion in the&#xD;
      drainage exceeded 40 ml per day. The urinary bladder catheter was removed on the third day&#xD;
      after surgery and ultrasound after voiding (PVR) was evaluated. Surgical procedures were&#xD;
      performed by four doctors with extensive experience in oncological gynecology. The surgical&#xD;
      protocols were blinded to other researchers who controlled patients in the postoperative&#xD;
      period. The data obtained by them were analyzed by an independent reviewer. The evaluation&#xD;
      criteria of the study were the development of lymph cysts and their volume. Antibiotic&#xD;
      prophylaxis was implemented according to local hospital recommendations. In addition,&#xD;
      metronidazole was administered at a dose of 500 mg every 8 hours. i.v. for the first three&#xD;
      days after the procedure. Patients also received small-molecule heparin at a dose of 4,000 IU&#xD;
      from the day preceding the surgery up to 30 days after its completion. Due to the fact that&#xD;
      lymphatic cysts usually appear 7 to 15 days after lymphadenectomy, the ultrasound examination&#xD;
      of the presence and volume of lymphocele was performed on the 7th and 30th day after the&#xD;
      surgery and after completing the oncological complementary treatmentThe criteria proposed by&#xD;
      Tinelli et al. were used to define lymphocele.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 29, 2013</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>A Tachosil® patch of 4.8x4.8 cm was attached to one side of the obturator fossa (study group) and the same patient constituted also control group, because no Tachosil® patch was used on the second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed. Patients had to agree to participate in the study and signed informed consent at least one day before surgery. Taking into consideration the examined group the patient was allocated to, the surgeon applied either one Tachosil® patches in the study group or no Tachosil® in the control group. After placing for 4 minutes, a uniform pressure was applied to it to provide rapid haemostasis by forming a strong, fibrin clot adjacent to the tissue surface. Tachosil was placed alternately once in the left, once in the right obturator fossa, so that each of the patients participating in the study could be their own control.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Allocation was communicated by telephone after informed consent had been obtained and after lymphadenectomy had been completed. Outcome assessment was performed by the independent reviewers. Outcome assessors were blinded to the treatment allocation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence and volume of lymphocele.</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants with lymphocele as assessed by USG scan at 1,6,30 days and the drainage volume in ml with/without Tachosil assessed by USG scan at 1,2,6,30 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of lymphocele after adjuvant treatment</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants with lymphocele as assessed by USG scan after complement adjuvant treatament</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Lymphocele</condition>
  <condition>Endometrial Cancer</condition>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>TACHOSIL GROUP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Surgical procedures were performed by four doctors with extensive experience in oncological gynecology. A TachoSil® absorbable patch of 4.8x4.8 cm was attached, once, intraoperatively to one side of the obturator fossa (study group). Specific drainage of the retroperitoneum was performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GROUP WITHOUT TACHOSIL</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The same patient constituted also control group, because no TachoSil® absorbable patche was used on the second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TACHOSIL GROUP</intervention_name>
    <arm_group_label>TACHOSIL GROUP</arm_group_label>
    <other_name>NCT01192022</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cervical cancer (FIGO IA1, IA2, IB1, IB2)&#xD;
&#xD;
          -  endometrial cancer (FIGO IA, IB, II)&#xD;
&#xD;
          -  age between 18 and 70 years&#xD;
&#xD;
          -  signed a written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  lymph edema&#xD;
&#xD;
          -  disease of the lymphatic system&#xD;
&#xD;
          -  a known disease of the immune system&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Women with cervical or endometrial cancer age between 18 and 70 years signed a written informed consent</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tomasz Rechberger, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>IInd Department of Gynecology, Medical University of Lublin, Poland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IInd Department of Gynecology</name>
      <address>
        <city>Lublin</city>
        <zip>20-954</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <results_reference>
    <citation>Tinelli A, Giorda G, Manca C, Pellegrino M, Prudenzano R, Guido M, Dell'Edera D, Malvasi A. Prevention of lymphocele in female pelvic lymphadenectomy by a collagen patch coated with the human coagulation factors: a pilot study. J Surg Oncol. 2012 Jun 15;105(8):835-40. doi: 10.1002/jso.22110. Epub 2011 Oct 10.</citation>
    <PMID>21987409</PMID>
  </results_reference>
  <results_reference>
    <citation>Tinelli A, Mynbaev OA, Tsin DA, Giorda G, Malvasi A, Guido M, Nezhat FR. Lymphocele prevention after pelvic laparoscopic lymphadenectomy by a collagen patch coated with human coagulation factors: a matched case-control study. Int J Gynecol Cancer. 2013 Jun;23(5):956-63. doi: 10.1097/IGC.0b013e31828eeea4.</citation>
    <PMID>23574881</PMID>
  </results_reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 18, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 26, 2018</study_first_posted>
  <last_update_submitted>November 21, 2018</last_update_submitted>
  <last_update_submitted_qc>November 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Lublin</investigator_affiliation>
    <investigator_full_name>Paweł Miotła</investigator_full_name>
    <investigator_title>Clinical Proffesor</investigator_title>
  </responsible_party>
  <keyword>lymphadenectomy</keyword>
  <keyword>lymphocele</keyword>
  <keyword>endometrial cancer</keyword>
  <keyword>cervical cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Lymphocele</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>from now to ongoing</ipd_time_frame>
    <ipd_access_criteria>from the corresponding author on reasonable request.</ipd_access_criteria>
  </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/NCT03752606
org study id: 022018
nct id: NCT03752606
lead sponsor: 
collaborator: 
has dmc: Yes
The prevention of lymphoceles was assessed using collagen patch coated with the human
      coagulation factors (TachoSil, Nycomed International Management GmbH, Zurich, Switzerland;
      NCT Number ICMJE NCT01192022; Other Study ID Numbers ICMJE TC-2402-040-SP; U1111-1130-9121
      Registry Identifier: WHO) on 50 consecutive patients with endometrial and cervical cancer
      stages IB to II who had undergone open hysterectomy and pelvic lymphadenectomy (PL).

      Methods:

      Each patient was simultaneously randomized in two groups: as a control (side without Tachosil
      applied) and study group (side with Tachosil applied). All surgical parameters were collected
      and patients underwent ultrasound examination on postoperative days 1, 6, and 30, and at the
      end of treatment.
The study was approved by the Bioethics Committee of the Medical University of Lublin,
      Lublin, Poland (KE-0254/276/2013). The study population consisted of 50 women undergoing
      pelvic lymphadenectomy for cervical and endometrial cancer and meeting the
      inclusion/exclusion criteria requirements. Inclusion criteria for the study included women
      undergoing open hysterectomy and lymphadenectomy for cervical or endometrial cancer, age
      between 18 and 70 years, who signed a written informed consent. Exclusion criteria included
      women with previously diagnosed lymph edema or disease of the lymphatic system or a known
      disease of the immune system. Prospective randomized clinical intervention trial of 50 open
      surgery during 2013-2014 at 2nd Department of Gynecology in Lublin. Women were centrally
      randomized by the principal investigator (TR). Surgeons allocated Tachosil for one side (left
      or right) after lymphadenectomy, second side was as a control side without Tachosil.
      Allocation was communicated by telephone after informed consent had been obtained and after
      lymphadenectomy had been completed. Outcome assessment was performed by the independent
      reviewers. Outcome assessors were blinded to the treatment allocation. The open surgery were
      performed as follows: in women who underwent routine pelvic lymphadenectomy, lymph node
      tissue was removed from the external iliac vessels, the obturator fossa, the interiliac
      region, and the common iliac region after identification and appropriate preparation of iliac
      vessels and obturator nerve. At the end of the procedure, hemostasis was checked. A Tachosil®
      patch of 4.8x4.8 cm was attached to one side of the obturator fossa (study group) and the
      same patient constituted also control group, because no Tachosil® patch was used on the
      second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed.
      Patients had to agree to participate in the study and signed informed consent at least one
      day before surgery. Taking into consideration the examined group the patient was allocated
      to, the surgeon applied either one Tachosil® patches in the study group or no Tachosil® in
      the control group. After placing for 4 minutes, a uniform pressure was applied to it to
      provide rapid haemostasis by forming a strong, fibrin clot adjacent to the tissue surface.
      Tachosil was placed alternately once in the left, once in the right obturator fossa, so that
      each of the patients participating in the study could be their own control. The next step was
      a radical hysterectomy with adnexa. After completion of the procedure, the stump of the
      vagina stitching to the hollow was performed by passing the vaginal seam through the vaginal
      wall, the right-side sacro-uterus ligament, the right round ligament, the peritoneal uterine
      vesiculitis, the left round ligament, the left sacro-uterine ligament and finally the vaginal
      wall. This way of fixation allowed free lymphatic drainage of the retroperitoneal space. Two
      drains from the vicinity of the pits of the curtains were removed through the abdominal wall,
      which were left to the second day after surgery or longer if the volume of secretion in the
      drainage exceeded 40 ml per day. The urinary bladder catheter was removed on the third day
      after surgery and ultrasound after voiding (PVR) was evaluated. Surgical procedures were
      performed by four doctors with extensive experience in oncological gynecology. The surgical
      protocols were blinded to other researchers who controlled patients in the postoperative
      period. The data obtained by them were analyzed by an independent reviewer. The evaluation
      criteria of the study were the development of lymph cysts and their volume. Antibiotic
      prophylaxis was implemented according to local hospital recommendations. In addition,
      metronidazole was administered at a dose of 500 mg every 8 hours. i.v. for the first three
      days after the procedure. Patients also received small-molecule heparin at a dose of 4,000 IU
      from the day preceding the surgery up to 30 days after its completion. Due to the fact that
      lymphatic cysts usually appear 7 to 15 days after lymphadenectomy, the ultrasound examination
      of the presence and volume of lymphocele was performed on the 7th and 30th day after the
      surgery and after completing the oncological complementary treatmentThe criteria proposed by
      Tinelli et al. were used to define lymphocele.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A Tachosil® patch of 4.8x4.8 cm was attached to one side of the obturator fossa (study group) and the same patient constituted also control group, because no Tachosil® patch was used on the second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed. Patients had to agree to participate in the study and signed informed consent at least one day before surgery. Taking into consideration the examined group the patient was allocated to, the surgeon applied either one Tachosil® patches in the study group or no Tachosil® in the control group. After placing for 4 minutes, a uniform pressure was applied to it to provide rapid haemostasis by forming a strong, fibrin clot adjacent to the tissue surface. Tachosil was placed alternately once in the left, once in the right obturator fossa, so that each of the patients participating in the study could be their own control.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Allocation was communicated by telephone after informed consent had been obtained and after lymphadenectomy had been completed. Outcome assessment was performed by the independent reviewers. Outcome assessors were blinded to the treatment allocation.
measure: The incidence and volume of lymphocele.
time frame: 1 year
description: Number of participants with lymphocele as assessed by USG scan at 1,6,30 days and the drainage volume in ml with/without Tachosil assessed by USG scan at 1,2,6,30 days
measure: The incidence of lymphocele after adjuvant treatment
time frame: 1 year
description: Number of participants with lymphocele as assessed by USG scan after complement adjuvant treatament
arm group label: TACHOSIL GROUP
arm group type: Active Comparator
description: Surgical procedures were performed by four doctors with extensive experience in oncological gynecology. A TachoSil® absorbable patch of 4.8x4.8 cm was attached, once, intraoperatively to one side of the obturator fossa (study group). Specific drainage of the retroperitoneum was performed.
arm group label: GROUP WITHOUT TACHOSIL
arm group type: No Intervention
description: The same patient constituted also control group, because no TachoSil® absorbable patche was used on the second side of lymphadenectomy. Specific drainage of the retroperitoneum was performed.
intervention type: Biological
intervention name: TACHOSIL GROUP
arm group label: TACHOSIL GROUP
other name: NCT01192022
criteria: 
gender: Female
gender based: Yes
gender description: Women with cervical or endometrial cancer age between 18 and 70 years signed a written informed consent
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Tomasz Rechberger, Prof
role: Principal Investigator
affiliation: IInd Department of Gynecology, Medical University of Lublin, Poland
facility: 
country: Poland
citation: Tinelli A, Giorda G, Manca C, Pellegrino M, Prudenzano R, Guido M, Dell'Edera D, Malvasi A. Prevention of lymphocele in female pelvic lymphadenectomy by a collagen patch coated with the human coagulation factors: a pilot study. J Surg Oncol. 2012 Jun 15;105(8):835-40. doi: 10.1002/jso.22110. Epub 2011 Oct 10.
PMID: 21987409
citation: Tinelli A, Mynbaev OA, Tsin DA, Giorda G, Malvasi A, Guido M, Nezhat FR. Lymphocele prevention after pelvic laparoscopic lymphadenectomy by a collagen patch coated with human coagulation factors: a matched case-control study. Int J Gynecol Cancer. 2013 Jun;23(5):956-63. doi: 10.1097/IGC.0b013e31828eeea4.
PMID: 23574881
responsible party type: Principal Investigator
investigator affiliation: Medical University of Lublin
investigator full name: Paweł Miotła
investigator title: Clinical Proffesor
mesh term: Uterine Cervical Neoplasms
mesh term: Endometrial Neoplasms
mesh term: Lymphocele
sharing ipd: Yes
ipd description: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
ipd info type: Study Protocol
ipd time frame: from now to ongoing
ipd access criteria: from the corresponding author on reasonable request.