<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/NCT04411199</url>
  </required_header>
  <id_info>
    <org_study_id>D-PLEX 312</org_study_id>
    <nct_id>NCT04411199</nct_id>
  </id_info>
  <brief_title>D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)</brief_title>
  <acronym>D-PLEX312</acronym>
  <official_title>D-PLEX 312 - Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX In Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PolyPid Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PolyPid Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double&#xD;
      Blind Study to Assess Efficacy and Safety of D-PLEX Administered Concomitantly with the&#xD;
      Standard of Care (SoC), Compared to a SoC Treated Control Arm, in Prevention of Post&#xD;
      Abdominal Surgery Incisional Infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      D-PLEX is a new formulation of extended controlled release of Doxycycline in the applied area&#xD;
      for about 30 days. This study is aimed to assess the safety and efficacy of D-PLEX in&#xD;
      prevention of post abdominal surgery incisional infection.&#xD;
&#xD;
      The study population includes male and female, 18 years old and above at screening,&#xD;
      undergoing an elective colorectal surgery involving colon or rectal resection, with or&#xD;
      without a stoma formation, that includes at least 1 incision that is ≥ 7cm (target incision).&#xD;
&#xD;
      Eligible and willing subjects will be randomly allocated into 2 blinded study arms, either to&#xD;
      the investigational arm (D-PLEX + SoC) or to the control arm (SoC only) in a 1:1 ratio.&#xD;
      Subjects will be stratified by incisional length (7cm ≤10 cm, &gt;10 ≤20cm, &gt;20cm), type of&#xD;
      prophylactic SoC (IV antibiotic only, IV antibiotic with mechanical bowel preparation or IV&#xD;
      antibiotic with oral antibiotics combined with mechanical bowel preparation) and by region&#xD;
      (US versus Europe + Israel).&#xD;
&#xD;
      D-PLEX will be applied during the surgery at the final stage of incision closure. All&#xD;
      patients will be followed up for additional 5 visits over 2 months, for safety and incisional&#xD;
      wound assessment. This will include blood tests for hematology and chemistry as well as&#xD;
      physician's assessment of the incisional wound.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 6, 2020</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</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>Males and females, &gt;18 years old, undergoing scheduled abdominal colon surgery involving resection and anastomosis or a stoma, who meet the inclusion criteria and none of the exclusion criteria and provide signed informed consent will be enrolled in the study.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>This is a double-blind clinical trial. The sponsor, the subjects, outcomes assessor and all staff involved in the collection and recording of the clinical and laboratory data, based on which the independent adjudication committee will perform their assessment, will be blind to treatment assignment. In addition, all aspects of data management and clean-up will be done in blinded datasets.&#xD;
The study site personnel, who perform the index surgery (Operation room staff), will be trained not to disclose the treatment arm to the blinded Investigator, to the subject, his/her family, to other health care providers not present during the surgery or to the study Sponsor representatives. Wound assessment throughout the study follow-up visits will be done by a blinded Investigator, that will not be involved in the surgery. An emergency card containing the Study Name, NIH number, Center Name/number, PI's name and contact details will be provided to the subjects.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and deep infection, in the target incision(s), compared to the SoC treated control.</measure>
    <time_frame>By day 30 post surgery</time_frame>
    <description>Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery. [abdominal incisional infection is composed of Deep Incisional Surgical Site Infection (DSSI) and Superficial Incisional Surgical Site Infection (SSSI)].within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.&#xD;
All-cause mortality and re-interventions in the target incision within 30 days post index surgery will be analysed as treatment failure.&#xD;
Incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.&#xD;
[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of D-PLEX in Prevention of Post Abdominal Surgery</measure>
    <time_frame>By day 60 post surgery</time_frame>
    <description>Safety parameters will be evaluated by adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional</measure>
    <time_frame>By day 60 post surgery</time_frame>
    <description>Incisional wound healing will be assessed by a blinded Investigator, using a visual examination as well as Modified Vancouver Scar Scale wound assessment questionnaires. The questionnaire has a numeric scale from 0-4 in Vascularity, Pigmentation, Pliability and height</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of Infection rate in patient undergoing abdominal colon surgery</measure>
    <time_frame>At study visits: day 1, day 5, day 14 and day 30 post surgery</time_frame>
    <description>Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.&#xD;
[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">900</enrollment>
  <condition>Surgical Site Infection</condition>
  <condition>Colon Surgery</condition>
  <condition>Abdominal Surgery</condition>
  <condition>Post-Op Infection</condition>
  <arm_group>
    <arm_group_label>D-PLEX+SoC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The SoC for prophylactic antibiotic treatment is based on international guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>D-PLEX</intervention_name>
    <description>D-PLEX is a new formulation of extended release of Doxycycline. Each 5g D-PLEX vial contains 54.6mg Doxycycline free base (1.09%), which is equivalent to 63mg Doxycycline hyclate (1.26%). D-PLEX is supplied as a sterile powder to be reconstituted to paste in the operating room, using standard aseptic techniques and is intended for single administration. The non-active components of the extended release antibiotic formulation are β Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.</description>
    <arm_group_label>D-PLEX+SoC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care (SoC)</intervention_name>
    <description>prophylactic, pre-operation per institution guidelines</description>
    <arm_group_label>D-PLEX+SoC</arm_group_label>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects undergoing an elective colorectal surgery involving resection, with or&#xD;
             without a stoma formation, that includes at least 1 abdominal incision that is ≥ 7cm&#xD;
             (target incision).&#xD;
&#xD;
          2. Subjects are preoperative hemodynamically stable.&#xD;
&#xD;
          3. Male or non-pregnant female.&#xD;
&#xD;
          4. Female of child-bearing potential should have a negative pregnancy test prior to index&#xD;
             procedure.&#xD;
&#xD;
          5. Subjects' age 18 years old and above at screening.&#xD;
&#xD;
          6. Subjects who sign the written Informed Consent Form.&#xD;
&#xD;
          7. Subjects who are willing and able to participate and meet all study requirements.&#xD;
&#xD;
          8. Survival expectancy of at least 60 days post randomization .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Subjects who meet any of the following exclusion criteria are prohibited from&#xD;
        participating in the study:&#xD;
&#xD;
          1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or&#xD;
             any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic&#xD;
             colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, etc.)&#xD;
&#xD;
          2. Subjects who underwent an intra-abdominal surgery within the last 6 months prior to&#xD;
             randomization.&#xD;
&#xD;
          3. Subjects with any preoperative active infection or who are receiving any antibiotic&#xD;
             therapy in the past 1 week prior to randomization, excluding pre-operative&#xD;
             prophylaxis.&#xD;
&#xD;
          4. Subjects undergoing concomitant major procedures in addition to the abdominal surgery,&#xD;
             including concomitant repair of ventral hernia. Salpingo-oophorectomy and&#xD;
             cholecystectomy are allowed.&#xD;
&#xD;
          5. Subjects who received any anti-cancer treatment within the last 4 weeks of surgery.&#xD;
&#xD;
          6. Subjects who received radiation for colorectal cancer to the abdomen area, prior to&#xD;
             the planned abdominal surgery.&#xD;
&#xD;
          7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during&#xD;
             the past 4 weeks prior to randomization.&#xD;
&#xD;
          8. Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs&#xD;
             or to the D-PLEX's excipients.&#xD;
&#xD;
          9. Subjects with known allergies to more than 3 substances (an allergy questionnaire will&#xD;
             be completed during the screening process).&#xD;
&#xD;
         10. Subjects with history of severe allergic reaction to any substance, having required&#xD;
             treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion&#xD;
             of the PI is at high risk of developing severe allergic reactions.&#xD;
&#xD;
         11. Subjects with End Stage Renal Disease (ESRD/ CKD stage 5).&#xD;
&#xD;
         12. Subjects with severe hepatic impairment.&#xD;
&#xD;
         13. Subjects with chronic urticaria.&#xD;
&#xD;
         14. Subjects diagnosed with CVA within the past 6 months prior to randomization.&#xD;
&#xD;
         15. Subjects who underwent any abdominal surgery and current planned index surgery&#xD;
             involves re-opening the scar of a prior abdominal surgery performed within the last 3&#xD;
             years.&#xD;
&#xD;
         16. Any subject with an active malignancy, other than resectable non-metastatic colorectal&#xD;
             that is the reason for the index surgery, or carcinoma in situ (or other cancer &quot;in&#xD;
             situ = Stage 0&quot;), or squamous cell carcinoma of the skin, or basal cell carcinoma of&#xD;
             the skin, or a malignancy that has not been in complete clinical remission and without&#xD;
             maintenance chemo or immunotherapy for at least 3 years.&#xD;
&#xD;
         17. Subjects with other concurrent severe and/or uncontrolled medical condition.&#xD;
&#xD;
         18. Psychiatric or any other disorder that compromises ability to provide informed consent&#xD;
             for participation in this study.&#xD;
&#xD;
         19. Chronic alcoholic or drug abuse subjects.&#xD;
&#xD;
         20. Pregnant or breast-feeding women or women of child-bearing age who refuse or are&#xD;
             prohibited of using an effective contraceptive method of birth control throughout&#xD;
             study participation, including the safety follow-up period.&#xD;
&#xD;
         21. Subjects who received any investigational drug within 30 days or 5 half-lives prior to&#xD;
             randomization to the study (whichever is longer) and through the study.&#xD;
&#xD;
         22. Subjects participating in any other interventional study.&#xD;
&#xD;
         23. Subjects who in the opinion of the Investigator, are not eligible to participate in&#xD;
             the study and/or to comply with the protocol requirements (e.g. due to a cognitive or&#xD;
             medical condition).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Lital Weinfeld Bergman, COM</last_name>
    <phone>+972 74-7195700</phone>
    <email>lital.wb@polypid.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Radhika Smith, Dr.</last_name>
      <phone>314-362-2646</phone>
      <email>radhikasmith@wustl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Fichera, Dr.</last_name>
      <phone>469-800-7180</phone>
      <email>Alessandro.Fichera@BSWHealth.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HD Research LLC / Memorial Hermann Southeast Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77089</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adnan Rafiq, Dr.</last_name>
      <phone>713-480-3028</phone>
      <email>hminkowitz@lotuscr.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Uzsoki utcai Kórház, Sebészeti Osztály</name>
      <address>
        <city>Budapest</city>
        <zip>1145</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristof Dede, Dr.</last_name>
      <phone>36 1 467 3700</phone>
      <phone_ext>1634</phone_ext>
      <email>dede.kristof@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Bács-Kiskun Megyei Kórház</name>
      <address>
        <city>Kecskemét</city>
        <zip>6000</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>László Sikorszki, Prof.</last_name>
      <phone>36 76 516 700</phone>
      <phone_ext>5154</phone_ext>
      <email>sikorszkil@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pest Megyei Flór Ferenc Kórház</name>
      <address>
        <city>Kistarcsa</city>
        <zip>2143</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zsolt T. Csapo, Dr.</last_name>
      <phone>(36) 28 507 600</phone>
      <email>csapo.zsolt@florhosp.hu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház</name>
      <address>
        <city>Nyíregyháza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lajos B. Toth, Dr.</last_name>
      <phone>(36) 42 599-700</phone>
      <phone_ext>1210</phone_ext>
      <email>dr.toth.lajos.barna@szszbmk.hu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Szegedi Tudományegyetem Általános Orvostudományi Kar Szent-Györgyi Albert Orvostudományi Központ</name>
      <address>
        <city>Szeged</city>
        <zip>6725</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>György Lazar, Prof.</last_name>
      <phone>(36) 62 545 701</phone>
      <email>gylazar@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Szent Borbála Kórház</name>
      <address>
        <city>Tatabánya</city>
        <zip>2800</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Balázs Banky, Prof.</last_name>
      <phone>(36) 34 515 488</phone>
      <phone_ext>407</phone_ext>
      <email>bankybalazs@tatabanyakorhaz.hu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Soroka Medical Center</name>
      <address>
        <city>Be'er Sheva</city>
        <zip>8457108</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Czeiger, Dr.</last_name>
      <phone>972-54-4761408</phone>
      <email>DudyC@CLALIT.org.il</email>
    </contact>
    <contact_backup>
      <last_name>Orian Sinhon</last_name>
      <phone>972-8-6292822</phone>
      <email>oriansi@clalit.org.il</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Bnai Zion Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3339419</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gideon Sroka, Dr.</last_name>
      <phone>04-8359137</phone>
      <email>gideon.sroka@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Carmel Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3436212</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wissam Khouri, Dr.</last_name>
      <phone>04-8250490</phone>
      <email>wisamk@clalit.org.il</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek MC</name>
      <address>
        <city>Jerusalem</city>
        <zip>9372212</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Petachia Reissman, Prof.</last_name>
      <phone>02-6666310</phone>
      <email>reissman@szmc.org.il</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UCK im. Prof. K. Gibinskiego, Oddziat Chirurgii Przewodu Pokarmowego</name>
      <address>
        <city>Katowice</city>
        <zip>40-752</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Slawomir Mrowiec, Dr.</last_name>
      <phone>+48 32 7894251</phone>
      <email>mrowasm@poczta.onet.pl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Szpital im. M. Curie-Skłodowskiej w Ostrowie Mazowieckim</name>
      <address>
        <city>Wołomin</city>
        <zip>05-200</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Przemyslaw Ciesielski, Dr.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wojewódzki Szpital Specjalistyczny we Wrocławiu</name>
      <address>
        <city>Wrocław</city>
        <zip>51-124</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacek Śmigielski, Prof.</last_name>
      <phone>+48 60 1365926</phone>
      <email>smiglo@mp.pl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Med.-Gastr Łódź</name>
      <address>
        <city>Łódź</city>
        <zip>91-032</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arkadiusz Mamos, Dr.</last_name>
      <phone>+48 42 2582223</phone>
      <email>arkadiusz.mamos@medgastr.pl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinical Centre Kragujevac, General and Thoracic Surgery Clinic</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Radisav Bogojevic, Dr.</last_name>
      <phone>(00-381)-64-132-8479</phone>
      <email>drrasabogojevic@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinical Centre Nis, Clinic for Digestive Surgery</name>
      <address>
        <city>Nis</city>
        <zip>18108</zip>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Milica Nestorovic, Dr.</last_name>
      <phone>(00-381)-63-590-900</phone>
      <email>milica20@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institute of Oncology of Vojvodina, Clinic of Operative Oncology</name>
      <address>
        <city>Sremska Kamenica</city>
        <zip>21204</zip>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mladjan Protic, Dr.</last_name>
      <phone>(00-381)-64-125-3308</phone>
      <email>mlprotic@gmail.com; protic.mladjan@onk.ns.ac.rs</email>
    </contact>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Poland</country>
    <country>Serbia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>October 25, 2022</last_update_submitted>
  <last_update_submitted_qc>October 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Surgical site infection</keyword>
  <keyword>Abdominal surgery</keyword>
  <keyword>Colon and small bowl surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
  </condition_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/NCT04411199
org study id: D-PLEX 312
nct id: NCT04411199
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double
      Blind Study to Assess Efficacy and Safety of D-PLEX Administered Concomitantly with the
      Standard of Care (SoC), Compared to a SoC Treated Control Arm, in Prevention of Post
      Abdominal Surgery Incisional Infection.
D-PLEX is a new formulation of extended controlled release of Doxycycline in the applied area
      for about 30 days. This study is aimed to assess the safety and efficacy of D-PLEX in
      prevention of post abdominal surgery incisional infection.

      The study population includes male and female, 18 years old and above at screening,
      undergoing an elective colorectal surgery involving colon or rectal resection, with or
      without a stoma formation, that includes at least 1 incision that is ≥ 7cm (target incision).

      Eligible and willing subjects will be randomly allocated into 2 blinded study arms, either to
      the investigational arm (D-PLEX + SoC) or to the control arm (SoC only) in a 1:1 ratio.
      Subjects will be stratified by incisional length (7cm ≤10 cm, >10 ≤20cm, >20cm), type of
      prophylactic SoC (IV antibiotic only, IV antibiotic with mechanical bowel preparation or IV
      antibiotic with oral antibiotics combined with mechanical bowel preparation) and by region
      (US versus Europe + Israel).

      D-PLEX will be applied during the surgery at the final stage of incision closure. All
      patients will be followed up for additional 5 visits over 2 months, for safety and incisional
      wound assessment. This will include blood tests for hematology and chemistry as well as
      physician's assessment of the incisional wound.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Males and females, >18 years old, undergoing scheduled abdominal colon surgery involving resection and anastomosis or a stoma, who meet the inclusion criteria and none of the exclusion criteria and provide signed informed consent will be enrolled in the study.
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
masking description: This is a double-blind clinical trial. The sponsor, the subjects, outcomes assessor and all staff involved in the collection and recording of the clinical and laboratory data, based on which the independent adjudication committee will perform their assessment, will be blind to treatment assignment. In addition, all aspects of data management and clean-up will be done in blinded datasets.
The study site personnel, who perform the index surgery (Operation room staff), will be trained not to disclose the treatment arm to the blinded Investigator, to the subject, his/her family, to other health care providers not present during the surgery or to the study Sponsor representatives. Wound assessment throughout the study follow-up visits will be done by a blinded Investigator, that will not be involved in the surgery. An emergency card containing the Study Name, NIH number, Center Name/number, PI's name and contact details will be provided to the subjects.
measure: To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and deep infection, in the target incision(s), compared to the SoC treated control.
time frame: By day 30 post surgery
description: Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery. [abdominal incisional infection is composed of Deep Incisional Surgical Site Infection (DSSI) and Superficial Incisional Surgical Site Infection (SSSI)].within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
All-cause mortality and re-interventions in the target incision within 30 days post index surgery will be analysed as treatment failure.
Incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].
measure: Safety of D-PLEX in Prevention of Post Abdominal Surgery
time frame: By day 60 post surgery
description: Safety parameters will be evaluated by adverse events
measure: Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional
time frame: By day 60 post surgery
description: Incisional wound healing will be assessed by a blinded Investigator, using a visual examination as well as Modified Vancouver Scar Scale wound assessment questionnaires. The questionnaire has a numeric scale from 0-4 in Vascularity, Pigmentation, Pliability and height
measure: Assessment of Infection rate in patient undergoing abdominal colon surgery
time frame: At study visits: day 1, day 5, day 14 and day 30 post surgery
description: Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].
arm group label: D-PLEX+SoC
arm group type: Experimental
description: D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment
arm group label: Standard of Care
arm group type: Other
description: The SoC for prophylactic antibiotic treatment is based on international guidelines
intervention type: Drug
intervention name: D-PLEX
description: D-PLEX is a new formulation of extended release of Doxycycline. Each 5g D-PLEX vial contains 54.6mg Doxycycline free base (1.09%), which is equivalent to 63mg Doxycycline hyclate (1.26%). D-PLEX is supplied as a sterile powder to be reconstituted to paste in the operating room, using standard aseptic techniques and is intended for single administration. The non-active components of the extended release antibiotic formulation are β Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.
arm group label: D-PLEX+SoC
intervention type: Other
intervention name: Standard of Care (SoC)
description: prophylactic, pre-operation per institution guidelines
arm group label: D-PLEX+SoC
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Lital Weinfeld Bergman, COM
phone: +972 74-7195700
email: lital.wb@polypid.com
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country: Hungary
country: Israel
country: Poland
country: Serbia
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection