Study to Evaluate Efficacy and Safety of E-101 Solution for Preventing Surgical Site Infections After Colorectal Surgery

NCT01297959 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: E-101:PH3:2012:004
• Study Type: interventional
• Target: 503
• Locations: 2 countries
• Sites: 39

Brief 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.

Conditions

Infections

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants In Intent to Treat (ITT) Analysis Set With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving Principal Incision Within 30 Days After Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively

  Superficial SSI: purulent drainage (PD) from superficial incision (SI), organisms isolated from aseptically obtained culture fluid from SI, pain/tenderness, localized swelling, redness, or heat extending from principal incision (PI), or PI deliberately opened by surgeon for presumptive PI infection and was culture-positive, a negative wound culture but clinical evidence of infection on Clinical Infection Wound Scale (CIWS). Deep incisional SSI: PD from deep incision (DI) but not from organ/space component of the surgical site, fever (\>38°C), localized wound pain, or wound tenderness, or DI spontaneously dehisces and/or deliberately opened by surgeon, and microbiological culture of DI by aseptic collection or deep wound swab was positive, an abscess or other evidence of infection involving DI was found on direct examination, during reoperation, or by histopathological or radiological examination, negative deep wound culture but clinical evidence of deep wound infection on CIWS.

  Surgery (Day 0) up to 30 days post-surgery

• Number of Participants In Per-Protocol (PP) Analysis Set With Superficial and Deep Incisional SSI Involving Principal Incision Within 30 Days After the Index-surgery as Determined by Blinded Assessors 30 Days Post-operatively

  Superficial SSI: PD from SI, organisms isolated from aseptically obtained culture fluid from SI, pain/tenderness, localized swelling, redness, or heat extending from PI, or PI deliberately opened by surgeon for presumptive PI infection and was culture-positive, a negative wound culture but clinical evidence of infection on CIWS. Deep incisional SSI: PD from DI but not from organ/space component of the surgical site, fever (\>38°C), localized wound pain, or wound tenderness, or DI spontaneously dehisces and/or deliberately opened by surgeon, and microbiological culture of DI by aseptic collection or deep wound swab was positive, an abscess or other evidence of infection involving DI was found on direct examination, during reoperation, or by histopathological or radiological examination, negative deep wound culture but clinical evidence of deep wound infection on CIWS.

  Surgery (Day 0) up to 30 days post-surgery

Secondary Outcomes (18)

• Mean Clinical Infection Wound Scale Score (CIWS)

  Surgery (Day 0) up to 30 days post-surgery

• Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)

  Surgery (Day 0) up to 30 days post-surgery

• Number of Participants With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving the Principal Incision (PI) Within 30 Days After the Index-surgery as Determined by Blinded Assessors 14 Days Post-operatively

  Surgery (Day 0) up to 14 days post-surgery

• Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire

  Day 0 up to Day 30

• Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire

  Day 0 up to Day 30

Other Outcomes (2)

• Minimum Inhibitory Concentration (MIC) at 90%

  Surgery (Day 0) up to to 30 days post surgery

• Minimum Bactericidal Concentration (MBC) at 90%

  Surgery (Day 0) up to to 30 days post surgery

Study Arms (2)

E-101 Solution 300 GU/mL

EXPERIMENTAL

Participants will receive E-101 Solution at porcine myeloperoxidase (pMPO) concentration of 300 guaiacol units per milliliter (GU/mL) applied topically twice to surgical wound site. The first topical application will occur just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application will occur just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.

Drug: E-101 Solution 300 GU/ml

Placebo (Saline solution)

PLACEBO COMPARATOR

Participants will receive placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application will occur just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application will occur just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.

Drug: Saline solution

Interventions

E-101 Solution 300 GU/ml DRUG

8 mL of E-101 Solution

E-101 Solution 300 GU/mL

Saline solution DRUG

Saline solution matched to E-101

Placebo (Saline solution)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Able to give informed consent.
• If female, is non-pregnant (negative pregnancy test result at the Screening/Randomization Visit) and non-lactating.
• 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.

You may not qualify if:

• Hypersensitivity to porcine products.
• 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 \[e.g., microscopic polyangiitis of small blood vessels, Wegener's granulomatosis, and Churg-Strauss Syndrome\]).
• 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.
• Absolute contraindication to general anesthesia.
• 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.)
• History of keloid or hypertrophic scarring within or near an incision from a prior surgery.
• Body mass index \[BMI\]: \> 50 or \< 20 (both due to the extremely high risk of poor wound healing).
• American Society of Anesthesiologists (ASA) Score \> 3.
• 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.
• 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.
• 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.
• Preoperative severe neutropenia (total neutrophil count ≤500 X 109/L). (Note: Testing should be performed at the local laboratory.)
• 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.)
• 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.
• 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.

Sponsors & Collaborators

• Excited States, LLC: lead
• Veristat, Inc.: collaborator
• Biotec Services International Ltd: collaborator
• Eurofins: collaborator
• CBR International Corp.: collaborator

Study Sites (39)

University of South Alabama Medical Center

Mobile, Alabama, 36617, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Sheridan Clinical Research, Inc.

Sunrise, Florida, 33323, United States

Location

University of South Florida/Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Stoger Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Colon & Rectal Surgery Associates

Metairie, Louisiana, 70006, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Ochsner Clinic Foundation / Colon and Rectal Surgery

New Orleans, Louisiana, 70121, United States

Location

Berkshire Medical Center, Inc

Pittsfield, Massachusetts, 01201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Medical IQ

Brandon, Mississippi, 39042, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Colon and Rectal Surgery, Inc.

Omaha, Nebraska, 68114, United States

Location

CentraState Medical Center

Freehold, New Jersey, 07728, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Meridian Health Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Baylor Research Institute

Dallas, Texas, 75207, United States

Location

Methodist Hospital

Houston, Texas, 77030, United States

Location

Southwest Surgical Associates, L.L.P.

Houston, Texas, 77074, United States

Location

Methodist Hospital

San Antonio, Texas, 78229, United States

Location

Southwest Surgical Associates, LLP

Sugar Land, Texas, 77479, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Rambam Medical Center

Haifa, Israel

Location

Hadasit Medical Research Services & Development LTD

Jerusalem, Israel

Location

Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel

Location

The Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, Israel

Location

Related Publications (14)

• Denys, G.A., O'Hanley P, Stephens, JT. E-101 Solution demonstrates antiviral properties against Herpes Simplex Virus, Human Immunodeficiency Virus, and Human Influenza A/H1N1 Virus. American Society for Microbiology, 110th General meeting, San Diego, CA (Abstract # C-2061). May 2010.

  RESULT

• O'Hanley, P, Beausoleil C, O'Hanley K, Stephens, JT. E-101 Solution, a novel antiseptic intended for direct application within a surgical wound to prevent surgical site infection: Blinded, controlled Phase 1 skin irritation study in healthy volunteers. Annual Surgical Site Infection Meeting, Las Vegas, NV, May 2010.

  RESULT

• O'Hanley P, O'Hanley K, Beausoleil C, Stephens JT. E-101 Solution (E-101), a Myeloperoxidase (MPO) Antiseptic for Prevention of Surgical Site Infections (SSI): Phase 1 Sensitization and Microbial Reduction in Healthy Adult Volunteers. Program and Abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, MA, October 2010.

  RESULT

• Pillar, C, Denys GA, O'Hanley P, Stephens JT, Sahm D. E-101, a novel in class topical anti-infective, has potent activity against clinical isolates of important pathogens in Europe collected from 2008-2010. 21st ECCMID/27th ICC, Milan, Italy, May 2011.

  RESULT

• Pillar C, Denys GA, O'Hanley P, Stephens JT, Sahm D. E-101, a novel in class topical anti-infective, maintains a high degree of potency in vitro against problematic resistant clinical pathogens (ESKAPE pathogens). 21st ECCMID/27th ICC, Milan, Italy, May 2011.

  RESULT

• Denys, GA, Goheen MP, Allen RC, O'Hanley P, Stephens JT. Effect of E-101 Solution and its oxidative products on microbial ultrastucture changes associated with microbicidal action. 21st ECCMID/27th ICC, Milan, Italy, May 2011.

  RESULT

• O'Hanley, P, Pete M, O'Hanley K, Sabo L, Allen R, Stephens JT. Antibody Responses Not Likely to Affect Efficacy and Safety of E-101 Solution, a Novel Myeloperoxidase (MPO)-based Topical Antiseptic for Prevention of Incisional Infections. Annual Surgical Site Infection Society Meeting, Palm Beach, FL, May 2011.

  RESULT

• Denys GA, Allen RC, O'Hanley P, Stephens JT. E-101 solution, a first in class topical anti- infective, shows fungicidal activity in vitro against Candida species. 11th ASM Conference on Candida and Candidiasis March 29-April 2, 2012 San Francisco, CA.

  RESULT

• Deane J, Simenauer A, Denys GA, O'Hanley P, Stephens JT, Sahm DF. In vitro activity of E-101, a rapidly bactericidal myeloperoxidase (MPO)-based agent, against key bacterial pathogens. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 9-12, 2012 San Francisco, CA.

  RESULT

• Denys GA, Shah D, Deane D, Sahm DF, O'Hanley P, Stephens JT. Antimicrobial susceptibility of E-101 Solution against target aerobic pathogens: A 5-year longititudional study. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 9-13, 2013 Denver, CO.

  RESULT

• Denys, GA, MP Goheen, RC Allen, P O'Hanley, JT Stephens Jr. Antifungal activity of two potent topical haloperoxidase-based formulations (EPO-based C-101 and MPO-based E- 101) against Candida albicans. American Society for Microbiology, 114th General Meeting, Boston MA (Abstract #681). May 17-20, 2014.

  RESULT

• Denys, GA, C Schneider, P O'Hanley, JT Stephens, Jr., K Babcock. Use of Affinity Biosensor's LifeScale resonant mass measurement to assess antimicrobial activity of E-101 solution, a novel haloperoxidase-based topical antimicrobial agent. American Society for Microbiology, Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington, DC (Abstract F-1573). September 5-9, 2014.

  RESULT

• Denys, GA, KM Koch, RC Allen, P O'Hanley, JT Stephens, Jr. Superiority of E- 101 solution, a haloperoxidase-containing enzyme product, to sodium oxychlorosene as an antiseptic agent in the presence of serum and whole blood. American Society for Microbiology, 115th General Meeting, New Orleans, LA. May 30-June 2, 2015.

  RESULT

• Denys GA, Shah D, Sahm DF, Allen RC, O'Hanley P. Stephens JT. In vitro activity of C- 101 solution, a new eosinophil peroxidase (EPO) containing enzyme system, against Gram- negative and Gram-positive pathogens. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 9-12, 2012 San Francisco, CA.

  RESULT

MeSH Terms

Conditions

Infections; Surgical Wound Infection

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Wound Infection; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Jackson T Stephens, Jr
• Organization: Excited States/Exoxemis, Inc

sstephens@exoxemis.com

(402) 884-2316

Study Officials

• Peter O'Hanley, PhD, MD, MPH

  Excited States, LLC

  STUDY DIRECTOR

• Robert Martindale, MD, PhD

  Oregon Health and Science University

  STUDY CHAIR

• Michael J Stamos, MD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

• Jerrold H Levy, MD

  Emory Healthcare

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2011
• First Posted: February 17, 2011
• Study Start: January 10, 2013
• Primary Completion: October 14, 2015
• Study Completion: October 14, 2015
• Last Updated: February 10, 2021
• Results First Posted: January 19, 2021

Record last verified: 2021-01

Locations

IL (5); US (34)