A Study of an Antibiotic Implant in General Surgical Subjects at Higher Risk for Surgical Wound Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the gentamicin-collagen sponge is safe and effective for preventing surgical wound infections in patients undergoing colorectal surgery.

Detailed Description
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Surgical wound infection (SWI) is a significant problem in colorectal surgery. Despite the use of routine bowel preparation and prophylactic antibiotics the incidence of SWI is at least 15% in patients undergoing colorectal surgical procedures.Therefore, there is a long unmet need for an intervention that can reduce the incidence and severity of SWIs in patients undergoing colorectal surgery. Gentamicin is an antibiotic that is effective in treating certain kinds of infection. Collagen is a protein that is found in all mammals. The gentamicin-collagen sponge is a thin flat sponge made out of collagen that comes from cow tendons and containing gentamicin. When inserted into a surgical site, the collagen breaks down and the gentamicin is released at the site but very little is absorbed into the blood stream. The high levels of antibiotic at the surgical site may prevent an infection at the surgical site. Outside of the United States more than 3,500 subjects have received treatment in clinical studies with the gentamicin-collagen sponge, primarily for orthopedic, intraabdominal, and cardiothoracic surgeries or wound infections following surgical procedures or traumatic events. In this study, all subjects will be given treatment that is normally given to prevent surgical infections. For subjects randomly assigned to the gentamicin-collagen sponge treatment group, 2 sponges will be inserted into the surgical wound immediately before the surgeon closes it. The control group will receive no collagen sponge.

Official Title
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A Randomized, Controlled, Phase 3 Study of Gentamicin-Collagen Sponge in General Surgical Subjects at Higher Risk for Surgical Wound Infection

Conditions
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Colorectal Surgery, Surgical Wound Infection

Intervention / Treatment
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* Drug: gentamicin-collagen sponge dipped in saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled to undergo nonemergent colon and/or rectal surgical procedures involving a laparotomy incision of at least 7 cm in length or greater. List of eligible procedures: Left Hemicolectomy, Transverse Colectomy, Segmental/Sleeve Left Colon Resection, Total Abdominal Colectomy With Ileorectal Anastomosis, Total Abdominal Colectomy With Ileostomy, Total Abdominal Proctocolectomy (Portion Of Specimen To Be Extracted Via Laparotomy), Low Anterior Resection, Sigmoid Resection, Non-Emergent Hartmann's Procedure, Colotomy With Polypectomy Distal To Hepatic Flexure, Colostomy Takedown Through Laparotomy (Not Peristomal) Incision, Ileo-Pouch Anal Anastomosis, Abdominal Perineal Resection of the Rectum Have the capacity to understand and sign an informed consent form. Are male or female and > 18 years of age. If female, be postmenopausal (no menstrual period for a minimum of 1 year), or surgically sterilized (does not have a uterus or has had bilateral tubal ligation). Females of child-bearing potential must have a negative serum pregnancy test on entry in the study, and agree to use adequate birth control during the study and for 60 days after the administration of study agent. Agree to be available for evaluation from baseline until final evaluation at 60 days postsurgery. Exclusion Criteria: Known history of hypersensitivity to gentamicin or bovine collagen. Undergoing emergency surgery (urgent surgery is allowed if informed consent is obtained and the study procedures can be performed). Emergency surgery includes cases where standard bowel preparation and other preoperative assessments cannot be done. Undergoing a significant concomitant surgical procedure (e.g., hysterectomy). The following concomitant procedures are allowed: appendectomy, cholecystectomy, oophorectomy, liver biopsy/wedge resection (but not liver resection). Undergoing a laparoscopic, laparoscopic-assisted, or other minimally invasive surgical approach involving a laparotomy incision less than 7 cm. History of prior laparotomy within the last 60 days of this planned procedure. Planned to undergo a second laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 60 days of this planned first procedure. Evidence preoperatively of any of the following: sepsis, severe sepsis, or septic shock (note that SIRS alone is not an exclusion criterion) Current abdominal wall infection/surgical site infection from previous laparotomy/laparoscopy or for any reason. Receiving antibiotic therapy within the 1 week prior to the date of surgery. Preoperative evaluation suggests intra-abdominal process that might preclude full closure of the skin. History of ongoing treatment (e.g. chemotherapy, radiation) for non-colorectal cancer. Recent history of significant drug or alcohol abuse. Preoperative prothrombin time (PT) > 1.5 times upper limit of normal Pregnant, lactating, or of childbearing potential not practicing a birth control method with a high degree of reliability Postsurgical life expectancy ≤ 60 days, in the investigator's or sponsor's opinion. Refusal to accept medically indicated blood products. Previous participation in this or any other active Innocoll Gentamicin-Collagen Sponge study. 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. Surgeon does not believe that it will be possible to insert 2 sponges above the fascia in the patient (e.g. in a very thin patient planned to have a small incision) Patients with anterior abdominal wall mesh that is not planned to be completely removed during the planned procedure. Presence of prosthetic cardiac valve.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Insertion of 2 gentamicin-collagen sponges before closure of the laparotomy (each 10 x 10 cm sponge contains 280 mg collagen and 130 mg gentamicin). | Drug: gentamicin-collagen sponge dipped in saline<br>* 2 gentamicin-collagen sponges inserted before closure of the laparotomy<br>|
| No Intervention: 2<br>Standard of care, ie, no gentamicin-collagen sponge. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 60 | Primarily, efficacy will be evaluated by a comparison between the 2 study groups of the incidence of surgical wound infections (involving the laparotomy incision) that occur within the period from surgery through postop day 60. | assessed at Postop Day 1, 2, 3, 7, 30 & 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had Superficial Incisional Surgical Wound Infection | Number of Participants who had superficial incisional surgical wound infection, based on CDC criteria adjudicated by an independent blinded committee | assessed at Postop Day 1, 2, 3, 7, 30 & 60 | 
| The Effect of the Gentamicin-collagen Sponge on the Proportion of Patients With Deep Incisional Surgical Wound Infection | The proportion of subjects who had deep incisional SWI, based on Centers for Disease Control and Prevention (CDC) criteria adjudicated by an independent blinded committee | assessed at Postop Day 1, 2, 3, 7, 30 & 60 | 
| The Effect of the Gentamicin-collagen Sponge on the ASEPSIS Score | Mean (SD) ASEPSIS Score Through 60 Days Postoperatively - brief assessment of surgical wound on post-operative Days 3, 4, 5, 6, and 7 (or discharge if earlier) and then questionnaire/phone call on post-operative Days 30 and 60. Score from each time point is added up and the mean score is reported. Used to compare antibiotic regimens for their effectiveness in preventing or treating wound sepsis, well-defined criteria for outcome are needed. A method of assessing wound healing has been devised that defines carefully the characteristics to be considered and how they are to be awarded points. Objective criteria are also included in the assessment. Points are given for the need for Additional treatment, the presence of Serous discharge, Erythema, Purulent exudate, and Separation of the deep tissues, the Isolation of bacteria, and the duration of inpatient Stay (ASEPSIS). The higher the points the worse outcome. Maximum Points would be 60. Minimum points would be 0 | Days 3, 4, 5, 6, and 7 (or discharge if earlier) and then questionnaire/phone call on post-operative Days 30 and 60. | 
| The Effect of the Gentamicin-collagen Sponge on Length of Hospital Stay Postoperatively. |  | Immediate post operative period | 
| Number of Participants Who Were Rehospitalized for Surgical Wound Infection Within 60 Days Post-operatively | The effect of the gentamicin-collagen sponge on rehospitalization for surgical wound infection. | Through 60 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal surgery