Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery
Condition: Infections
MeSH terms: Infections; Communicable Diseases
Intervention: E-101 Solution 300 GU/ml; Saline solution
Intervention description: 8 mL of E-101 Solution; Saline solution matched to E-101
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 503.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Surgical Wound Infection; Therapeutic Enzyme System; Singlet Oxygen; Peroxidase; Glucose Oxidase; Colorectal surgery; Incisional Surgical Site Infections (SSI); Anti-infective Agents, Local; Clinical Trial, Phase III

Summary:

      This study is intended to determine the efficacy, safety and tolerability of topical
      application of E-101 Solution directly into the surgical incisional wound in the prevention
      of infection of superficial and deep surgical incisional wounds. E-101 Solution is an
      enzyme-based antiseptic that is being developed for direct application to a surgical
      incision.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Scheduled to undergo elective colon and/or rectal surgical procedures involving open
             laparotomy, hand-assisted laparoscopy, and laparoscopic-assisted approaches. The
             principal incision must have a length of > 5 cm and < 35 cm in length. Eligible
             surgeries are: left hemicolectomy, right hemicolectomy, transverse colectomy,
             ileocolic resection, total abdominal colectomy with ileorectal anastomosis, total
             abdominal proctocolectomy (portion of specimen to be extracted via laparotomy), low
             anterior resection, sigmoid resection, non-emergent Hartmann procedure, colostomy
             takedown through laparotomy (not peristomal) incision, ileo-pouch anal anastomosis,
             and abdominal perineal resection of the rectum.

          2. Able to give informed consent.

          3. If female, is non-pregnant (negative pregnancy test result at the
             Screening/Randomization Visit) and non-lactating.

          4. If female, is either not of childbearing potential (defined as postmenopausal for at
             least 1 year or surgically sterile [status post bilateral tubal occlusion, bilateral
             oophorectomy, or hysterectomy]) or practicing 1 of the following methods of birth
             control and agrees to continue with this regimen over the study surveillance period:

               -  Oral, implantable, or injectable contraceptives for 3 consecutive months before
                  the Baseline/Randomization Visit

               -  Intrauterine device

               -  Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or
                  cream)

               -  Not sexually-active. Agreement to be available for evaluation at the study site
                  for scheduled visits.

        Exclusion Criteria:

          1. Hypersensitivity to porcine products.

          2. History of known anti-myeloperoxidase autoantibodies (i.e., perinuclear
             anti-neutrophil cytoplasmic antibody [pANCA]), as well as participants with known
             idiopathic necrotizing glomerulonephritis and certain systemic vasculitis conditions
             [e.g., microscopic polyangiitis of small blood vessels, Wegener's granulomatosis, and
             Churg-Strauss Syndrome]).

          3. Use of microbial sealant (IntegusealTM), any antibiotic-embedded suture, or any
             antimicrobial-embedded suture to close the principal incision or any suture in the
             surgical field that has not been formally approved by the relevant local national
             regulatory authority.

          4. Absolute contraindication to general anesthesia.

          5. Hypersensitivity reactions to steri-strip tapes, medical-surgery tapes, adhesives, or
             sutures. (Note: If there can be assurances that the participant will not be exposed to
             these materials that cause hypersensitivity, alternatives will be allowed.)

          6. History of keloid or hypertrophic scarring within or near an incision from a prior
             surgery.

          7. Body mass index [BMI]: > 50 or < 20 (both due to the extremely high risk of poor wound
             healing).

          8. American Society of Anesthesiologists (ASA) Score > 3.

          9. Undergoing emergency colorectal surgery such that standard bowel preparation and other
             standard preoperative precautions and assessments cannot be performed in time before
             the index-surgery.

         10. The planned index-surgery involves removal or placement of mesh (either synthetic or
             biological) as part of closure in the principal incision or traversing any part of a
             pre-existing mesh (either synthetic or biological) in the principal incision.

         11. There are clinical signs of overt infection necessitating systemic antibiotics via
             oral, intramuscular, or intravenous routes (e.g., infection of the abdominal wall,
             peritonitis, pneumonia, and sepsis/septic shock) prior to the index-surgery.

         12. Preoperative severe neutropenia (total neutrophil count ≤500 X 109/L). (Note: Testing
             should be performed at the local laboratory.)

         13. Receiving any oral or intravenous antibiotics within 24 hours prior to the
             index-surgery. (Note: It is permissible to administer conventional oral prophylactic
             antibiotics as bowel preparation up to the time of the index- surgical procedure, as
             well as intravenous or intramuscular prophylactic antibiotics just prior to the
             index-surgery as per the treating surgeon's standard of care.)

         14. Preoperative evaluation that the intra-abdominal process might preclude full closure
             of the skin incision due to severe or morbid obesity (i.e., any mechanical reason that
             would prevent/preclude primary intent wound healing) at the principal incision.

         15. History of major organ transplantation (e.g., lung, liver, or kidney), including bone
             marrow transplantation, or intent to perform major organ transplant as a concomitant
             surgery.

         16. History of a complicated laparotomy within 30 days prior to planned index-surgery.

         17. Planning to undergo a second colorectal surgical procedure (e.g., colostomy or
             ileostomy takedown) or any other general surgery in less than 30 days of
             index-surgery.

         18. Likely preoperative urinary tract infection, as evident by: i) symptoms of upper
             urinary tract infection (e.g., fever and/or flank pain) or ii) symptoms of lower
             urinary tract infection (e.g., urinary frequency, dysuria, urgency, and/or suprapubic
             pain); accompanied by any one of the following: 1) bacteriuria of ≥104 bacteria/mL
             urine or 2) positive urine leucocyte esterase or positive nitrite urine dipstick
             tests. Also exclude any man under age 60 years who has both positive urine nitrite and
             leucocyte esterase dipstick tests - even if he is asymptomatic (unless he has
             predisposing factors for urinary tract infection - e.g., spinal cord injury). (Note:
             Testing should be performed at the local laboratory.)

         19. Undergoing a significant concomitant surgical procedure (e.g., hysterectomy) or any
             mesh repair (either synthetic or biological mesh) as part of closure. The following
             concomitant procedures are allowed: appendectomy, cholecystectomy, oophorectomy,
             removal of Meckel's diverticulum, primary repair of small ventral hernia (i.e., <30
             cm2), liver biopsy/wedge resection (but not liver resection).

         20. Participants with a condition (e.g., recurrent urinary tract infections, nail
             infections, sinusitis, dental infections, vaginitis/vaginosis, or chronic bronchitis)
             requiring frequent or chronic administration of antimicrobials (received
             antibiotics/antimicrobials at least twice for ≥ 2 weeks during past 6 months).

         21. Preoperative prothrombin time or international normalized ratio (INR) > 2 x upper
             limit of normal. (Note: Testing should be performed at the local laboratory.)

         22. Postsurgical life expectancy ≤ 60 days (in the Investigator's or Sponsor's opinion).

         23. Any participant in which the planned surgery would include: i) placement of a stoma in
             the principal incision; ii) placement of a drain into the supra-peritoneal fascia
             space that emerges through the principal incision; iii) placement of a drain into the
             intraperitoneal space that emerges through the principal incision; and iv)
             supplementation of any of the irrigation fluid with antibiotic or antiseptic drugs.

         24. Participant with severe Chronic obstructive pulmonary disease (COPD) that are likely
             to need > 24 hours postoperative ventilator support (e.g. participant on chronic or
             intermittent supplemental oxygen or an estimated forced expiratory volume in 1 second
             (FEV1) less than 50% of expected based on bedside spirometry).

         25. If, in the opinion of Investigator, the potential participant would likely be unable
             to maintain adequate care of the principal incision post-operatively.

         26. Anticipate that participant will not be available for study visits/ procedures or if
             in the opinion of Investigator there is concern that participant might not comply with
             study visits/procedures (e.g., due to ongoing illicit drug usage or alcohol abuse).

         27. Lack of willingness to have personal study-related data collected, archived, or
             transmitted under a blinded condition to regulatory agencies.

         28. Participation within 30 days before the start of this study in any experimental drug
             or device study; or currently participating in a study in which the administration of
             investigational drug or device within 60 days is anticipated.