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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 October 2013 by Excited States, LLC
TFS Trial Form Support
Veristat, Inc.
Biotec Services International Ltd
Eurofins Medinet
CBR International Corp.
Information provided by (Responsible Party):
Excited States, LLC Identifier:
First received: February 11, 2011
Last updated: October 24, 2013
Last verified: October 2013

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
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: November 2014
Estimated Primary Completion Date: May 2014 (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:

This standard-of-care pivotal Phase 3 study with a blinded assessor to determine wound healing and incisional infection by standardized criteria is designed to evaluate the efficacy and safety of topical application of E-101 Solution directly into surgical wounds for the prevention of superficial and deep incisional surgical site infections (SSI) within 30 days after elective colorectal surgery. E-101 Solution is comprised of glucose oxidase (GO) and porcine myeloperoxidase (p-MPO), as the active ingredients, that produce coupled reactions after the addition of substrate. The hypothesis is that E-101 Solution, topically applied into the surgical incision, significantly reduces the incidence of incisional SSI and is safe compared to saline topical application. An independent Data Safety Monitoring Board (DSMB) will review all cases as an additional oversight to protect the safety of subjects.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Scheduled to undergo elective colon and/or rectal surgical procedures involving an open laparotomy incision of 7 cm in length or greater but no more than 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:

    1. Oral, implantable, or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit.
    2. Intrauterine device.
    3. Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream).
    4. Not be sexually-active.
  6. 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 (e.g., patients with idiopathic necrotizing glomerulonephritis and certain systemic vasculitis conditions [e.g., microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss Syndrome]).
  3. Use of microbial sealant (IntegusealTM) to close the primary surgical incisional wound or any suture that has not been formally approved by the relevant local national regulatory agency.
  4. Absolute contraindication to general anesthesia.
  5. Hypersensitivity reactions to steri-strip tapes, medical-surgery tapes, adhesives, or sutures.
  6. History of hypertrophic scarring after surgery or keloid formation after skin abrasions/cuts.
  7. Subjects diagnosed with collagen vascular disease, including scleroderma.
  8. Body mass index [BMI] >40.
  9. ASA score >3.
  10. Undergoing emergent surgery with any clinical signs of peritonitis and emergency surgery (urgent surgery is allowed if informed consent is obtained and assessment for the study can be performed). Emergency surgery includes cases where standard bowel preparation and other preoperative assessments cannot be performed.
  11. 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).
  12. Evidence, preoperatively, of any of the following: sepsis, severe sepsis, or septic shock (note that Systemic Inflammatory Response Syndrome [SIRS], alone, is not an exclusion criterion).
  13. Preoperative severe neutropenia (total neutrophil count ≤500 EE 6/L).
  14. Current abdominal wall infection/surgical site infection secondary to previous laparotomy/laparoscopy or from any other cause.
  15. Receiving any oral or intravenous antibiotics within 1 week prior to the date of planned procedure. Prophylactic antibiotics for dental or other brief procedures are acceptable.
  16. Preoperative evaluation suggests intra-abdominal process that might preclude full closure of the skin.
  17. History of chemotherapy within prior 2 weeks or radiation therapy within prior 6 weeks.
  18. History of major organ transplantation, including bone marrow transplantation.
  19. History of laparotomy within 60 days prior to planned procedure.
  20. Planning to undergo a second laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 60 days of planned procedure.
  21. Preoperative prothrombin time or INR > 2 x upper limit of normal.
  22. Taking systemic steroids >20 mg prednisone daily, infliximab (RemicadeR), or other anti-inflammatory/immunosuppressive medication within 2 weeks prior to surgery or a history of a current immunosuppressive condition (e.g., symptomatic HIV infection), defined as a CD4 count < 200.
  23. Postsurgical life expectancy ≤ 60 days (in the Study Site Investigator's or sponsor's opinion).
  24. Refusal to accept medically indicated blood products.
  25. Any patient in which the planned surgery would include: i) placement of a stoma in the primary incision; ii) incision through an anterior abdominal wall mesh and this mesh will not entirely be removed during the planned procedure; iii) placement of a drain into the supra-peritoneal fascia space of the primary incision; and iv) placement of a drain into the intraperitoneal space that emerges through primary surgical incision. (Note: If, however, an intraperitoneal drain emerges outside of the primary incision, this is allowed.)
  26. Presence of prosthetic cardiac valve(s).
  27. Patients with severe COPD that are likely to need >24 hours postoperative ventilator support (e.g., patients on chronic supplemental oxygen or an estimated forced expiratory volume in 1 second [FEV 1] less than 50% of expected based on bedside spirometry).
  28. Patients with pre-operative bacteriuria of ≥ 1 EE 4 bacteria/ml urine and/or positive leucocyte esterase and/or nitrite urine dipstick tests.
  29. Patients with a condition (e.g., nail infections, sinusitis, dental infections, vaginitis/vaginosis, chronic bronchitis) requiring frequent or chronic administration of antimicrobials (received antimicrobials at least twice for ≥ 2 weeks during past 6 months).
  30. If in the opinion of the Study Site Investigator, the potential subject would or might be unable to maintain adequate care of the incision post-operatively.
  31. Anticipated non-availability for study visits/procedures.
  32. Age below 18 years.
  33. History of any illicit drug usage within the prior year or current history of alcohol abuse or alcoholism.
  34. Lack of willingness to have personal study related data collected, archived, or transmitted under blinded condition to regulatory agencies.
  35. 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 identifier: NCT01297959

Contact: Laura Cedergren +1 610-994-9252
Contact: Mary M Byrnes, RN, BSN +1 908-806-5990

  Hide Study Locations
United States, Alabama
University of South Alabama Medical Center Recruiting
Mobile, Alabama, United States, 36617
Principal Investigator: Paul Rider, MD         
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Principal Investigator: Kyle Cologne, MD         
Stanford University Medical Center / Stanford Cancer Center Recruiting
Stanford, California, United States, 94305
Principal Investigator: Mark Welton, MD         
United States, Florida
Sheridan Clinical Research Recruiting
Sunrise, Florida, United States, 33323
Principal Investigator: Juan Restrepo, MD         
University of South Florida/Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Principal Investigator: Jorge Marcet, MD         
Cleveland Clinic Florida Recruiting
Weston, Florida, United States, 33331
Principal Investigator: Steven Wexner, MD         
United States, Illinois
John H. Stroger, Jr. Hospital of Cook County Recruiting
Chicago, Illinois, United States, 60612
Principal Investigator: Jennifer Blumetti, MD         
United States, Indiana
Indiana University Not yet recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Virgilio George, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Principal Investigator: Susan Galandiuk, MD         
United States, Louisiana
Ochsner Clinic Foundation / Colon and Rectal Surgery Recruiting
New Orleans, Louisiana, United States, 70121
Principal Investigator: David Margolin, MD         
United States, Massachusetts
Berkshire Medical Center, Inc Recruiting
Pittsfield, Massachusetts, United States, 01201
Principal Investigator: Timothy Counihan, MD         
United States, Michigan
Henry Ford Hospital / Colon and Rectal Surgery Recruiting
Detroit, Michigan, United States, 48202
Principal Investigator: Eric Szilagy, MD         
United States, Missouri
Washington University School of Medicine Not yet recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Matthew Mutch, MD         
United States, Nebraska
Colon and Rectal Surgery, Inc. Not yet recruiting
Omaha, Nebraska, United States, 68114
Principal Investigator: Charles A. Ternent, MD         
United States, New Jersey
Central State Medical Recruiting
Freehold, New Jersey, United States, 07728
Principal Investigator: Amit Kharod, MD         
Saint Barnabas Medical Center Recruiting
Livingston, New Jersey, United States, 07039
Principal Investigator: Ronald S. Chamberlain, MD         
Meridian Health Jersey Shore University Medical Center Recruiting
Neptune, New Jersey, United States, 07753
Principal Investigator: Glenn Parker, MD         
United States, New York
Albany Medical Center Recruiting
Albany, New York, United States, 12208
Principal Investigator: Edward Lee, MD         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Principal Investigator: Arnold Berlin, MD         
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Principal Investigator: Joel Bauer, MD         
Stony Brook University Medical Center Recruiting
Stony Brook, New York, United States, 11794
Principal Investigator: Roberto Bergamaschi, MD, PhD         
SUNY Upstate Medical University Not yet recruiting
Syracuse, New York, United States, 13210
Principal Investigator: Jeri Bem, MD         
United States, Ohio
Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Principal Investigator: Janice Rafferty, MD         
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States, 97239
Principal Investigator: Robert Martindale, MD, PhD         
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Principal Investigator: Warren Lichliter, MD         
Southwest Surgical Associates, L.L.P. Recruiting
Houston, Texas, United States, 77074
Principal Investigator: Michael T Wood, M.D.         
Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Randolph H. Bailey, MD         
Methodist Hospital Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Jaime Mayoral, MD         
Southwest Surgical Associates, LLP Recruiting
Sugarland, Texas, United States, 77479
Principal Investigator: Guillermo Ponce DeLeon, MD         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Principal Investigator: Alessandro Fichera, MD         
Rambam Medical Center Recruiting
Haifa, Israel
Principal Investigator: Simon Daniel Duek, MD         
Hadassah Medical Center Recruiting
Jerusalem, Israel
Principal Investigator: Avi Rivkind, MD         
Rabin Medical Center, Beilinson Hospital Recruiting
Petah Tikva, Israel
Principal Investigator: Nir Wasserberg, MD         
The Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel
Principal Investigator: Hagit Tulchinsky, MD         
The Chaim Sheba Medical Center Recruiting
Tel Hashomer, Israel
Principal Investigator: Oded Zmora, MD         
Sponsors and Collaborators
Excited States, LLC
TFS Trial Form Support
Veristat, Inc.
Biotec Services International Ltd
Eurofins Medinet
CBR International Corp.
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 Identifier: NCT01297959     History of Changes
Other Study ID Numbers: E-101:PH3:2012:004
Study First Received: February 11, 2011
Last Updated: October 24, 2013
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
Glucose Oxidase
Colorectal surgery
Incisional Surgical Site Infections (SSI)
Anti-infective Agents, Local
Clinical Trial, Phase III

Additional relevant MeSH terms:
Communicable Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses processed this record on October 29, 2014