Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery (Triple IN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Excited States, LLC
Sponsor:
Collaborators:
Veristat, Inc.
Biotec Services International Ltd
Eurofins Medinet
CBR International Corp.
Information provided by (Responsible Party):
Excited States, LLC
ClinicalTrials.gov Identifier:
NCT01297959
First received: February 11, 2011
Last updated: November 20, 2014
Last verified: November 2014
  Purpose

This study is intended to determine the efficacy 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.


Condition Intervention Phase
Infections
Drug: E-101 Solution 300 GU/ml
Drug: Saline solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 3 Study of the Efficacy and Safety of Topical E-101 Solution to Prevent Incisional Infections Among Colorectal Surgery Patients (Triple IN Study-INhibition of INcisional INfections)

Further study details as provided by Excited States, LLC:

Primary Outcome Measures:
  • The incidence of superficial (skin and subcutaneous tissues) and deep (muscle and/or fascia) incisional surgical site infections (SSI) involving the primary open-laparotomy incision. [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]
    Incisional SSI (both superficial and deep) will be diagnosed by a blinded assessor using a modification of the original SSI definition proposed by the the US Centers for Disease Control (Horan, Andrus and Dudeck. 2008. Am. J. Infect. Cont.)


Secondary Outcome Measures:
  • Mean CIWS (Clinical Infection Wound Score) [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]

    Wounds will be assigned a whole integer value on a scale from 0 to 5 based on the severity of signs and symptoms associated with infection (e.g., wound erythema, spontaneous wound dehiscence) by a blinded assessor where a score of 0 is normal post-operative wound appearance and a score of 5 indicates infection of the primary incision involving deep incisional structures manifested by one or more of the following:

    • spontaneous partial or complete wound dehiscence with erythema and/or pain
    • spontaneous purulent drainage
    • a wound abscess
    • clinical or histological evidence of fasciitis or myonecrosis

  • Proportion of subjects with incidence of incisional SSI, accompanied by findings of purulent drainage, wound abscess, or positive microbial culture from one or more incisional samples [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]
  • Proportion of subjects with incidence of superficial and deep incisional SSI [ Time Frame: 14 days post-surgery ] [ Designated as safety issue: No ]
  • Quality of life scores based on the EQ-5D-3L questionnaire obtained via interview of the subject by qualified study site personnel [ Time Frame: At Screening, 7, 14, and 30 days post-surgery ] [ Designated as safety issue: No ]
    This evaluation will only be performed for English-speaking subjects at US sites.

  • Proportion of subjects re-hospitalized for SSI. [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]
  • Proportion of subjects with each wound healing score by a blinded assessor on a standardized quantitative scale (termed Clinical Wound Healing Score [CWHS]) [ Time Frame: 3, 5, 7, 14, and 30 days post-surgery ] [ Designated as safety issue: Yes ]

    The points on the CWHS scale are the following:

    • 0 = normal, intact incision without any spontaneous wound dehiscence
    • 1 = spontaneous wound dehiscence that extends < 2 cm along primary incision in the absence of erythema and/or pain
    • 2 = spontaneous wound dehiscence that extends ≥ 2 cm along primary incision in the absence of erythema and/or pain

  • Wound pain score assessments [ Time Frame: 3, 5, 7, 14, and 30 days post-surgery ] [ Designated as safety issue: Yes ]
    Wound pain assessment will be based on a categorical scale ranging from 0 to 10, where 0 is no pain and 10 is unimaginable, unspeakable pain. The worst assessment over all days will be summarized by treatment group whereby the number and percent of subjects whose worst pain assessment is 0, 1, 2, 3...10 will be presented.

  • Incidence of detectable, induced antibodies to components of E-101 Solution [ Time Frame: Up to 6 months post-surgery ] [ Designated as safety issue: Yes ]
    Serum samples collected 14 days and 30 days after surgery will be screened for antibodies to components of E-101 solution as compared to results from pre-treatment samples. For any subject in which there is detectable, induced antibodies by ELISA, the serum samples will be screened for neutralization. Subjects who have detectable induced antibodies 30 days after surgery will be asked to provide an additional sample 3 months after surgery, and again at 6 months after surgery if induced antibodies are still detectable at the 3 month visit

  • Independent Adjudication Committee Review [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]
    As a sensitivity analysis, an independent, blinded adjudication committee will be convened to review all cases of SSI with CIWS scores of 1, 2, or 3 that lack positive microbiological findings). The independent adjudication committee will score cases as likely or unlikely SSI, based on review of photographs of the primary incision and on key study data collected prior to the SSI diagnosis.

  • Incidence of perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA)-associated vasculitis [ Time Frame: 30 days, 6 months ] [ Designated as safety issue: Yes ]
    A subset of 300 subjects (150 subjects from each study arm) at selected study sites will be evaluated for p-ANCA-associated vasculitis. Incidence of p-ANCA-associated vasculitis will be determined by ELISA screening for induced antibodies to human myeloperoxidase, serum anti-nuclear antigen test detected by immunofluorescent microscopy (IFM), serum complement 3 [C3], serum complement 4 [C4], complete blood count, urinalysis (microscopic and chemistry), coagulation tests, serum chemistries, and physical examinations for vasculitis symptoms.


Estimated Enrollment: 1350
Study Start Date: August 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E-101 Solution 300 GU/mL Drug: E-101 Solution 300 GU/ml
8 mL of E-101 Solution at a pMPO concentration of 300 GU/ml applied topically twice to surgical wound site (just after incision without penetration of the rectus fascia or linea alba and just prior to skin closure after closure of rectus fascia or linea alba).
Placebo Comparator: Saline solution Drug: Saline solution
8 mL of Placebo topically twice to surgical wound site (just after incision without penetration of the peritoneal fascia and just prior to skin closure).

Detailed Description:

The purpose of this standard-of-care, pivotal Phase 3 study is to evaluate the efficacy and safety of topical E-101 Solution after direct application into the principal surgical incision in the prevention of superficial and deep incisional surgical site infections (SSI) within 30 days after elective colorectal surgery. The study is intended to support a target indication statement of: "E-101 Solution is indicated for the prophylaxis of incisional surgical site infections following elective colorectal surgery". E-101 Solution is comprised of the active ingredients of glucose oxidase (GO) and porcine myeloperoxidase (pMPO) that produce coupled reactions after the addition of glucose substrate. The hypothesis is that E-101 Solution topically applied directly into the principal incision is safe and significantly reduces the incidence of incisional SSI compared to placebo topical application. (The principal surgical incision is ≥ 5cm and < 35 cm used as a hand port, colorectal specimen extraction port, or extracorporeal manipulation port depending on the specific colorectal surgical approach.)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. Male or female ≥18 years of age.
  4. If female, is non-pregnant (negative pregnancy test result at the Screening/Randomization Visit) and non-lactating.
  5. 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., pANCA), as well as patients 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 subject 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. 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. Patients 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 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 patient 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. Patients with severe COPD that are likely to need > 24 hours postoperative ventilator support (e.g., patients 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 subject would likely be unable to maintain adequate care of the principal incision post-operatively.
  26. Anticipate that patient will not be available for study visits/ procedures or if in the opinion of Investigator there is concern that patient 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01297959

Contacts
Contact: Barbara Tobichuk +1-508-589-4998 btobichuk@exoxemis.com
Contact: Donna Moran +1-508-589-6018 dmoran@exoxemis.com

  Show 29 Study Locations
Sponsors and Collaborators
Excited States, LLC
Veristat, Inc.
Biotec Services International Ltd
Eurofins Medinet
CBR International Corp.
Investigators
Study Director: Peter O'Hanley, PhD, MD, MPH Excited States, LLC
Study Chair: Robert Martindale, MD, PhD Oregon Health and Science University
Principal Investigator: Michael J Stamos, MD University of California, Irvine
Principal Investigator: Jerrold H Levy, MD Emory Healthcare
  More Information

No publications provided

Responsible Party: Excited States, LLC
ClinicalTrials.gov Identifier: NCT01297959     History of Changes
Other Study ID Numbers: E-101:PH3:2012:004
Study First Received: February 11, 2011
Last Updated: November 20, 2014
Health Authority: Israel: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Excited States, LLC:
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

Additional relevant MeSH terms:
Communicable Diseases
Infection
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014