Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery (Triple IN)
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.
Drug: E-101 Solution 300 GU/ml
Drug: Saline solution
|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)|
- 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.)
- 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.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
|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).
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.)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01297959
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|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|