Abdominal Surgery, Colon Surgery, Post-Op Infection
Conditions
Keywords
Surgical site infection, Abdominal surgery, Colon and small bowl surgery
Brief summary
Subjects who are planned to undergo an abdominal (colon) surgery and who will meet the study entry criteria will be randomly divided into 2 groups: for half D-PLEX will be administered concomitantly with the standard of care (SOC). The other half will receive the Standard of Care treatment. Following the surgery subjects will be followed up for additional 5 visits, at least half are in line with the routine practice of surgery Follow-Ups. Visits will include patient safety and wound assessments.
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. Eligible and willing subjects will be randomly divided, in a single-blinded manner into 2 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, chemistry and pharmacokinetics (PK, for some only) as well as physicians assessment of the incisional wound.
Interventions
OTHERStandard of Care (SoC)
Prophylactic, pre-operation: 1st or 2nd generation of Cephalosporine family, plus Metronidazole. Post-operation: this is each participating center standard practice for this type of procedure
DRUGD-PLEX
D-PLEX is reconstituted into paste and administered in a single application following closure of the fascia, on the fascia suture line, and on the soft tissues of the abdominal wall along the whole length of the surgical wound (including muscle, fat and dermis).
Sponsors
PolyPid Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Masking description
Subject will be blinded to the treatment arm assignment. Physicians which were not part of the team in the surgery room, or from the hospital's infectious diseases dept. will remain blinded to the study arm, and will be those assessing the incisional wound for the study primary endpoint at each follow-up visit post the index surgery. On top, for each suspicion of infection, an external, independent and blinded adjudication committee will be the one making the final decision whether an infection occured or not.
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. Subjects will be randomized to either the investigational arm (SOC + D-PLEX) or to the control arm (SOC only) in a 1:1 ratio. Subjects will be blinded to the study arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects undergoing elective abdominal colon surgery involving resection and ileocolonic, ileorectal, colocolonic or colorectal anastomosis or with a stoma, who are preoperative stable hemodynamically. In a laparoscopic surgery, an abdominal wall incision ≥ 5 cm should be involved. 2. Male or non-pregnant female. 3. Females of childbearing potential should have a negative serum pregnancy test prior to index procedure. All females of childbearing potential must agree to use a highly effective method of contraception (e.g., double barrier, oral or parenteral hormonal, intrauterine device, or spermicide) consistently and correctly for the duration of the study. 4. Age ≥ 18 years old at screening. 5. Subjects who signed a written informed consent. 6. Willing and able to participate and meet all study requirements. 7. Survival expectancy of at least 60 days post randomization.
Exclusion criteria
1. Subjects scheduled for abdominal surgery which is classified as emergency. 2. Subjects with any preoperative active infection that is currently being treated with antibiotics. 3. Subjects receiving any antibiotic therapy in the past 4 weeks prior to enrollment other than prophylaxis or antibiotic for the treatment of the disease for which the surgery is indicated. 4. Subjects undergoing concomitant additional procedures other than colon resection surgery (e.g., hyper-thermic intraperitoneal chemotherapy, liver resection, etc.). Female sterilization surgery (e.g., salpingo-oophorectomy, hysterectomy, etc.), involvement of a small bowel procedure, or cholecystectomy may be allowed, pending an advanced consultation and approval from the sponsor. 5. Subject received chemotherapy within the past 4 weeks of surgery, or radiation for colorectal cancer to the abdominal area, prior to the planned abdominal surgery (neo-adjuvant treatment). 6. Subjects that received oral or IV doxycycline during the past 4 weeks prior to screening. 7. Subjects with known hypersensitivity to doxycycline and/or to the tetracycline family of drugs or to the D-PLEX excipients. 8. Subjects with known allergies to more than 3 substances (as determined from allergy questionnaire at screening). 9. Subjects with history of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intravenous steroids/intramuscular epinephrine or in the opinion of the investigator the subject is at high risk of developing severe allergic/hypersensitivity reactions. 10. Subjects with uncontrolled asthma (GINA III-IV). 11. Subjects with End Stage Renal Disease (ESRD/CKD stage 5). 12. Subjects with chronic urticaria. 13. Subjects diagnosed with TIA/CVA/ACS within the past 1 year prior to randomization. 14. Subjects that have undergone any prior abdominal surgery and current planned surgery involves re-opening the scar of the prior abdominal surgery. 15. Any subject with an active malignancy or malignancy that has not been in complete remission for at least 5 years. Excluding: * Subjects with potentially resectable non-metastatic colorectal cancer for which the surgery is indicated. * Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma of the skin, and basal cell carcinoma of the skin. * Subjects with non-violent cancer that does not require treatment 4 weeks prior to, and throughout the entire study duration. 16. Subjects with other concurrent severe and/or uncontrolled medical condition that could compromise participation in the study (e.g., non-GI active infection, uncontrolled diabetes, uncontrolled hypertension, congestive heart failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, uncompensated cirrhosis, active upper GI tract ulceration). 17. Psychiatric, addictive, or any other disorder that compromises ability to provide informed consent for participation in this study. 18. Chronic alcohol or drug abuse. 19. Pregnant or breast-feeding women or women of childbearing age who refuse or are prohibited from using an effective contraceptive method of birth control (e.g., double barrier, oral or parenteral hormonal, intrauterine device, or spermicide) throughout study participation including the safety follow-up period. 20. Subjects that received any investigational drug within 30 days or 5½ half-lives of enrollment in the study (whichever is longer). 21. Subjects participating in any other interventional studies. 22. Any subject who, in the opinion of the investigator, is not eligible to participate in the study and/or comply with protocol requirements (e.g., due to a cognitive or medical condition).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Combined Infection and Mortality Rate Within 30 Days Post Index Surgery | 30 days post surgery | The infection rate and mortality rate were measured by the number and proportion of subjects with either an SSI event (as determined by the blinded and independent adjudication committee, within 30 days post abdominal surgery) or mortality for any reason within 30 days post index surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average ASEPSIS Assessment Score (for Parameters Additional Treatment, Serous Discharge, Erythema, Purulent Exudate, Separation of Deep Tissue, Isolation of Bacteria, Stay Duration as Inpatient) During 30 Days Post-surgery. | 30 days post surgery | ASEPSIS is acronym of wound assessment and treatment parameters (described in the title), which provides numerically score during an inspection of the surgical site. The final score is being interpreted to severity of wound appearance and the clinical consequences of the infection. Each parameter will be evaluated and numerically scored. Some (Serous discharge \& Erythema) will be marked between 0 - 5 and others (Purulent exudate \& Separation of deep tissue) are marked between 0 - 10 - based on the proportion of the wound they affect when 0 is none and either 5 or 10 are for over 80% of the wound. Other parameters (Additional antibiotic treatment, a requirement for pus drainage, isolation of bacteria \& stay duration as an inpatient) are scored Yes or No. No equals 0. Yes is calculated as either 5 points (for some parameters) or 10 for others. The final score can be in the range of 0 - 70. 0 - 10 for wound which heals satisfactorily and over 40 for a severe wound infection. |
| Mortality Rate Within 30 Days Post Abdominal Surgery | 30 days post surgery | Death from any reason within 30 days post abdominal surgery |
Countries
Israel
Contacts
STUDY_CHAIRShmuel Sharoni, MD
Medical Director
Participant flow
Recruitment details
Subjects who met the eligibility requirements were randomized to either the investigational arm (SOC + D-PLEX) or the control arm (SOC only) in a 1:1 ratio. Subjects were randomized through an interactive web randomization system (IWRS) integrated with the electronic Case Report Form (eCRF), based on the subject's information collected during the screening period and details of the planned surgery.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 15.74 |
| BMI | 27.47 kg/m^2 STANDARD_DEVIATION 5.27 |
| Height | 170.24 cm STANDARD_DEVIATION 9.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 99 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 61 Participants |
| Weight | 77.91 kg STANDARD_DEVIATION 17.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 100 | 0 / 101 |
| other Total, other adverse events | 52 / 100 | 50 / 99 |
| serious Total, serious adverse events | 20 / 100 | 16 / 99 |
Outcome results
None listed