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

• Sponsor: Excited States, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01297959
• Collaborator: Veristat, Inc. (Other), Biotec Services International Ltd (Other), Eurofins (Industry), CBR International Corp. (Other)
• Enrollment: 503
• Locations: 39
• Arms: 2
• Actual Duration (Months): 33.1
• Patients Per Site: 12.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infections	Drug: E-101 Solution 300 GU/ml; Drug: Saline solution	Phase 3

Detailed Description

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.)

Study Design

• Study Type: Interventional
• Actual Enrollment: 503 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase 3 Study of Efficacy and Safety of Topical E-101 Solution to Prevent Incisional Infections Among Colorectal Surgery Patients (Triple IN Study --Inhibition of Incisional Infections)
• Actual Study Start Date: Jan 10, 2013
• Actual Primary Completion Date: Oct 14, 2015
• Actual Study Completion Date: Oct 14, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: E-101 Solution 300 GU/ml; 8 mL of E-101 Solution
Placebo Comparator: 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.	Drug: Saline solution; Saline solution matched to E-101

Outcome Measures

Primary Outcome Measures

1. 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 [Surgery (Day 0) up to 30 days post-surgery]

   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.

2. 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 [Surgery (Day 0) up to 30 days post-surgery]

   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.

Secondary Outcome Measures

1. Mean Clinical Infection Wound Scale Score (CIWS) [Surgery (Day 0) up to 30 days post-surgery]

   CIWS was used postoperatively to evaluate the primary incisional wound for clinical evidence of infection. Score ranged from 0 (normal) - 5 (worst). 0: normal post-operative wound appearance, 1: wound erythema with pain extending ≥ 2 cm away from the primary incision, 2: spontaneous wound dehiscence with erythema and/or pain extending < 2 cm along primary incision, 3: spontaneous wound dehiscence with erythema and/or pain extending ≥ 2 cm along primary incision, 4: PD from the primary incision, 5: infection of primary incision involving deep incisional structures (muscle and/or fascia) manifested by one or more of the following: spontaneous partial or complete wound dehiscence with erythema and/or pain, spontaneous PD, a wound abscess (based on palpitation findings of the surgeon and/or needle aspiration of purulence into palpable fluctuance, and/or ultrasound examination above the fascia), clinical or histological evidence of fasciitis or myonecrosis.

2. Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI) [Surgery (Day 0) up to 30 days post-surgery]

   Number of participants with objectively determined SSI (defined as participants with PD, wound abscess, or positive microbial culture from one or more incisional samples) are reported.

3. 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]

   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 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 a 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.

4. Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The mobility score questionnaire asked the participants to rate if they had problems walking around on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline mobility scale score was presented.

5. Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The self-care questionnaire asked the participants to rate if they had any problems with self-care on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline self-care scale score was presented.

6. Worst Post-Baseline Usual Activity Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The usual activity questionnaire asked the participants to rate if they had any problems with usual activities on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline usual activity scale score was presented.

7. Worst Post-Baseline Pain/Discomfort Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The pain/discomfort score questionnaire asked the participants to rate if they had any pain or discomfort on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline pain/discomfort scale score was presented.

8. Worst Post-Baseline Anxiety/Depression Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The anxiety/depression questionnaire asked the participants to rate if they had any anxiety or depression on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline anxiety/depression scale score was presented.

9. Worst Post-Baseline Health State Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire [Day 0 up to Day 30]

   The EQ-5D health state scale is a visual analog scale that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating a better state of health. Participants were asked to rate their health state from 0 to 100. The mean worst post-baseline health state score was reported.

10. Number of Participants With Re-Hospitalization [Surgery (Day 0) up to 30 days post-surgery]

    Number of participants who had re-hospitalization for SSI were reported.

11. Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors [Day 3 up to Day 30]

    CWHS was assessed by blind assessors as 0= normal, intact incision without any spontaneous wound dehiscence; 1= spontaneous wound dehiscence that extends < 2 cm along the principal incision in the absence of erythema and/or pain 2= spontaneous wound dehiscence that extends ≥ 2 cm along the principal incision in the absence of erythema and/or pain. Number of participants with various levels of CWHS scores were reported.

12. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs) [From first dose up to 30 days post-surgery]

    AE: Any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. ADR: All noxious and unintended responses to a medicinal product related to any dose. SAE: AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: an event that was not present prior to administration of study medication, or, if present prior to administration of study medication, increases in intensity after administration of study medication during study. SUSAR: all suspected adverse reactions (ARs) related to an investigational medicinal product (IMP) that occurred in study, and that were both unexpected and serious. UAR: an ARs, nature and severity of which was not consistent with the current medicinal product information.

13. Number of Participants With Clinically Significant Laboratory Findings [From first dose up to 30 days post-surgery]

    Number of participants with clinically significant laboratory findings were reported. The clinical significance was decided by the investigator.

14. Number of Participants With Clinically Significant Physical Examination Findings [From first dose up to 30 days post-surgery]

    Number of participants with clinically significant physical examination findings were reported. The clinical significance was decided by the investigator.

15. Number of Participants by Wound Pain Assessment Scores [Surgery (Day 0) up to 30 days post-surgery]

    Number of participants with wound pain assessment scores were assessed on a categorical scale ranging from 0 to 10, where 0 is no pain and 10 is unimaginable, unspeakable pain. Higher number on the scale represents worst possible pain.

16. Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody [Day 14 and Day 30]

    Antibody assessment was done using enzyme-linked immunosorbent assay (ELISA) test.

17. Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody [Month 3 and Month 6]

    Antibody assessment was done using ELISA test.

18. Number of Participants With Serum pANCA and pMPO Antibody Response [Day 30, Month 3 and Month 6]

Other Outcome Measures

1. Minimum Inhibitory Concentration (MIC) at 90% [Surgery (Day 0) up to to 30 days post surgery]

   In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MIC. MIC 90 is defined as the lowest concentration of study drug that inhibits the growth of 90% of aerobic microorganisms tested.

2. Minimum Bactericidal Concentration (MBC) at 90% [Surgery (Day 0) up to to 30 days post surgery]

   In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MBC. MBC 90 is defined as the lowest concentration of study drug required to kill greater than or equal to 99.9% (bactericidal) of the aerobic microorganisms tested.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Medical Center	Mobile	Alabama	United States	36617
2	University of Southern California	Los Angeles	California	United States	90033
3	Stanford University Medical Center	Stanford	California	United States	94305
4	Sheridan Clinical Research, Inc.	Sunrise	Florida	United States	33323
5	University of South Florida/Tampa General Hospital	Tampa	Florida	United States	33606
6	Cleveland Clinic Florida	Weston	Florida	United States	33331
7	Stoger Hospital of Cook County	Chicago	Illinois	United States	60612
8	Indiana University	Indianapolis	Indiana	United States	46202
9	University of Louisville	Louisville	Kentucky	United States	40202
10	Colon & Rectal Surgery Associates	Metairie	Louisiana	United States	70006
11	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
12	Ochsner Clinic Foundation / Colon and Rectal Surgery	New Orleans	Louisiana	United States	70121
13	Berkshire Medical Center, Inc	Pittsfield	Massachusetts	United States	01201
14	Henry Ford Hospital	Detroit	Michigan	United States	48202
15	Medical IQ	Brandon	Mississippi	United States	39042
16	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
17	Colon and Rectal Surgery, Inc.	Omaha	Nebraska	United States	68114
18	CentraState Medical Center	Freehold	New Jersey	United States	07728
19	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
20	Meridian Health Jersey Shore University Medical Center	Neptune	New Jersey	United States	07753
21	Albany Medical Center	Albany	New York	United States	12208
22	Montefiore Medical Center	Bronx	New York	United States	10467
23	Mount Sinai School of Medicine	New York	New York	United States	10029
24	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
25	SUNY Upstate Medical University	Syracuse	New York	United States	13210
26	The Christ Hospital	Cincinnati	Ohio	United States	45219
27	Oregon Health Sciences University	Portland	Oregon	United States	97239
28	Baylor Research Institute	Dallas	Texas	United States	75207
29	Methodist Hospital	Houston	Texas	United States	77030
30	Southwest Surgical Associates, L.L.P.	Houston	Texas	United States	77074
31	Methodist Hospital	San Antonio	Texas	United States	78229
32	Southwest Surgical Associates, LLP	Sugar Land	Texas	United States	77479
33	University of Virginia Health System	Charlottesville	Virginia	United States	22908
34	University of Washington Medical Center	Seattle	Washington	United States	98195
35	Rambam Medical Center	Haifa		Israel
36	Hadasit Medical Research Services & Development LTD	Jerusalem		Israel
37	Rabin Medical Center, Beilinson Hospital	Petah Tikva		Israel
38	The Tel Aviv Sourasky Medical Center	Tel Aviv		Israel
39	The Chaim Sheba Medical Center	Tel Hashomer		Israel

Sponsors and Collaborators

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

Investigators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Excited States, LLC
• ClinicalTrials.gov Identifier: NCT01297959
• Other Study ID Numbers: E-101:PH3:2012:004
• First Posted: Feb 17, 2011
• Last Update Posted: Feb 10, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Excited States, LLC: 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
• Additional relevant MeSH terms: Infections; Communicable Diseases; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 milliliter (mL) of 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 occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Period Title: Overall Study
STARTED	261	242
COMPLETED	241	226
NOT COMPLETED	20	16

Baseline Characteristics

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)	Total
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Total of all reporting groups
Overall Participants	248	234	482
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (14.68)	59.7 (14.36)	59.7 (14.51)
Sex: Female, Male (Count of Participants)
Female	107 43.1%	93 39.7%	200 41.5%
Male	141 56.9%	141 60.3%	282 58.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Asian	5 2%	4 1.7%	9 1.9%
Black	28 11.3%	19 8.1%	47 9.8%
White	211 85.1%	208 88.9%	419 86.9%
Others	3 1.2%	3 1.3%	6 1.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	8 3.2%	7 3%	15 3.1%
Not Hispanic or Latino	235 94.8%	225 96.2%	460 95.4%
Not Reported	3 1.2%	1 0.4%	4 0.8%
Unknown	2 0.8%	1 0.4%	3 0.6%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

ITT Analysis Set included all randomized participants in their assigned treatment group except those were found between randomization and before surgery to either meet exclusion criteria or not meet inclusion criteria, who withdrew consent or were treated at site 03-03 (participants were excluded because of a systematic problem in incisional SSI surveillance due to a lack of blinded assessors). Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	241	225
Count of Participants [Participants]	53 21.4%	41 17.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	E-101 Solution 300 GU/mL, Placebo (Saline Solution)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Regression, Logistic
	Comments	p-value was based on a logistic regression (Chi-square test) model with treatment group as a factor, adjusting for the stratification factors.

2. Primary Outcome

Title	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
Description	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.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

PP Analysis Set included all participants from ITT Analysis Set without any major protocol violations. Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	197	196
Count of Participants [Participants]	41 16.5%	34 14.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	E-101 Solution 300 GU/mL, Placebo (Saline Solution)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Regression, Logistic
	Comments	p-value was based on a logistic regression (Chi-square test) model with treatment group as a factor, adjusting for the stratification factors.

3. Secondary Outcome

Title	Mean Clinical Infection Wound Scale Score (CIWS)
Description	CIWS was used postoperatively to evaluate the primary incisional wound for clinical evidence of infection. Score ranged from 0 (normal) - 5 (worst). 0: normal post-operative wound appearance, 1: wound erythema with pain extending ≥ 2 cm away from the primary incision, 2: spontaneous wound dehiscence with erythema and/or pain extending < 2 cm along primary incision, 3: spontaneous wound dehiscence with erythema and/or pain extending ≥ 2 cm along primary incision, 4: PD from the primary incision, 5: infection of primary incision involving deep incisional structures (muscle and/or fascia) manifested by one or more of the following: spontaneous partial or complete wound dehiscence with erythema and/or pain, spontaneous PD, a wound abscess (based on palpitation findings of the surgeon and/or needle aspiration of purulence into palpable fluctuance, and/or ultrasound examination above the fascia), clinical or histological evidence of fasciitis or myonecrosis.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	235	220
Mean (Standard Deviation) [score on a scale]	0.4 (1.09)	0.4 (1.17)

4. Secondary Outcome

Title	Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)
Description	Number of participants with objectively determined SSI (defined as participants with PD, wound abscess, or positive microbial culture from one or more incisional samples) are reported.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	241	225
Count of Participants [Participants]	33 13.3%	26 11.1%

5. Secondary Outcome

Title	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
Description	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 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 a 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.
Time Frame	Surgery (Day 0) up to 14 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed. Cumulative Treatment Incisional SSI was reported which included Superficial SSI and Deep SSI.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	241	225
Count of Participants [Participants]	50 20.2%	52 22.2%

6. Secondary Outcome

Title	Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The mobility score questionnaire asked the participants to rate if they had problems walking around on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline mobility scale score was presented.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	1.5 (0.56)	1.6 (0.62)

7. Secondary Outcome

Title	Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The self-care questionnaire asked the participants to rate if they had any problems with self-care on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline self-care scale score was presented.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	1.6 (0.68)	1.6 (0.65)

8. Secondary Outcome

Title	Worst Post-Baseline Usual Activity Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The usual activity questionnaire asked the participants to rate if they had any problems with usual activities on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline usual activity scale score was presented.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	2.1 (0.64)	2.0 (0.67)

9. Secondary Outcome

Title	Worst Post-Baseline Pain/Discomfort Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The pain/discomfort score questionnaire asked the participants to rate if they had any pain or discomfort on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline pain/discomfort scale score was presented.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	1.9 (0.53)	1.9 (0.54)

10. Secondary Outcome

Title	Worst Post-Baseline Anxiety/Depression Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The anxiety/depression questionnaire asked the participants to rate if they had any anxiety or depression on a scale of 1 to 3 where 1= no problems, 2= some problems and 3= extreme problems. The mean worst post-baseline anxiety/depression scale score was presented.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	1.4 (0.55)	1.4 (0.60)

11. Secondary Outcome

Title	Worst Post-Baseline Health State Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description	The EQ-5D health state scale is a visual analog scale that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating a better state of health. Participants were asked to rate their health state from 0 to 100. The mean worst post-baseline health state score was reported.
Time Frame	Day 0 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	190	178
Mean (Standard Deviation) [score on a scale]	64.7 (20.77)	61.3 (24.31)

12. Secondary Outcome

Title	Number of Participants With Re-Hospitalization
Description	Number of participants who had re-hospitalization for SSI were reported.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the ITT Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	241	225
Count of Participants [Participants]	6 2.4%	3 1.3%

13. Secondary Outcome

Title	Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors
Description	CWHS was assessed by blind assessors as 0= normal, intact incision without any spontaneous wound dehiscence; 1= spontaneous wound dehiscence that extends < 2 cm along the principal incision in the absence of erythema and/or pain 2= spontaneous wound dehiscence that extends ≥ 2 cm along the principal incision in the absence of erythema and/or pain. Number of participants with various levels of CWHS scores were reported.
Time Frame	Day 3 up to Day 30

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set (all participants randomized to treatment and exposed to any quantity of study drug) with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	206	198
CWHS =0	193 77.8%	185 79.1%
CWHS =1	10 4%	12 5.1%
CWHS =2	3 1.2%	1 0.4%

14. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unexpected Adverse Reactions (UARs)
Description	AE: Any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. ADR: All noxious and unintended responses to a medicinal product related to any dose. SAE: AE that resulted in any of the following: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: an event that was not present prior to administration of study medication, or, if present prior to administration of study medication, increases in intensity after administration of study medication during study. SUSAR: all suspected adverse reactions (ARs) related to an investigational medicinal product (IMP) that occurred in study, and that were both unexpected and serious. UAR: an ARs, nature and severity of which was not consistent with the current medicinal product information.
Time Frame	From first dose up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	248	234
AEs	218 87.9%	202 86.3%
SAEs	57 23%	56 23.9%
TEAEs	215 86.7%	201 85.9%
ADRs	10 4%	10 4.3%
SUSARs	0 0%	0 0%
UARs	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Findings
Description	Number of participants with clinically significant laboratory findings were reported. The clinical significance was decided by the investigator.
Time Frame	From first dose up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	248	234
Count of Participants [Participants]	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With Clinically Significant Physical Examination Findings
Description	Number of participants with clinically significant physical examination findings were reported. The clinical significance was decided by the investigator.
Time Frame	From first dose up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	248	234
Count of Participants [Participants]	0 0%	0 0%

17. Secondary Outcome

Title	Number of Participants by Wound Pain Assessment Scores
Description	Number of participants with wound pain assessment scores were assessed on a categorical scale ranging from 0 to 10, where 0 is no pain and 10 is unimaginable, unspeakable pain. Higher number on the scale represents worst possible pain.
Time Frame	Surgery (Day 0) up to 30 days post-surgery

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available date were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	207	200
Wound Pain Scale Score 0	8 3.2%	9 3.8%
Wound Pain Scale Score 1	7 2.8%	10 4.3%
Wound Pain Scale Score 2	15 6%	20 8.5%
Wound Pain Scale Score 3	25 10.1%	25 10.7%
Wound Pain Scale Score 4	37 14.9%	26 11.1%
Wound Pain Scale Score 5	26 10.5%	31 13.2%
Wound Pain Scale Score 6	29 11.7%	26 11.1%
Wound Pain Scale Score 7	24 9.7%	23 9.8%
Wound Pain Scale Score 8	23 9.3%	18 7.7%
Wound Pain Scale Score 9	3 1.2%	8 3.4%
Wound Pain Scale Score 10	10 4%	4 1.7%

18. Secondary Outcome

Title	Number of Participants With pANCA Immunoglobulin G (IgG) Antibody, Serum Anti-glucose Oxidase (GO) IgG,M,A, pMPO IgG,M,A, Serum GO Neutralization, Serum pMPO Neutralization Antibody
Description	Antibody assessment was done using enzyme-linked immunosorbent assay (ELISA) test.
Time Frame	Day 14 and Day 30

Outcome Measure Data

Analysis Population Description

Participants in the Antibody Safety Set (all participants who were randomized to and exposed to any quantity of study drug with sufficient data to determine antibody results) with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	229	201
pANCA IgG: Day 14	1 0.4%	1 0.4%
pANCA IgG: Day 30	1 0.4%	1 0.4%
Serum Anti-GO IgG,M,A: Day 14	14 5.6%	1 0.4%
Serum Anti-GO IgG,M,A: Day 30	25 10.1%	8 3.4%
Anti-pMPO IgG,M,A: Day 14	48 19.4%	1 0.4%
Anti-pMPO IgG,M,A: Day 30	175 70.6%	1 0.4%
Serum GO Neutralization: Day 14	3 1.2%	0 0%
Serum GO Neutralization: Day 30	6 2.4%	0 0%
Serum pMPO Neutralization: Day 14	1 0.4%	0 0%
Serum pMPO Neutralization: Day 30	18 7.3%	0 0%

19. Secondary Outcome

Title	Number of Participants With pANCA IgG Anti-body, Serum Anti-GO IgG,M,A, pMPO IgG,M,A, Serum Neutralization GO, Serum pMPO Neutralization Antibody
Description	Antibody assessment was done using ELISA test.
Time Frame	Month 3 and Month 6

Outcome Measure Data

Analysis Population Description

Participants in the Antibody Safety Set with available data were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	71	2
pANCA IgG: Month 3	0 0%	0 0%
pANCA IgG: Month 6	0 0%
Serum Anti-GO IgG,M,A: Month 3	3 1.2%	1 0.4%
Serum Anti-GO IgG,M,A: Month 6	1 0.4%
Anti-pMPO IgG,M,A: Month 3	60 24.2%	0 0%
Anti-pMPO IgG,M,A: Month 6	31 12.5%
Serum GO Neutralization: Month 3	0 0%	0 0%
Serum GO Neutralization: Month 6	0 0%
Serum pMPO Neutralization: Month 3	14 5.6%
Serum pMPO Neutralization: Month 6	5 2%

20. Secondary Outcome

Title	Number of Participants With Serum pANCA and pMPO Antibody Response
Time Frame	Day 30, Month 3 and Month 6

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	E-101 Solution 300 GU/mL	Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.	Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	248	234
pANCA: Day 30	1 0.4%	1 0.4%
pANCA: Month 3	0 0%	0 0%
pANCA: Month 6	0 0%	0 0%
Serum pMPO: Day 30	18 7.3%	0 0%
Serum pMPO: Month 3	14 5.6%	0 0%
Serum pMPO: Month 6	5 2%	0 0%

21. Other Pre-specified Outcome

Title	Minimum Inhibitory Concentration (MIC) at 90%
Description	In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MIC. MIC 90 is defined as the lowest concentration of study drug that inhibits the growth of 90% of aerobic microorganisms tested.
Time Frame	Surgery (Day 0) up to to 30 days post surgery

Outcome Measure Data

Analysis Population Description

Per Protocol Analysis Set; only participant samples with isolated pathogens were included in the analysis

Arm/Group Title	E-101 Solution 300 GU/mL
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	50
Measure isolates	76
Aerobic	0.25
Anaerobic	NA

22. Other Pre-specified Outcome

Title	Minimum Bactericidal Concentration (MBC) at 90%
Description	In vitro activity of the study drug against a range of aerobic and anaerobic pathogenic isolates cultured from infected principal incisions was analyzed using MBC. MBC 90 is defined as the lowest concentration of study drug required to kill greater than or equal to 99.9% (bactericidal) of the aerobic microorganisms tested.
Time Frame	Surgery (Day 0) up to to 30 days post surgery

Outcome Measure Data

Analysis Population Description

Per Protocol Analysis Set; only participant samples with isolated pathogens were included in the analysis

Arm/Group Title	E-101 Solution 300 GU/mL
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
Measure Participants	50
Measure isolates	76
Aerobic	0.5
Anaerobic	NA

Adverse Events

Time Frame	From first dose up to 30 days post-surgery
Adverse Event Reporting Description	Safety Analysis Set included all participants randomized to treatment and exposed to any quantity of study drug.
Arm/Group Title	E-101 Solution 300 GU/mL		Placebo (Saline Solution)
Arm/Group Description	Participants received 8 mL of E-101 Solution at pMPO concentration of 300 GU/mL applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.		Participants received placebo (saline solution) matched to E-101 Solution applied topically twice to surgical wound site. The first topical application occurred just after incision to the level of the rectus fascia or linea alba without penetration through the peritoneum and the second topical application occurred just after closure of the rectus fascia or linea alba but prior to closure of the incisional wound.
All Cause Mortality
	E-101 Solution 300 GU/mL		Placebo (Saline Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/248 (0.8%)		2/234 (0.9%)
Serious Adverse Events
	E-101 Solution 300 GU/mL		Placebo (Saline Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/248 (23%)		56/234 (23.9%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/248 (0.4%)		0/234 (0%)
Leukocytosis	1/248 (0.4%)		0/234 (0%)
Cardiac disorders
Angina pectoris	0/248 (0%)		1/234 (0.4%)
Cardiac failure congestive	1/248 (0.4%)		0/234 (0%)
Sinus bradycardia	0/248 (0%)		1/234 (0.4%)
Endocrine disorders
Diabetes insipidus	1/248 (0.4%)		0/234 (0%)
Gastrointestinal disorders
Abdominal distension	1/248 (0.4%)		0/234 (0%)
Abdominal pain	0/248 (0%)		1/234 (0.4%)
Anal fistula	0/248 (0%)		1/234 (0.4%)
Diarrhoea	0/248 (0%)		1/234 (0.4%)
Duodenal ulcer	1/248 (0.4%)		0/234 (0%)
Enteritis	1/248 (0.4%)		0/234 (0%)
Gastrointestinal haemorrhage	1/248 (0.4%)		0/234 (0%)
Ileus	3/248 (1.2%)		2/234 (0.9%)
Intestinal ischaemia	1/248 (0.4%)		0/234 (0%)
Intestinal obstruction	1/248 (0.4%)		0/234 (0%)
Intestinal perforation	1/248 (0.4%)		0/234 (0%)
Intra-abdominal haemorrhage	1/248 (0.4%)		0/234 (0%)
Large intestine perforation	1/248 (0.4%)		0/234 (0%)
Melaena	0/248 (0%)		1/234 (0.4%)
Nausea	0/248 (0%)		2/234 (0.9%)
Pancreatitis	2/248 (0.8%)		0/234 (0%)
Rectal haemorrhage	1/248 (0.4%)		0/234 (0%)
Small intestinal obstruction	2/248 (0.8%)		4/234 (1.7%)
Vomiting	1/248 (0.4%)		2/234 (0.9%)
General disorders
Fat necrosis	1/248 (0.4%)		0/234 (0%)
Fatigue	0/248 (0%)		1/234 (0.4%)
Pyrexia	1/248 (0.4%)		0/234 (0%)
Secretion discharge	1/248 (0.4%)		0/234 (0%)
Hepatobiliary disorders
Portal vein thrombosis	1/248 (0.4%)		0/234 (0%)
Infections and infestations
Abdominal abscess	2/248 (0.8%)		3/234 (1.3%)
Abdominal infection	0/248 (0%)		1/234 (0.4%)
Abdominal wall abscess	1/248 (0.4%)		0/234 (0%)
Abscess	0/248 (0%)		1/234 (0.4%)
Bacteraemia	0/248 (0%)		1/234 (0.4%)
Cellulitis	1/248 (0.4%)		1/234 (0.4%)
Clostridium difficile infection	1/248 (0.4%)		0/234 (0%)
Empyema	0/248 (0%)		1/234 (0.4%)
Gastroenteritis viral	1/248 (0.4%)		0/234 (0%)
Graft infection	1/248 (0.4%)		0/234 (0%)
Pelvic infection	1/248 (0.4%)		1/234 (0.4%)
Pericolic abscess	1/248 (0.4%)		0/234 (0%)
Peritonitis	1/248 (0.4%)		1/234 (0.4%)
Pneumonia	1/248 (0.4%)		5/234 (2.1%)
Post procedural sepsis	0/248 (0%)		1/234 (0.4%)
Pyelonephritis	0/248 (0%)		1/234 (0.4%)
Sepsis	4/248 (1.6%)		2/234 (0.9%)
Subdiaphragmatic abscess	0/248 (0%)		1/234 (0.4%)
Thrombophlebitis septic	1/248 (0.4%)		0/234 (0%)
Urinary tract infection	2/248 (0.8%)		0/234 (0%)
Urinary tract infection bacterial	0/248 (0%)		1/234 (0.4%)
Injury, poisoning and procedural complications
Anastomotic leak	7/248 (2.8%)		9/234 (3.8%)
Gastrointestinal stoma complication	1/248 (0.4%)		2/234 (0.9%)
Post procedural haemorrhage	0/248 (0%)		1/234 (0.4%)
Postoperative fever	1/248 (0.4%)		0/234 (0%)
Postoperative ileus	2/248 (0.8%)		4/234 (1.7%)
Seroma	0/248 (0%)		1/234 (0.4%)
Ureteric injury	1/248 (0.4%)		0/234 (0%)
Investigations
Blood creatinine increased	1/248 (0.4%)		0/234 (0%)
Metabolism and nutrition disorders
Dehydration	5/248 (2%)		3/234 (1.3%)
Musculoskeletal and connective tissue disorders
Fistula	1/248 (0.4%)		0/234 (0%)
Osteoarthritis	0/248 (0%)		1/234 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma	0/248 (0%)		1/234 (0.4%)
Renal and urinary disorders
Renal failure	1/248 (0.4%)		0/234 (0%)
Renal failure acute	0/248 (0%)		1/234 (0.4%)
Urinary retention	0/248 (0%)		2/234 (0.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/248 (0.4%)		0/234 (0%)
Chronic obstructive pulmonary disease	0/248 (0%)		1/234 (0.4%)
Dyspnoea	0/248 (0%)		1/234 (0.4%)
Haemothorax	1/248 (0.4%)		0/234 (0%)
Pneumonia aspiration	0/248 (0%)		1/234 (0.4%)
Pulmonary embolism	1/248 (0.4%)		0/234 (0%)
Pulmonary oedema	1/248 (0.4%)		0/234 (0%)
Respiratory distress	1/248 (0.4%)		0/234 (0%)
Respiratory failure	0/248 (0%)		1/234 (0.4%)
Surgical and medical procedures
Abscess drainage	0/248 (0%)		1/234 (0.4%)
Vascular disorders
Orthostatic hypotension	0/248 (0%)		1/234 (0.4%)
Other (Not Including Serious) Adverse Events
	E-101 Solution 300 GU/mL		Placebo (Saline Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	180/248 (72.6%)		174/234 (74.4%)
Cardiac disorders
Tachycardia	27/248 (10.9%)		29/234 (12.4%)
Gastrointestinal disorders
Abdominal distension	20/248 (8.1%)		28/234 (12%)
Constipation	17/248 (6.9%)		14/234 (6%)
Diarrhoea	14/248 (5.6%)		14/234 (6%)
Dyspepsia	15/248 (6%)		11/234 (4.7%)
Nausea	98/248 (39.5%)		93/234 (39.7%)
Vomiting	34/248 (13.7%)		40/234 (17.1%)
General disorders
Pyrexia	38/248 (15.3%)		35/234 (15%)
Injury, poisoning and procedural complications
Gastrointestinal stoma complication	13/248 (5.2%)		8/234 (3.4%)
Investigations
Blood magnesium decreased	11/248 (4.4%)		18/234 (7.7%)
Blood phosphorus decreased	12/248 (4.8%)		19/234 (8.1%)
Haemoglobin decreased	12/248 (4.8%)		19/234 (8.1%)
Oxygen saturation decreased	13/248 (5.2%)		17/234 (7.3%)
Urine output decreased	5/248 (2%)		17/234 (7.3%)
Metabolism and nutrition disorders
Hypokalaemia	31/248 (12.5%)		30/234 (12.8%)
Hypomagnesaemia	22/248 (8.9%)		24/234 (10.3%)
Hypophosphataemia	19/248 (7.7%)		11/234 (4.7%)
Psychiatric disorders
Insomnia	17/248 (6.9%)		20/234 (8.5%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	7/248 (2.8%)		16/234 (6.8%)
Skin and subcutaneous tissue disorders
Pruritus	20/248 (8.1%)		16/234 (6.8%)
Vascular disorders
Hypotension	22/248 (8.9%)		19/234 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.