<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/NCT03789799</url>
  </required_header>
  <id_info>
    <org_study_id>ISTIAB-1</org_study_id>
    <nct_id>NCT03789799</nct_id>
  </id_info>
  <brief_title>Effects of Microcrystalline Titanium Dioxide With Covalently Linked Monovalent Silver Ions on Complications After Total Hysterectomy</brief_title>
  <acronym>ISTIAB-1</acronym>
  <official_title>Randomized Controlled Trial on the Use of Microcrystalline Titanium Dioxide With Covalently Linked Monovalent Silver Ions (TIAB) in the Formulation of Vaginal Capsules in the Prevention of Complications After Total Hysterectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università degli Studi dell'Insubria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Università degli Studi dell'Insubria</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Total hysterectomy is one of the most performed surgical procedures in the world and it is&#xD;
      associated with post-operative complications. The postoperative morbidity rate is estimated&#xD;
      to vary from 3% to 8% with a readmission rate of 5-7%. The most frequent postoperative&#xD;
      complications are urinary tract infections, wound infection of the vaginal vault, vault&#xD;
      cellulitis, bleeding, suture dehiscence, pelvic abscess. The introduction of routine&#xD;
      antibiotic prophylaxis has significantly reduced the risk of infectious complications, which&#xD;
      however remains higher than other &quot;clean&quot; surgery, mainly due to contamination by the vaginal&#xD;
      bacterial flora. In this scenario, the introduction of adjuvant factors acting on bacterial&#xD;
      flora, can contribute to reduce the risk of post-surgical complications.&#xD;
&#xD;
      The cationic silver ions (Ag +) stabilized by covalent link with Titanium dioxide (TiO2), the&#xD;
      TIAB, maximizes the properties of silver by optimizing the antibiotic action and disruptive&#xD;
      properties of the pathogenic biofilm of bacteria and fungi. Thanks to these properties, TIAB&#xD;
      is able to enhance the antibiotic action by reducing the risk of antibiotic resistance and&#xD;
      recurrent infections linked to the biofilm. Re-establishing the optimal vaginal&#xD;
      microenvironment represents a fundamental step reducing the risk of infections in the&#xD;
      surgical site, since the vagina is a non-sterile environment populated by bacterial species&#xD;
      that can generate biofilm and potentially infect the site of surgery. In addition to&#xD;
      microbicidal and disruptive biofilm activity, TIAB has demonstrated a direct action on tissue&#xD;
      regeneration processes by stimulating the production of collagen and its modeling.&#xD;
&#xD;
      Different clinical trials have reported a cicatrizing and re-epithelializing action of TIAB&#xD;
      administered vaginally in the context of cervical conization for pathology related to HPV.&#xD;
      Without showing any notable adverse effects or a negative action on lactobacillary flora with&#xD;
      an overall good therapy tolerance by patients.&#xD;
&#xD;
      On the basis of the available evidence, we conduct a randomized controlled clinical trial to&#xD;
      determine if TIAB treatment in the formulation of vaginal capsules TIAGIN (TIAB&#xD;
      (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium&#xD;
      Hyaluronate, Aloe Barbadensis Extract) is able to reduce the incidence of infectious&#xD;
      complications, that are related to altered healing of post-hysterectomy vaginal suture.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2019</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>
    <intervention_model_description>Randomized controlled double-blind trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>TIAGIN and placebo will be provided in identical non-distinguishable packaging and formulations. To each pack a unique random ID will be assigned based on an independently generated random scheme (www.randomization.com). Patients will blindly receive consecutively a single pack of 10 vaginal capsules. The same blinding procedure will also be present for health professionals (double-blind study) as only the manufacturer will be aware of the contents of the pack. For each enrolled patient, the patient ID will be associated to the packaging ID, the maintenance of the confidentiality of such data will be the responsibility of the Principal Investigator, to which the contents of the pack will be revealed only at the end of the study for the final data analysis.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Vaginal bleeding</measure>
    <time_frame>Between the 10th post operative day and the 30th post operative day</time_frame>
    <description>at least one episode of red vaginal blood loss</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaginal vault infection</measure>
    <time_frame>Between the first post operative day and the 30th post operative day</time_frame>
    <description>at least one episode of inflammation and infection in the vaginal vault suture requiring antibiotic therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Urinary tract infection</measure>
    <time_frame>Between the 10th post operative day and the 30th post operative day</time_frame>
    <description>at least one episode of signs and symptoms requiring empiric antibiotic therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dehiscence of vaginal vault suture</measure>
    <time_frame>Between the 10th post operative day and the 30th post operative day</time_frame>
    <description>Dehiscence of vaginal vault suture requiring repeat surgery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Readmission</measure>
    <time_frame>Between the day of discharge and the 30th post operative day</time_frame>
    <description>At least one episode of readmission related to postoperative complications</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Between the first post operative day and the 30th post operative day</time_frame>
    <description>Adverse events due to the use of vaginal capsule therapy: erythema, vaginal and vulvar pruritus, dermatitis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Infection</condition>
  <condition>Bleeding</condition>
  <condition>Complication, Postoperative</condition>
  <arm_group>
    <arm_group_label>TIAB treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>From the first postoperative day for ten days, single vaginal capsule per day of TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>From the first postoperative day for ten days, single vaginal capsule per day of sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>TIAB: microcrystalline titanium dioxide with covalently linked monovalent silver ions</intervention_name>
    <description>TIAGIN vaginal capsule, composition: TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, Aloe Barbadensis Extract</description>
    <arm_group_label>TIAB treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo vaginal capsule, composition: Sodium Hyaluronate, Aloe Barbadensis Extract</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women underwent laparoscopic total hysterectomy for benign gynecological pathology&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women underwent non-laparoscopic total hysterectomy&#xD;
&#xD;
          -  Women underwent laparoscopic total hysterectomy for malignant pathology&#xD;
&#xD;
          -  Patients with diabetes mellitus in insulin therapy&#xD;
&#xD;
          -  Smoking patients&#xD;
&#xD;
          -  Patients suffering from chronic rheumatic diseases or chronic diseases not in adequate&#xD;
             control.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simone Garzon, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università degli Studi dell'Insubria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio Simone Laganà, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università degli Studi dell'Insubria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fabio Ghezzi, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università degli Studi dell'Insubria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jvan Casarin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università degli Studi dell'Insubria</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Simone Garzon, M.D.</last_name>
    <phone>+39 347 0782287</phone>
    <email>sgarzon@studenti.uninsubria.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Antonio Simone Laganà, M.D.</last_name>
    <phone>‭+39 329 6279579‬</phone>
    <email>antoniosimone.lagana@asst-settelaghi.it</email>
  </overall_contact_backup>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università degli Studi dell'Insubria</investigator_affiliation>
    <investigator_full_name>Simone Garzon</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postoperative Complications</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Titanium dioxide</mesh_term>
  </intervention_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/NCT03789799
org study id: ISTIAB-1
nct id: NCT03789799
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Total hysterectomy is one of the most performed surgical procedures in the world and it is
      associated with post-operative complications. The postoperative morbidity rate is estimated
      to vary from 3% to 8% with a readmission rate of 5-7%. The most frequent postoperative
      complications are urinary tract infections, wound infection of the vaginal vault, vault
      cellulitis, bleeding, suture dehiscence, pelvic abscess. The introduction of routine
      antibiotic prophylaxis has significantly reduced the risk of infectious complications, which
      however remains higher than other "clean" surgery, mainly due to contamination by the vaginal
      bacterial flora. In this scenario, the introduction of adjuvant factors acting on bacterial
      flora, can contribute to reduce the risk of post-surgical complications.

      The cationic silver ions (Ag +) stabilized by covalent link with Titanium dioxide (TiO2), the
      TIAB, maximizes the properties of silver by optimizing the antibiotic action and disruptive
      properties of the pathogenic biofilm of bacteria and fungi. Thanks to these properties, TIAB
      is able to enhance the antibiotic action by reducing the risk of antibiotic resistance and
      recurrent infections linked to the biofilm. Re-establishing the optimal vaginal
      microenvironment represents a fundamental step reducing the risk of infections in the
      surgical site, since the vagina is a non-sterile environment populated by bacterial species
      that can generate biofilm and potentially infect the site of surgery. In addition to
      microbicidal and disruptive biofilm activity, TIAB has demonstrated a direct action on tissue
      regeneration processes by stimulating the production of collagen and its modeling.

      Different clinical trials have reported a cicatrizing and re-epithelializing action of TIAB
      administered vaginally in the context of cervical conization for pathology related to HPV.
      Without showing any notable adverse effects or a negative action on lactobacillary flora with
      an overall good therapy tolerance by patients.

      On the basis of the available evidence, we conduct a randomized controlled clinical trial to
      determine if TIAB treatment in the formulation of vaginal capsules TIAGIN (TIAB
      (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium
      Hyaluronate, Aloe Barbadensis Extract) is able to reduce the incidence of infectious
      complications, that are related to altered healing of post-hysterectomy vaginal suture.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled double-blind trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: TIAGIN and placebo will be provided in identical non-distinguishable packaging and formulations. To each pack a unique random ID will be assigned based on an independently generated random scheme (www.randomization.com). Patients will blindly receive consecutively a single pack of 10 vaginal capsules. The same blinding procedure will also be present for health professionals (double-blind study) as only the manufacturer will be aware of the contents of the pack. For each enrolled patient, the patient ID will be associated to the packaging ID, the maintenance of the confidentiality of such data will be the responsibility of the Principal Investigator, to which the contents of the pack will be revealed only at the end of the study for the final data analysis.
measure: Vaginal bleeding
time frame: Between the 10th post operative day and the 30th post operative day
description: at least one episode of red vaginal blood loss
measure: Vaginal vault infection
time frame: Between the first post operative day and the 30th post operative day
description: at least one episode of inflammation and infection in the vaginal vault suture requiring antibiotic therapy
measure: Urinary tract infection
time frame: Between the 10th post operative day and the 30th post operative day
description: at least one episode of signs and symptoms requiring empiric antibiotic therapy
measure: Dehiscence of vaginal vault suture
time frame: Between the 10th post operative day and the 30th post operative day
description: Dehiscence of vaginal vault suture requiring repeat surgery
measure: Readmission
time frame: Between the day of discharge and the 30th post operative day
description: At least one episode of readmission related to postoperative complications
measure: Adverse events
time frame: Between the first post operative day and the 30th post operative day
description: Adverse events due to the use of vaginal capsule therapy: erythema, vaginal and vulvar pruritus, dermatitis.
arm group label: TIAB treatment
arm group type: Experimental
description: From the first postoperative day for ten days, single vaginal capsule per day of TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule.
arm group label: Placebo
arm group type: Placebo Comparator
description: From the first postoperative day for ten days, single vaginal capsule per day of sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule.
intervention type: Other
intervention name: TIAB: microcrystalline titanium dioxide with covalently linked monovalent silver ions
description: TIAGIN vaginal capsule, composition: TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, Aloe Barbadensis Extract
arm group label: TIAB treatment
intervention type: Other
intervention name: Placebo
description: Placebo vaginal capsule, composition: Sodium Hyaluronate, Aloe Barbadensis Extract
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Simone Garzon, M.D.
role: Principal Investigator
affiliation: Università degli Studi dell'Insubria
last name: Antonio Simone Laganà, M.D.
role: Principal Investigator
affiliation: Università degli Studi dell'Insubria
last name: Fabio Ghezzi, M.D.
role: Principal Investigator
affiliation: Università degli Studi dell'Insubria
last name: Jvan Casarin, M.D.
role: Principal Investigator
affiliation: Università degli Studi dell'Insubria
last name: Simone Garzon, M.D.
phone: +39 347 0782287
email: sgarzon@studenti.uninsubria.it
last name: Antonio Simone Laganà, M.D.
phone: ‭+39 329 6279579‬
email: antoniosimone.lagana@asst-settelaghi.it
responsible party type: Principal Investigator
investigator affiliation: Università degli Studi dell'Insubria
investigator full name: Simone Garzon
investigator title: Principal Investigator
mesh term: Postoperative Complications
mesh term: Titanium dioxide
sharing ipd: Undecided