Trial record 1 of 3 for:    E-101
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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
Sponsor:
Collaborators:
TFS Trial Form Support
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: October 24, 2013
Last verified: October 2013

February 11, 2011
October 24, 2013
August 2012
May 2014   (final data collection date for primary outcome measure)
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.)
Comparison of incidence (percentage of patients) of superficial and deep incisional surgical site infections (SSI) across treatment groups, as diagnosed by the surgeon or attending physician [ Time Frame: 45 days post-surgery ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01297959 on ClinicalTrials.gov Archive Site
  • 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.
  • Effect on quality of life [ Time Frame: 45 days post-surgery ] [ Designated as safety issue: No ]
  • Comparison by treatment group of post-exposure perinuclear anti-neutrophil cytoplasmic antibody (pANCA) incidence, as determined by increases in anti-human MPO antibody and/or incidence of a clinical syndrome compatible with on-going systemic vasculitis [ Time Frame: 6 months post-surgery ] [ Designated as safety issue: Yes ]
    Serum samples will be tested for titer of antibody to human myeloperoxidase (hMPO) using an ELISA. Sera with a significant increase in hMPO titer following exposure to study drug will be assessed to be positive for pANCA if the hMPO ELISA results are confirmed with an IIF test. Patients who are serologically positive, or who experience a clinical syndrome compatible with ongoing systemic vasculitis, will be considered to be pANCA-positive for purposes of this outcome assessment
Not Provided
Not Provided
 
Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery
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)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Prevention
Infections
  • 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).
  • 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).
  • Experimental: E-101 Solution 300 GU/mL
    Intervention: Drug: E-101 Solution 300 GU/ml
  • Placebo Comparator: Saline solution
    Intervention: Drug: Saline solution
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1350
November 2014
May 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Laura Cedergren +1 610-994-9252 laura.cedergren@tfscro.com
Contact: Mary M Byrnes, RN, BSN +1 908-806-5990 mary.byrnes@tfscro.com
United States,   Israel
 
NCT01297959
E-101:PH3:2012:004
Yes
Excited States, LLC
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
Excited States, LLC
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP