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D-PLEX 311: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04233424
Recruitment Status : Completed
First Posted : January 18, 2020
Last Update Posted : September 29, 2022
Sponsor:
Information provided by (Responsible Party):
PolyPid Ltd.

Tracking Information
First Submitted Date  ICMJE January 6, 2020
First Posted Date  ICMJE January 18, 2020
Last Update Posted Date September 29, 2022
Actual Study Start Date  ICMJE June 24, 2020
Actual Primary Completion Date September 2, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2022)
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 ]
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)].
Original Primary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
  • 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 ]
    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)].
  • Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional [ Time Frame: By day 60 post surgery ]
    Safety parameters will be evaluated by adverse events
  • Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional [ Time Frame: By day 60 post surgery ]
    Incisional wound healing will be assessed by a blinded Investigator, using a visual examination as well as Modified Vancouver Scar Scale wound assessment questionnaires
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
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 ]
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)].
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 11, 2022)
  • Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional [ Time Frame: By day 60 post surgery ]
    Safety parameters will be evaluated by adverse events
  • All-cause mortality and re-interventions in the target incision due to SSI [ Time Frame: By day 30 post surgery ]
    All-cause mortality and re-intervention at the primary incision site (target) due to suspected SSI or due to poor wound healing, including wound dehiscence (as verified by the blinded adjudication committee), within 30 days post index surgery will be analysed as treatment failure.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE D-PLEX 311: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection
Official Title  ICMJE D-PLEX 311- 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 I)
Brief Summary 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.
Detailed Description

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 resection, with or without a stoma, that includes at least 1 incision that is > 10 cm (target incision). Eligible and willing subjects will be randomly allocated into 2 blinded study arms D-PLEX with SOC or SOC alone.

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 well as physicians assessment of the incisional wound.

The final number of subjects will be determined following a comparative interim analysis for an early efficacy or futility stop or unblinded sample size re-estimation: when about 750 subjects will complete their 30 days (1 month) follow-up and evaluated for primary endpoint

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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.

The final number of subjects will be determined following a comparative interim analysis for an early efficacy or futility stop or unblinded sample size re-estimation: when about 750 subjects will complete their 30 days (1 month) follow-up and evaluated for primary endpoint.

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.

Primary Purpose: Prevention
Condition  ICMJE
  • Surgical Site Infection
  • Colon Surgery
  • Abdominal Surgery
  • Post-Op Infection
Intervention  ICMJE
  • Drug: D-PLEX
    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.
  • Other: Standard of Care (SoC)
    prophylactic, pre-operation per institution guidelines
Study Arms  ICMJE
  • Experimental: D-PLEX+SoC
    D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment
    Intervention: Drug: D-PLEX
  • Standard of care
    The SoC for prophylactic antibiotic treatment is based on international guidelines
    Intervention: Other: Standard of Care (SoC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 31, 2022)
950
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2020)
1116
Actual Study Completion Date  ICMJE September 2, 2022
Actual Primary Completion Date September 2, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  1. Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision that is > 10cm (target incision).
  2. Subjects are preoperative hemodynamically stable
  3. Male or non-pregnant female.
  4. Female of child-bearing potential should have a negative pregnancy test prior to index procedure.
  5. Subjects' age 18 years old and above at screening.
  6. Subjects who sign the written Informed Consent Form.
  7. Subjects who are willing and able to participate and meet all study requirements.
  8. Survival expectancy of at least 60 days post randomization

EXCLUSION CRITERIA

  1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, ect.)
  2. Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization.
  3. Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past 1 week prior to randomization, excluding pre-operative prophylaxis.
  4. Subjects undergoing concomitant major procedures in addition to the abdominal surgery, including concomitant repair of ventral hernia. Salpingo-oophorectomy and cholecystectomy are allowed.
  5. Subjects who received any anti-cancer treatment within the last 4 weeks of surgery.
  6. Subjects who received radiation for colorectal cancer to the abdomen area, prior to the planned abdominal surgery.
  7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past 4 weeks prior to randomization.
  8. Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients.
  9. Subjects with known allergies to more than 3 substances (an allergy questionnaire will be completed during the screening process).
  10. Subjects with history of severe allergic reaction to any substance, having required treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion of the PI is at high risk of developing severe allergic reactions.
  11. Subjects with End Stage Renal Disease (ESRD/ CKD stage 5).
  12. Subjects with severe hepatic impairment.
  13. Subjects with chronic urticaria.
  14. Subjects diagnosed with CVA within the past 6 months prior to randomization.
  15. Subjects who underwent any abdominal surgery and current planned index surgery involves re-opening the scar of a prior abdominal surgery performed within the last 3 years.
  16. Any subject with an active malignancy, other than resectable non-metastatic colorectal cancer, that is the reason for the index surgery, or carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin, or a malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least 3 years.
  17. Subjects with other concurrent severe and/or uncontrolled medical conditions.
  18. Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study.
  19. Chronic alcoholic or drug abuse subjects.
  20. Pregnant or breast-feeding women or women of child-bearing age who refuse or are prohibited of using an effective contraceptive method of birth control throughout study participation, including the safety follow-up period.
  21. Subjects who received any investigational drug within 30 days or 5 half-lives prior to randomization to the study (whichever is longer) and through the study.
  22. Subjects participating in any other interventional study.
  23. Subjects, who in the opinion of Investigator, are not eligible to participate in the study and/or to comply with the protocol requirements (e.g. due to a cognitive or medical condition).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Croatia,   Czechia,   Hungary,   Israel,   Moldova, Republic of,   Romania,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04233424
Other Study ID Numbers  ICMJE D-PLEX 311
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party PolyPid Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE PolyPid Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PolyPid Ltd.
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP