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

NCT ID: NCT01297959

Last Updated: 2021-02-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

503 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-10

Study Completion Date

2015-10-14

Brief Summary

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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.

Detailed Description

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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.)

Conditions

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Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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E-101 Solution 300 GU/mL

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.

Group Type EXPERIMENTAL

E-101 Solution 300 GU/ml

Intervention Type DRUG

8 mL of E-101 Solution

Placebo (Saline solution)

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.

Group Type PLACEBO_COMPARATOR

Saline solution

Intervention Type DRUG

Saline solution matched to E-101

Interventions

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E-101 Solution 300 GU/ml

8 mL of E-101 Solution

Intervention Type DRUG

Saline solution

Saline solution matched to E-101

Intervention Type DRUG

Eligibility Criteria

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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. If female, is non-pregnant (negative pregnancy test result at the Screening/Randomization Visit) and non-lactating.
4. 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., perinuclear anti-neutrophil cytoplasmic antibody \[pANCA\]), as well as participants with known idiopathic necrotizing glomerulonephritis and certain systemic vasculitis conditions \[e.g., microscopic polyangiitis of small blood vessels, Wegener's granulomatosis, and Churg-Strauss Syndrome\]).
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 participant 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. American Society of Anesthesiologists (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. Participants 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 international normalized ratio (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 participant 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. Participant with severe Chronic obstructive pulmonary disease (COPD) that are likely to need \> 24 hours postoperative ventilator support (e.g. participant 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 participant would likely be unable to maintain adequate care of the principal incision post-operatively.
26. Anticipate that participant will not be available for study visits/ procedures or if in the opinion of Investigator there is concern that participant 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Veristat, Inc.

OTHER

Sponsor Role collaborator

Biotec Services International Ltd

OTHER

Sponsor Role collaborator

Eurofins

INDUSTRY

Sponsor Role collaborator

CBR International Corp.

INDUSTRY

Sponsor Role collaborator

Excited States, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter O'Hanley, PhD, MD, MPH

Role: STUDY_DIRECTOR

Excited States, LLC

Robert Martindale, MD, PhD

Role: STUDY_CHAIR

Oregon Health and Science University

Michael J Stamos, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Irvine

Jerrold H Levy, MD

Role: PRINCIPAL_INVESTIGATOR

Emory Healthcare

Locations

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University of South Alabama Medical Center

Mobile, Alabama, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Sheridan Clinical Research, Inc.

Sunrise, Florida, United States

Site Status

University of South Florida/Tampa General Hospital

Tampa, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Stoger Hospital of Cook County

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Colon & Rectal Surgery Associates

Metairie, Louisiana, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation / Colon and Rectal Surgery

New Orleans, Louisiana, United States

Site Status

Berkshire Medical Center, Inc

Pittsfield, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Medical IQ

Brandon, Mississippi, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Colon and Rectal Surgery, Inc.

Omaha, Nebraska, United States

Site Status

CentraState Medical Center

Freehold, New Jersey, United States

Site Status

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Meridian Health Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

The Christ Hospital

Cincinnati, Ohio, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Baylor Research Institute

Dallas, Texas, United States

Site Status

Methodist Hospital

Houston, Texas, United States

Site Status

Southwest Surgical Associates, L.L.P.

Houston, Texas, United States

Site Status

Methodist Hospital

San Antonio, Texas, United States

Site Status

Southwest Surgical Associates, LLP

Sugar Land, Texas, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Hadasit Medical Research Services & Development LTD

Jerusalem, , Israel

Site Status

Rabin Medical Center, Beilinson Hospital

Petah Tikva, , Israel

Site Status

The Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

Countries

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United States Israel

References

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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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type 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.

Reference Type RESULT

Other Identifiers

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E-101:PH3:2012:004

Identifier Type: -

Identifier Source: org_study_id

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