Prevention of post abdominal surgery incisional infection. MedDRA version: 20.0 Level: LLT Classification code 10078408 Term: Surgical site infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: D-PLEX
Product Code: NA
Pharmaceutical Form: Powder for implantation paste
INN or Proposed INN: DOXYCYCLINE HYCLATE
CAS Number: 24390-14-5
Current Sponsor code: NA
Concentration unit: %
Sponsors
PolyPid Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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 = 7cm (target incision). 2.Subjects are preoperative hemodynamically stable. (BP=180/110 and =90/60 mmHg, and HR=100 and =60 bpm, and temperature =38.50C and =35.50C). 3.Male or non-pregnant female. 4.Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure. Note: All female subjects of child¿bearing potential must agree to use a highly effective method of contraception consistently and correctly for the duration of the study. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1000 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
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, etc.) 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 one week prior to randomization, excluding pre-operative prophylaxis or antibiotics for the treatment of the disease that is the indication for surgery. 4. Subjects undergoing concomitant major procedures in addition to the abdominal surgery, including concomitant repair for 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 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 condition. 18. Psychiatric or any other disorder that compromises the 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the anti¿infective efficacy of D¿PLEX administered concomitantly with the Standard of Care (SoC) over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and/or deep infection, in the target incision, compared to the SoC treated control arm and to assess the safety of D¿PLEX administered concomitantly with the Standard of Care (SoC).;Secondary Objective: Not applicable;Primary end point(s): Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee. [abdominal incisional infection is composed defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)]. All-cause mortality and re-interventions through the abdominal incision (target) within 30 days post index surgery will be analysed as treatment failure. Reintervention is defined as re-opening of the same target incision, used for the original index surgery, in the operation room (OR). An independent and blinded adjudication committee will review each case suspected for SSI and will adjudicate if meets the SSI endpoint criteria. ;Timepoint(s) of evaluation of this end point: 30 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key endpoints: Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event only, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee. Number (percent) of subjects with at least 1 score of ASEPSIS > 20, within 30 days post abdominal surgery. Additional endpoints: Incidence of SSSI during 30 days post index surgery. Incidence of DSSI during 30 days post index surgery. -All cause mortality rate within 30 days post randomization. -All cause mortality rate within 60 days post randomization. -Time to adjudicated SSI during 30 days post index surgery. -Number (percent) of subjects re-admitted during 30 days post-surgery (for any reason) that have experienced adjudicated SSI during this re-admission. -Number (percent) of subjects who experienced at least 1 surgical re-intervention due to adjudicated SSIs during 30 days post-surgery. SSI related Additional Endpoints: -Number (percent) of subjects with adjudicated SSI where at least one Doxycycline¿resistant bacteria have grown in bacteriology tests. -Number (percent) of Doxycycline¿resistant bacteria out of all bacteria that were cultured during bacteriology test from subjects with adjudicated SSI. -Number (percent) of subjects who experienced adjudicated SSI during 30 days post¿surgery that were treated by IV antibiotic. -Number of IV antibiotic treatment days, administered to subjects who experience adjudicated SSI during 30 days postsurgery. -Average of subjects¿ cumulative ASEPSIS assessment score (AUC) for subjects with adjudicated SSI during 30 days. -Number (percent) of subjects with at least 1 score of ASEPSIS > 20 in subject with adjudicated SSI within 30 days post abdominal index surgery. Identification of an SSI will be based on CDC/NHSN Patient Safety Component Manual criteria (January 2020, chapter 9);Timepoint(s) of evaluation of this end point: 30 days, 60 days | — |
Countries
Germany, Hungary, Ireland, Israel, Italy, Poland, Portugal, Serbia, United States
Contacts
Public ContactPolyPid Clinical Department
PolyPid Ltd.
Outcome results
None listed