Colorectal Surgery, Surgical Wound Infection
Conditions
Keywords
Colorectal surgery
Brief summary
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
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.
Interventions
2 gentamicin-collagen sponges inserted before closure of the laparotomy
Sponsors
Duke University
Premier Research
Innocoll
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 60 | assessed at Postop Day 1, 2, 3, 7, 30 & 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Superficial Incisional Surgical Wound Infection | assessed at Postop Day 1, 2, 3, 7, 30 & 60 | Number of Participants who had superficial incisional surgical wound infection, based on CDC criteria adjudicated by an independent blinded committee |
| The Effect of the Gentamicin-collagen Sponge on the Proportion of Patients With Deep Incisional Surgical Wound Infection | assessed at Postop Day 1, 2, 3, 7, 30 & 60 | 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 |
| The Effect of the Gentamicin-collagen Sponge on the ASEPSIS Score | Days 3, 4, 5, 6, and 7 (or discharge if earlier) and then questionnaire/phone call on post-operative Days 30 and 60. | 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 |
| 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 | Through 60 days after surgery | The effect of the gentamicin-collagen sponge on rehospitalization for surgical wound infection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gentamicin Group Group 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).
gentamicin-collagen sponge dipped in saline: 2 gentamicin-collagen sponges inserted before closure of the laparotomy | 300 |
| Control Group Standard of care, ie, no gentamicin-collagen sponge. | 302 |
| Total | 602 |
Baseline characteristics
| Characteristic | Control Group | Total | Gentamicin Group Group |
|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 15.81 | 56.7 Years STANDARD_DEVIATION 15.57 | 56.9 Years STANDARD_DEVIATION 15.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 41 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 273 Participants | 545 Participants | 272 Participants |
| Sex: Female, Male Female | 158 Participants | 339 Participants | 181 Participants |
| Sex: Female, Male Male | 144 Participants | 263 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 296 | 5 / 306 |
| other Total, other adverse events | 294 / 296 | 302 / 306 |
| serious Total, serious adverse events | 114 / 296 | 101 / 306 |
Outcome results
Primary
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.
Time frame: assessed at Postop Day 1, 2, 3, 7, 30 & 60
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gentamicin Group | Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 60 | 90 Participants |
| Control | Number of Participants With Surgical Wound Infections From Surgery Through Post-operative Day 60 | 63 Participants |
Secondary
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
Time frame: assessed at Postop Day 1, 2, 3, 7, 30 & 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gentamicin Group | Number of Participants Who Had Superficial Incisional Surgical Wound Infection | 61 Participants |
| Control | Number of Participants Who Had Superficial Incisional Surgical Wound Infection | 41 Participants |
Secondary
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.
Time frame: Through 60 days after surgery
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gentamicin Group | Number of Participants Who Were Rehospitalized for Surgical Wound Infection Within 60 Days Post-operatively | 21 Participants |
| Control | Number of Participants Who Were Rehospitalized for Surgical Wound Infection Within 60 Days Post-operatively | 13 Participants |
Secondary
The Effect of the Gentamicin-collagen Sponge on Length of Hospital Stay Postoperatively.
Time frame: Immediate post operative period
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gentamicin Group | The Effect of the Gentamicin-collagen Sponge on Length of Hospital Stay Postoperatively. | 7.5 days | Standard Deviation 6.19 |
| Control | The Effect of the Gentamicin-collagen Sponge on Length of Hospital Stay Postoperatively. | 7.3 days | Standard Deviation 5.42 |
Secondary
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
Time frame: Days 3, 4, 5, 6, and 7 (or discharge if earlier) and then questionnaire/phone call on post-operative Days 30 and 60.
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gentamicin Group | The Effect of the Gentamicin-collagen Sponge on the ASEPSIS Score | 6.1 score on a scale | Standard Deviation 10.38 |
| Control | The Effect of the Gentamicin-collagen Sponge on the ASEPSIS Score | 5.2 score on a scale | Standard Deviation 10.99 |
Secondary
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
Time frame: assessed at Postop Day 1, 2, 3, 7, 30 & 60
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gentamicin Group | The Effect of the Gentamicin-collagen Sponge on the Proportion of Patients With Deep Incisional Surgical Wound Infection | 25 Participants |
| Control | The Effect of the Gentamicin-collagen Sponge on the Proportion of Patients With Deep Incisional Surgical Wound Infection | 18 Participants |