Skin Flora Contamination
Conditions
Keywords
cyanoacrylates, microbial sealants, skin flora contamination, surgery
Brief summary
The purpose of this study is to determine if there is a qualitative reduction in microbial skin flora post-surgery compared to pre-surgery when a cyanoacrylate based microbial sealant is used in combination with a surgical skin preparation solution.
Detailed description
The CDC states that there are two sources of surgical site infection (SSI) pathogens- endogenous and exogenous. The endogenous flora of the patient's skin, mucous membranes, or hollow viscera are the source of pathogens for most SSIs. In addition to the known sources of SSI pathogen, there are also known risk factors for SSI. The risk factors for SSIs may be patient-related, or related to the preoperative, intra-operative, and post-operative surgical treatment and care of the patient. Many known risk factors that contribute to SSIs include, but are not limited to age, nutritional status, co-morbidities, length of pre-operative stay, duration of operation, preoperative skin prep, and surgical techniques. In addition, there are certain surgical procedures in which the risks for developing SSI are greater than other surgical procedures. While there are various pre-operative and post-operative techniques or approaches to prevent these infections in patients undergoing surgeries, such as pre-operative skin care techniques, appropriate use of antibiotic prophylaxis, and the use of other post-operative anti-microbial methods, by immobilizing the patient's endogenous skin flora, an opportunity exists to reduce the rate of skin flora contamination which leads to wound contamination.
Interventions
PROCEDUREInteguSeal* skin sealant and standard surgical preparation
Surgical skin preparation prior to incision using InteguSeal\* skin sealant following standard surgical preparation with povidone iodine or 0.7% available iodine in isopropyl alcohol 74% w/w.
OTHERStandard preoperative skin preparation
Surgical skin preparation prior to incision using standard surgical preparation with povidone iodine or 0.7% available iodine in isopropyl alcohol 74% w/w.
Sponsors
Kimberly-Clark Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Scheduled for an elective Coronary Artery Bypass Graft (CABG) surgical procedure with median sternotomy utilizing either the saphenous vein and/or radial artery as one of the graft sites within 28 days of the screening date, as documented by a Cardiothoracic Surgeon who is the Principal Investigator or sub-investigator. This includes subjects who are also receiving internal mammary artery grafts in addition to saphenous vein and/or radial artery grafts. * The skin near or around the proposed incision sites should be intact.
Exclusion criteria
* Known sensitivity or allergy to cyanoacrylate, isopropyl alcohol, iodine or iodine-containing products or tape allergies. * Female subjects that are nursing or actively lactating. * Abnormal skin condition adjacent to or at the surgical incision sites. * Hair removal at the surgical sites prior to entrance to the operating suite. * Use of antimicrobial impregnated incise drapes (i.e. Ioban®). * Hospital stay of \>14 days immediately prior to scheduled CABG surgery. * Use of chemotherapy agents, within 30 days prior to Visit 1 screening. * Scheduled for additional chemotherapy for the duration of the study. * Known positive Human Immunodeficiency Virus (HIV) with a CD4 count \< 350 mm3. If HIV status is not known, the subject is not excluded. * Currently taking antibiotics for an infection (within 30 days prior to Visit 1). * Has had therapeutic radiation to the chest within 30 days of visit 1. This does not include subjects who receive chest xrays. * Pre-operatively scheduled to have concomitant procedures with coronary artery bypass graft procedure. * Scheduled to receive only one incision (a median sternotomy) without a planned saphenous vein graft and/or a radial artery graft donor site. * Renal dialysis currently or within 30 days of visit 1. * Morbid Obesity (Subjects with a Body Mass Index (BMI) \> 37). * Neutropenia (absolute neutrophil count \<1000/mm3). * Pre-operatively on an intra-aortic balloon pump or mechanical assist device. * Has received an experimental drug or used an experimental medical device within 30 days prior to Visit 1. * Employees of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that investigator or study center. * Any condition, which in the opinion of the investigator would exclude the subject from the study. * Patients on steroid use for more than 1 week within 30 days of visit 1. * Patients on immunosuppressive therapy within 30 days of visit 1. * Depilatory creams with containing antibiotics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Sternal Site | Before surgery (prior to skin preparation) and after surgery (after closing fascia) | Number of unique bacterial colony types isolated from samples of skin flora taken from the sternal incision site after surgery minus before surgery (prior to skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests. |
| Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Graft Site | Before surgery (prior to skin preparation) and after surgery (after closing fascia) | Number of unique bacterial colony types isolated from samples of skin flora taken from the graft incision site after surgery minus before surgery (prior to skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-CABG Procedure Bacterial Count - Sternal Site | Post-surgery | Total bacterial counts from samples of skin flora of the sternal incision site taken immediately following the CABG procedure. |
| Post-CABG Procedure Bacterial Count - Graft Site | Post-surgery | Total bacterial counts from samples of skin flora of the graft incision site taken immediately following the CABG procedure. |
| Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Sternal Site | Before surgery (prior to skin preparation) and immediately after incision | Number of unique bacterial colony types isolated from samples of skin flora from the sternal incision site immediately after the incision minus before surgery (prior to surgical skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests. |
| Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Graft Site | Before surgery (prior to skin preparation) and immediately after incision | Number of unique bacterial colony types isolated from samples of skin flora from the graft incision site immediately after the incision minus before surgery (prior to surgical skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests. |
| Change in Bacterial Count From Pre-skin Preparation to Post-incision - Sternal Site | Before surgery (prior to skin preparation) and immediately after incision | Total bacterial counts from samples of skin flora from the sternal incision site immediately after incision minus before surgery (prior to skin prep) |
| Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Sternal Site | Before surgery (prior to skin preparation) and after surgery (after closing fascia) | Total bacterial counts from samples of skin flora from the sternal incision site after surgery minus before surgery (prior to skin prep). |
| Post-incision Bacterial Count - Sternal Site | Immediately after surgical incision | Total bacterial counts from samples of skin flora of the sternal incision site taken immediately following the surgical incision |
| Post-incision Bacterial Count - Graft Site | Immediately after surgical incision | Total bacterial counts from samples of skin flora of the graft incision site taken immediately following the surgical incision |
| Number of Patients With SSI at the Sternal Site and/or Graft Site | 30 days | Number of patients who develop at least one surgical site infection at the sternal or graft site during the 30 day post-op follow-up period |
| Number of Patients With Alcohol Use, Tobacco Use, or Obesity With Surgical Site Infection (SSI) | 30 days | Number of patients with risk factors of alcohol use, tobacco use, or obesity who developed an SSI at the sternal and/or graft site |
| Change in Bacterial Count From Pre-skin Preparation to Post-incision - Graft Site | Before surgery (prior to skin preparation) and immediately after incision | Total bacterial counts from samples of skin flora from the graft incision site immediately after incision minus before surgery (prior to skin prep) |
| Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Graft Site | Before surgery (prior to skin preparation) and after surgery (after closing fascia) | Total bacterial counts from samples of skin flora from the graft incision site after surgery minus before surgery (prior to skin prep). |
Countries
Brazil, Chile, Germany, Singapore, United States
Participant flow
Recruitment details
Patients were enrolled between April 2006 and February 2009 at 5 centers in the United States, Europe, Asia, and Latin America.
Pre-assignment details
Of 300 patients assessed for eligibility, 7 were not allocated to treatment due to inclusion or exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions Prior to incision, surgical sites were prepared using InteguSeal\* following standard surgical preparation with povidone iodine or 0.7% available iodine in isopropyl alcohol 74% w/w. InteguSeal\* is a film-forming cyanoacrylate-based microbial skin sealant developed to decrease wound contamination by endogenous skin flora. | 146 |
| Standard Surgical Preparation Solutions Prior to incision, standard surgical preparation with povidone iodine or 0.7% available iodine in isopropyl alcohol 74% w/w. | 147 |
| Total | 293 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Did not meet inclusion/exclusion criteri | 0 | 2 |
| Overall Study | Discharged from court service | 0 | 1 |
| Overall Study | Discontinuation reason missing | 0 | 3 |
| Overall Study | Emergency care required | 0 | 1 |
| Overall Study | Withdrew consent | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Standard Surgical Preparation Solutions | InteguSeal* and Standard Surgical Preparation Solutions |
|---|---|---|---|
| Age Continuous | 63.06 years STANDARD_DEVIATION 9.28 | 62.94 years STANDARD_DEVIATION 9.97 | 63.18 years STANDARD_DEVIATION 8.53 |
| Alcohol Use No | 199 participants | 95 participants | 104 participants |
| Alcohol Use Yes | 94 participants | 52 participants | 42 participants |
| Body Mass Index (BMI) | 26.9 kg/m^2 STANDARD_DEVIATION 3.71 | 26.6 kg/m^2 STANDARD_DEVIATION 3.4 | 27.3 kg/m^2 STANDARD_DEVIATION 4 |
| Diabetes mellitus, type 1 or 2 absent | 195 participants | 98 participants | 97 participants |
| Diabetes mellitus, type 1 or 2 present | 98 participants | 49 participants | 49 participants |
| Height | 1.67 meters STANDARD_DEVIATION 0.1 | 1.66 meters STANDARD_DEVIATION 0.09 | 1.67 meters STANDARD_DEVIATION 0.1 |
| New York Heart Association (NYHA) Functional Classification Class I | 67 participants | 38 participants | 29 participants |
| New York Heart Association (NYHA) Functional Classification Class II | 134 participants | 61 participants | 73 participants |
| New York Heart Association (NYHA) Functional Classification Class III | 82 participants | 43 participants | 39 participants |
| New York Heart Association (NYHA) Functional Classification Class IV | 10 participants | 5 participants | 5 participants |
| Obesity Not obese | 233 participants | 127 participants | 106 participants |
| Obesity Obese (BMI>30.0 kg/m^2) | 60 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 44 Participants | 18 Participants | 26 Participants |
| Sex: Female, Male Male | 249 Participants | 129 Participants | 120 Participants |
| Tobacco Use no | 118 participants | 56 participants | 62 participants |
| Tobacco Use yes | 175 participants | 91 participants | 84 participants |
| Weight | 75.0 kilograms STANDARD_DEVIATION 13.3 | 73.8 kilograms STANDARD_DEVIATION 12 | 76.2 kilograms STANDARD_DEVIATION 14.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 146 | 10 / 147 |
| serious Total, serious adverse events | 6 / 146 | 8 / 147 |
Outcome results
Primary
Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Graft Site
Number of unique bacterial colony types isolated from samples of skin flora taken from the graft incision site after surgery minus before surgery (prior to skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests.
Time frame: Before surgery (prior to skin preparation) and after surgery (after closing fascia)
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Graft Site | -1.88 isolates | Standard Deviation 1.1 |
| Standard Surgical Preparation Solutions | Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Graft Site | -1.75 isolates | Standard Deviation 1 |
Comparison: The sample size determination was selected to achieve 80% power to detect an absolute 10% difference between the two treatment groups in proportion of qualitative reduction in representative skin flora, at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction.p-value: 0.359Wilcoxon-Rank Sum Test
Primary
Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Sternal Site
Number of unique bacterial colony types isolated from samples of skin flora taken from the sternal incision site after surgery minus before surgery (prior to skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests.
Time frame: Before surgery (prior to skin preparation) and after surgery (after closing fascia)
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Sternal Site | -1.34 isolates | Standard Deviation 1 |
| Standard Surgical Preparation Solutions | Change in Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-CABG - Sternal Site | -1.31 isolates | Standard Deviation 1 |
Comparison: The sample size determination was selected to achieve 80% power to detect an absolute 10% difference between the two treatment groups in proportion of qualitative reduction in representative skin flora, at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction.p-value: 0.655Wilcoxon-Rank Sum Test
Secondary
Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Graft Site
Total bacterial counts from samples of skin flora from the graft incision site after surgery minus before surgery (prior to skin prep).
Time frame: Before surgery (prior to skin preparation) and after surgery (after closing fascia)
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Graft Site | -2.42 log CFU/mL | Standard Deviation 1.3 |
| Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Graft Site | -2.31 log CFU/mL | Standard Deviation 1.2 |
p-value: 0.375Wilcoxon-Rank Sum Test
Secondary
Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Sternal Site
Total bacterial counts from samples of skin flora from the sternal incision site after surgery minus before surgery (prior to skin prep).
Time frame: Before surgery (prior to skin preparation) and after surgery (after closing fascia)
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Sternal Site | -2.14 log CFU/mL | Standard Deviation 1.4 |
| Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-CABG - Sternal Site | -1.99 log CFU/mL | Standard Deviation 1.3 |
p-value: 0.276Wilcoxon-Rank Sum Test
Secondary
Change in Bacterial Count From Pre-skin Preparation to Post-incision - Graft Site
Total bacterial counts from samples of skin flora from the graft incision site immediately after incision minus before surgery (prior to skin prep)
Time frame: Before surgery (prior to skin preparation) and immediately after incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-incision - Graft Site | -2.51 log CFU/mL | Standard Deviation 1.3 |
| Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-incision - Graft Site | -2.58 log CFU/mL | Standard Deviation 1.2 |
p-value: 0.73Wilcoxon-Rank Sum Test
Secondary
Change in Bacterial Count From Pre-skin Preparation to Post-incision - Sternal Site
Total bacterial counts from samples of skin flora from the sternal incision site immediately after incision minus before surgery (prior to skin prep)
Time frame: Before surgery (prior to skin preparation) and immediately after incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-incision - Sternal Site | -2.51 log CFU/mL | Standard Deviation 1.3 |
| Standard Surgical Preparation Solutions | Change in Bacterial Count From Pre-skin Preparation to Post-incision - Sternal Site | -2.54 log CFU/mL | Standard Deviation 1.2 |
p-value: 0.96Wilcoxon-Rank Sum Test
Secondary
Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Graft Site
Number of unique bacterial colony types isolated from samples of skin flora from the graft incision site immediately after the incision minus before surgery (prior to surgical skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests.
Time frame: Before surgery (prior to skin preparation) and immediately after incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Graft Site | -1.95 isolates | Standard Deviation 1.1 |
| Standard Surgical Preparation Solutions | Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Graft Site | -1.98 isolates | Standard Deviation 1 |
p-value: 0.788Wilcoxon-Rank Sum Test
Secondary
Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Sternal Site
Number of unique bacterial colony types isolated from samples of skin flora from the sternal incision site immediately after the incision minus before surgery (prior to surgical skin prep). Unique colonies were determined based on Gram stain, colony morphology, catalase, coagulase, or staphylococci latex agglutination and oxidase tests.
Time frame: Before surgery (prior to skin preparation) and immediately after incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Sternal Site | -1.53 isolates | Standard Deviation 0.9 |
| Standard Surgical Preparation Solutions | Change in the Number of Unique Bacterial Isolates From Pre-skin Preparation to Post-incision - Sternal Site | -1.59 isolates | Standard Deviation 1 |
p-value: 0.646Wilcoxon-Rank Sum Test
Secondary
Number of Patients With Alcohol Use, Tobacco Use, or Obesity With Surgical Site Infection (SSI)
Number of patients with risk factors of alcohol use, tobacco use, or obesity who developed an SSI at the sternal and/or graft site
Time frame: 30 days
Population: Subset of Intention to treat participants with alcohol use, tobacco use, or obesity
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Number of Patients With Alcohol Use, Tobacco Use, or Obesity With Surgical Site Infection (SSI) | 5 Participants |
| Standard Surgical Preparation Solutions | Number of Patients With Alcohol Use, Tobacco Use, or Obesity With Surgical Site Infection (SSI) | 11 Participants |
p-value: 0.024Fisher Exact
Secondary
Number of Patients With SSI at the Sternal Site and/or Graft Site
Number of patients who develop at least one surgical site infection at the sternal or graft site during the 30 day post-op follow-up period
Time frame: 30 days
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Number of Patients With SSI at the Sternal Site and/or Graft Site | 9 Participants |
| Standard Surgical Preparation Solutions | Number of Patients With SSI at the Sternal Site and/or Graft Site | 14 Participants |
p-value: 0.285Chi-squared
Secondary
Post-CABG Procedure Bacterial Count - Graft Site
Total bacterial counts from samples of skin flora of the graft incision site taken immediately following the CABG procedure.
Time frame: Post-surgery
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Post-CABG Procedure Bacterial Count - Graft Site | 0.19 log CFU/mL | Standard Deviation 0.5 |
| Standard Surgical Preparation Solutions | Post-CABG Procedure Bacterial Count - Graft Site | 0.34 log CFU/mL | Standard Deviation 0.7 |
p-value: 0.057Wilcoxon-Rank Sum Test
Secondary
Post-CABG Procedure Bacterial Count - Sternal Site
Total bacterial counts from samples of skin flora of the sternal incision site taken immediately following the CABG procedure.
Time frame: Post-surgery
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Post-CABG Procedure Bacterial Count - Sternal Site | 0.58 log CFU/mL | Standard Deviation 1 |
| Standard Surgical Preparation Solutions | Post-CABG Procedure Bacterial Count - Sternal Site | 0.83 log CFU/mL | Standard Deviation 1.1 |
p-value: 0.039Wilcoxon-Rank Sum Test
Secondary
Post-incision Bacterial Count - Graft Site
Total bacterial counts from samples of skin flora of the graft incision site taken immediately following the surgical incision
Time frame: Immediately after surgical incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Post-incision Bacterial Count - Graft Site | 0.10 log CFU/mL | Standard Deviation 0.4 |
| Standard Surgical Preparation Solutions | Post-incision Bacterial Count - Graft Site | 0.08 log CFU/mL | Standard Deviation 0.4 |
p-value: 0.512Wilcoxon-Rank Sum Test
Secondary
Post-incision Bacterial Count - Sternal Site
Total bacterial counts from samples of skin flora of the sternal incision site taken immediately following the surgical incision
Time frame: Immediately after surgical incision
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| InteguSeal* and Standard Surgical Preparation Solutions | Post-incision Bacterial Count - Sternal Site | 0.21 log CFU/mL | Standard Deviation 0.7 |
| Standard Surgical Preparation Solutions | Post-incision Bacterial Count - Sternal Site | 0.26 log CFU/mL | Standard Deviation 0.7 |
p-value: 0.348Wilcoxon-Rank Sum Test