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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 503
- 试验地点
- 38
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled to undergo elective colon and/or rectal surgical procedures involving open laparotomy, hand-assisted laparoscopy, and laparoscopic-assisted approaches. The principal incision must have a length of > 5 cm and < 35 cm in length. Eligible surgeries are: left hemicolectomy, right hemicolectomy, transverse colectomy, ileocolic resection, total abdominal colectomy with ileorectal anastomosis, total abdominal proctocolectomy (portion of specimen to be extracted via laparotomy), low anterior resection, sigmoid resection, non-emergent Hartmann procedure, colostomy takedown through laparotomy (not peristomal) incision, ileo-pouch anal anastomosis, and abdominal perineal resection of the rectum.
- •Able to give informed consent.
- •If female, is non-pregnant (negative pregnancy test result at the Screening/Randomization Visit) and non-lactating.
- •If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [status post bilateral tubal occlusion, bilateral oophorectomy, or hysterectomy]) or practicing 1 of the following methods of birth control and agrees to continue with this regimen over the study surveillance period:
- •Oral, implantable, or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit
- •Intrauterine device
- •Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream)
- •Not sexually-active. Agreement to be available for evaluation at the study site for scheduled visits.
排除标准
- •Hypersensitivity to porcine products.
- •History of known anti-myeloperoxidase autoantibodies (i.e., perinuclear anti-neutrophil cytoplasmic antibody [pANCA]), as well as participants with known idiopathic necrotizing glomerulonephritis and certain systemic vasculitis conditions [e.g., microscopic polyangiitis of small blood vessels, Wegener's granulomatosis, and Churg-Strauss Syndrome]).
- •Use of microbial sealant (IntegusealTM), any antibiotic-embedded suture, or any antimicrobial-embedded suture to close the principal incision or any suture in the surgical field that has not been formally approved by the relevant local national regulatory authority.
- •Absolute contraindication to general anesthesia.
- •Hypersensitivity reactions to steri-strip tapes, medical-surgery tapes, adhesives, or sutures. (Note: If there can be assurances that the participant will not be exposed to these materials that cause hypersensitivity, alternatives will be allowed.)
- •History of keloid or hypertrophic scarring within or near an incision from a prior surgery.
- •Body mass index [BMI]: > 50 or < 20 (both due to the extremely high risk of poor wound healing).
- •American Society of Anesthesiologists (ASA) Score >
- •Undergoing emergency colorectal surgery such that standard bowel preparation and other standard preoperative precautions and assessments cannot be performed in time before the index-surgery.
- •The planned index-surgery involves removal or placement of mesh (either synthetic or biological) as part of closure in the principal incision or traversing any part of a pre-existing mesh (either synthetic or biological) in the principal incision.
- •There are clinical signs of overt infection necessitating systemic antibiotics via oral, intramuscular, or intravenous routes (e.g., infection of the abdominal wall, peritonitis, pneumonia, and sepsis/septic shock) prior to the index-surgery.
- •Preoperative severe neutropenia (total neutrophil count ≤500 X 109/L). (Note: Testing should be performed at the local laboratory.)
- •Receiving any oral or intravenous antibiotics within 24 hours prior to the index-surgery. (Note: It is permissible to administer conventional oral prophylactic antibiotics as bowel preparation up to the time of the index- surgical procedure, as well as intravenous or intramuscular prophylactic antibiotics just prior to the index-surgery as per the treating surgeon's standard of care.)
- •Preoperative evaluation that the intra-abdominal process might preclude full closure of the skin incision due to severe or morbid obesity (i.e., any mechanical reason that would prevent/preclude primary intent wound healing) at the principal incision.
- •History of major organ transplantation (e.g., lung, liver, or kidney), including bone marrow transplantation, or intent to perform major organ transplant as a concomitant surgery.
- •History of a complicated laparotomy within 30 days prior to planned index-surgery.
- •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.
- •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.)
- •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).
- •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).
- •Preoperative prothrombin time or international normalized ratio (INR) > 2 x upper limit of normal. (Note: Testing should be performed at the local laboratory.)
- •Postsurgical life expectancy ≤ 60 days (in the Investigator's or Sponsor's opinion).
- •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.
- •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).
- •If, in the opinion of Investigator, the potential participant would likely be unable to maintain adequate care of the principal incision post-operatively.
- •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).
- •Lack of willingness to have personal study-related data collected, archived, or transmitted under a blinded condition to regulatory agencies.
- •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.
研究组 & 干预措施
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.
干预措施: E-101 Solution 300 GU/ml (Drug)
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.
干预措施: Saline solution (Drug)
结局指标
主要结局
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
时间窗: 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.
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
时间窗: 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.
次要结局
- Number of Participants With Objectively Determined Incisional Surgical Site Infections (SSI)(Surgery (Day 0) up to 30 days post-surgery)
- Mean Clinical Infection Wound Scale Score (CIWS)(Surgery (Day 0) up to 30 days post-surgery)
- Number of Participants With Superficial and Deep Incisional Surgical Site Infections (SSI) Involving the Principal Incision (PI) Within 30 Days After the Index-surgery as Determined by Blinded Assessors 14 Days Post-operatively(Surgery (Day 0) up to 14 days post-surgery)
- Worst Post-Baseline Mobility Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Worst Post-Baseline Self-Care Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Worst Post-Baseline Pain/Discomfort Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Worst Post-Baseline Usual Activity Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Worst Post-Baseline Anxiety/Depression Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Worst Post-Baseline Health State Score Using European Quality of Life-5 Dimensions (EQ-5D) Questionnaire(Day 0 up to Day 30)
- Number of Participants With Re-Hospitalization(Surgery (Day 0) up to 30 days post-surgery)
- Number of Participants With Clinical Wound Healing Score (CWHS) as Assessed by Blinded Assessors(Day 3 up to Day 30)
- 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)
- Number of Participants With Clinically Significant Laboratory Findings(From first dose up to 30 days post-surgery)
- Number of Participants With Clinically Significant Physical Examination Findings(From first dose up to 30 days post-surgery)
- Number of Participants by Wound Pain Assessment Scores(Surgery (Day 0) up to 30 days post-surgery)
- 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)
- 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)
- Number of Participants With Serum pANCA and pMPO Antibody Response(Day 30, Month 3 and Month 6)