Breast Cancer, Nonmalignant Breast Conditions
Conditions
Keywords
Bilateral breast mastectomy, Immediate tissue expanders reconstruction
Brief summary
Surgical site infection (SSI) after breast and axillary surgery occurs more often than for other clean surgical procedures. Infection in the setting of a tissue expander can be devastating and can lead to early implant loss and failed reconstruction. Surgical drains have been noted as a potential source for surgical site infections. Hypothesis: Bacteria present in surgical drains after tissue expander reconstruction may be decreased by simple and inexpensive local antiseptic interventions.
Detailed description
Surgical Site infection after breast surgical procedures occurs more frequently than for other clean surgical procedures. Considering the large numbers of patients who undergo breast-related procedures per year and the increasing use of immediate breast reconstruction with placement of tissue expanders or immediate implant reconstruction, a surgical site infection involving the implant can result in its removal and a failed reconstruction. The primary aim of the study is to determine if chlorhexidine disk application and irrigation of the drainage bulb with dilute Dakin's solution (buffered sodium hypochlorite solution)after tissue expander breast reconstruction or immediate implant reconstruction, effectively decreases rates of bacterial colonization in drain fluid compared to standard care. Methods: Patients undergoing bilateral immediate reconstruction with tissue expander placement will have one surgical site treated with standard drain care and the other treated with a drain antisepsis regimen. Drain antisepsis intervention will consist of two measures: 1) placement of a chlorhexidine sponge dressing at the drain exit site, and 2) twice daily irrigation of the drainage bulb with dilute Dakin's solution (buffered hypochlorite). All patients will undergo semiquantitative cultures of the drain bulb at one week postoperatively. This culture will be repeated at the time of drain removal, with simultaneous cultures of the fluid in the bulb as well as an internal segment of each removed drainage tube. All patients will be evaluated for clinical signs of infection and for any adverse reactions to the drain antisepsis at the follow-up visits.
Interventions
DEVICESodium hypochlorite (Dakin's Solution)
10 ml of 0.125% sodium hypochlorite (Dakin's solution) irrigation to the drainage bulb two times a day
DEVICEChlorhexidine gluconate disk
Apply one chlorhexidine disk to the intervention drain site(s) and change every three days
PROCEDUREControl
Standard drain care will be performed twice a day or three times if bulb is full and needs to be emptied. Standard drain care consists of stripping the tubing, emptying the drainage bulb, recording the volume of fluid, and cleaning the drain site with a cotton swab dipped in rubbing alcohol. The drain exit will be covered with a dry sterile gauze dressing and changed after each episode of drain care.
DEVICEOcclusive Adhesive Dressing
A chlorhexidine gluconate disk (BioPatch) covered by an occlusive adhesive dressing (Tegaderm) will be applied to the intervention drain sites and changed every three days.
Sponsors
University of California, San Francisco
Ethicon, Inc.
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* Females or males age 18-90 able to give informed consent * Undergoing bilateral mastectomy with immediate expander reconstruction or immediate implant reconstruction * May have either malignant or benign breast condition
Exclusion criteria
* Antibiotic use in the fourteen days prior to surgical date * Undergoing unilateral tissue expander reconstruction * Documented allergy to chlorhexidine gluconate * Prior radiation therapy to the breast or chest wall (ie for breast conservation or mantle radiation for Hodgkin's disease) * Documented allergy to all three of the following antibiotics: cephalosporin, trimethoprim/sulfamethoxazole, and levofloxacin * Pregnant women * Vulnerable subjects - prisoners, institutionalized individuals * Non-English speaking patients without adequate interpreter assistance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Approximately 1 Week | Approximately 1 week after surgery | Bacterial growth was defined as plate growth of 1+ or greater. Drains were removed at variable times across patients, per clinical indication. When clinically indicated, some patients did have their drains removed at the one week visit, in which case they only had one bulb fluid culture. |
| Per Drain Analysis: Drain Bulb Fluid Colonization at Approximately 1 Week | Approximately 1 week after surgery | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Surgical Site Infection Within 30 Days | Approximately 30 days after surgery | — |
| Number of Subjects With Surgical Site Infection Within 1 Year | Approximately one year after surgery | — |
| Number of Subjects With Drain Tubing Colonization at Removal | Approximately two weeks after surgery | Drain tubing colonization was defined as greater than 50 colony forming units. Drains were removed at variable timepoints based on the clinical situation. |
| Per Drain Analysis: Drain Bulb Fluid Colonization at Removal | Approximately one month after surgery | — |
| Per Drain Analysis: Drain Tubing Colonization at Removal | Approximately one month after surgery | — |
| Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Removal | Approximately 2 weeks after surgery | Bacterial growth was defined as plate growth of 1+ or greater. Drains were removed a variable times across patients, per clinical indication. A second bulb culture was obtained later than 1 week ONLY in those drains that were not removed at 1 week. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at the Mayo Clinic, Rochester, Minnesota, and the University of California, San Francisco, California. Eligible subjects were recruited prospectively from the breast surgical practices between May 2011 and June 2013.
Pre-assignment details
Six subjects did not start study therapy: One subject became a screen failure when her procedure was changed to a lumpectomy. For one subject, no Dakin's solution was available at the pharmacy. Four subjects withdrew, changing their minds about participating.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Because a paired study design was used (only bilateral procedures), each subject served as her own control. Randomization assigned which side (right or left) would receive the antisepsis interventions, and the contralateral side received standard drain care. | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Surgical Drains Fell Out at Home | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Acellular dermal matrix used (Antisepsis Side) No | 29 participants |
| Acellular dermal matrix used (Antisepsis Side) Yes | 75 participants |
| Acellular dermal matrix used (Control Side) No | 28 participants |
| Acellular dermal matrix used (Control Side) Yes | 76 participants |
| Adjuvant Radiation Therapy (Antisepsis Side) No | 97 participants |
| Adjuvant Radiation Therapy (Antisepsis Side) Yes | 7 participants |
| Adjuvant Radiation Therapy (Control Side) No | 96 participants |
| Adjuvant Radiation Therapy (Control Side) Yes | 8 participants |
| Age, Continuous | 46 years |
| American Society of Anesthesiologists (ASA) Class Class I | 19 participants |
| American Society of Anesthesiologists (ASA) Class Class II | 77 participants |
| American Society of Anesthesiologists (ASA) Class Class III | 8 participants |
| Body Mass Index | 23.8 kg/m^2 |
| Diagnosis of diabetes No | 101 participants |
| Diagnosis of diabetes Yes | 3 participants |
| Indication for Mastectomy (Antisepsis Side) Cancer | 46 participants |
| Indication for Mastectomy (Antisepsis Side) Risk-reducing | 58 participants |
| Indication for Mastectomy (Control Side) Cancer | 42 participants |
| Indication for Mastectomy (Control Side) Risk-reducing | 62 participants |
| Indication for surgery Bilateral cancer | 8 participants |
| Indication for surgery Bilateral prophylactic mastectomy | 24 participants |
| Indication for surgery Unilateral cancer with CPM | 72 participants |
| Intraoperative Fill Volume (Antisepsis Side) | 150 mL |
| Intraoperative Fill Volume (Control Side) | 150 mL |
| Maximum Drain Duration (Antisepsis Side) | 13 days |
| Maximum Drain Duration (Control Side) | 13 days |
| Neoadjuvant chemotherapy No | 72 participants |
| Neoadjuvant chemotherapy Yes | 32 participants |
| Number of Drains (Antisepsis Side) 1 | 52 participants |
| Number of Drains (Antisepsis Side) 2 | 47 participants |
| Number of Drains (Antisepsis Side) 3 | 5 participants |
| Number of Drains (Control Side) 1 | 54 participants |
| Number of Drains (Control Side) 2 | 42 participants |
| Number of Drains (Control Side) 3 | 8 participants |
| Number of Lymph Nodes Removed (Antisepsis Side) | 3 lymph nodes |
| Number of Lymph Nodes Removed (Control Side) | 4 lymph nodes |
| Operative Time | 5.1 hours |
| Region of Enrollment United States | 104 participants |
| Sex: Female, Male Female | 104 Participants |
| Sex: Female, Male Male | 0 Participants |
| Smoking within 4 weeks preoperation No | 99 participants |
| Smoking within 4 weeks preoperation Unknown | 1 participants |
| Smoking within 4 weeks preoperation Yes | 4 participants |
| Type of Mastectomy (Antisepsis Side) Nipple-sparing | 67 participants |
| Type of Mastectomy (Antisepsis Side) Skin-sparing | 37 participants |
| Type of Mastectomy (Control Side) Nipple-sparing | 68 participants |
| Type of Mastectomy (Control Side) Skin-sparing | 36 participants |
| Type of Operation (Antisepsis side) Mastectomy + axillary lymph node dissection (ALND) | 11 participants |
| Type of Operation (Antisepsis side) Mastectomy only | 58 participants |
| Type of Operation (Antisepsis side) Mastectomy + sentinel lymph node biopsy (SLNB) | 35 participants |
| Type of Operation (Control Side) Mastectomy + axillary lymph node dissection (ALND) | 11 participants |
| Type of Operation (Control Side) Mastectomy only | 61 participants |
| Type of Operation (Control Side) Mastectomy + sentinel lymph node biopsy (SLNB) | 32 participants |
| Type of Preoperative Antibiotic Cefazolin | 92 participants |
| Type of Preoperative Antibiotic Clindamycin | 6 participants |
| Type of Preoperative Antibiotic Levofloxacin | 3 participants |
| Type of Preoperative Antibiotic Vancomycin | 3 participants |
| Type of Reconstruction (Antisepsis Side) Direct-to-implant | 9 participants |
| Type of Reconstruction (Antisepsis Side) Tissue expander | 95 participants |
| Type of Reconstruction (Control Side) Direct-to-implant | 9 participants |
| Type of Reconstruction (Control Side) Tissue expander | 95 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 104 | 6 / 104 |
| serious Total, serious adverse events | 0 / 104 | 0 / 104 |
Outcome results
Primary
Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Approximately 1 Week
Bacterial growth was defined as plate growth of 1+ or greater. Drains were removed at variable times across patients, per clinical indication. When clinically indicated, some patients did have their drains removed at the one week visit, in which case they only had one bulb fluid culture.
Time frame: Approximately 1 week after surgery
Population: Analysis was modified intent-to-treat (IIT); subjects who withdrew or were screen failures before study intervention were excluded. All patients who completed were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Approximately 1 Week | Antisepsis Side | 10 participants |
| Entire Study Population | Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Approximately 1 Week | Control Side | 21 participants |
Comparison: Antisepsis and Control sides were compared.p-value: 0.02McNemar
Primary
Per Drain Analysis: Drain Bulb Fluid Colonization at Approximately 1 Week
Time frame: Approximately 1 week after surgery
Population: Analysis was modified intent-to-treat (IIT); subjects who withdrew or were screen failures before study intervention were excluded. All patients who completed were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Per Drain Analysis: Drain Bulb Fluid Colonization at Approximately 1 Week | Antisepsis side n=157 drains | 11 drains |
| Entire Study Population | Per Drain Analysis: Drain Bulb Fluid Colonization at Approximately 1 Week | Control side n=160 drains | 25 drains |
Comparison: Antisepsis and Control sides were compared. Unadjusted p-value from generalized linear mixed effect model accounting for correlation among multiple drains from the same patient.p-value: 0.02Mixed Models Analysis
Comparison: Antisepsis and Control sides were compared. P-value from generalized linear mixed effect model accounting for correlation among multiple drains from the same patient. P-value was adjusted for side- and drain-specific variables: indication (cancer or prophylaxis), operation (mastectomy only, mastectomy+SLNB, mastectomy +ALND), and drain duration.p-value: 0.02Mixed Models Analysis
Secondary
Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Removal
Bacterial growth was defined as plate growth of 1+ or greater. Drains were removed a variable times across patients, per clinical indication. A second bulb culture was obtained later than 1 week ONLY in those drains that were not removed at 1 week.
Time frame: Approximately 2 weeks after surgery
Population: Analysis was modified intent-to-treat (IIT). Reported here only in those subjects where drain removal was later than primary endpoint collection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Removal | Antisepsis Side | 14 participants |
| Entire Study Population | Number of Subjects With Drain Bulb Fluid Bacterial Colonization at Removal | Control Side | 28 participants |
Comparison: Antisepsis and Control sides were compared.p-value: 0.003McNemar
Secondary
Number of Subjects With Drain Tubing Colonization at Removal
Drain tubing colonization was defined as greater than 50 colony forming units. Drains were removed at variable timepoints based on the clinical situation.
Time frame: Approximately two weeks after surgery
Population: Analysis was modified intent-to-treat; subjects who withdrew or were screen failures before study intervention were excluded. All patients who completed were included in the analysis. 2 subjects missed endpoint due of protocol deviation or discontinuation, and 2 had the sterility of their drain tubing compromised by external exposures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Number of Subjects With Drain Tubing Colonization at Removal | Antisepsis Side | 0 participants |
| Entire Study Population | Number of Subjects With Drain Tubing Colonization at Removal | Control Side | 6 participants |
Comparison: Antisepsis and Control sides were compared.p-value: 0.03McNemar
Secondary
Number of Subjects With Surgical Site Infection Within 1 Year
Time frame: Approximately one year after surgery
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Number of Subjects With Surgical Site Infection Within 1 Year | Antisepsis Side | 3 participants |
| Entire Study Population | Number of Subjects With Surgical Site Infection Within 1 Year | Control Side | 6 participants |
Comparison: Antisepsis and Control sides were compared.p-value: 0.45McNemar
Secondary
Number of Subjects With Surgical Site Infection Within 30 Days
Time frame: Approximately 30 days after surgery
Population: Analysis was modified intent-to-treat (IIT); subjects who withdrew or were screen failures before study intervention were excluded. All patients who completed were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Number of Subjects With Surgical Site Infection Within 30 Days | Antisepsis Side | 0 participants |
| Entire Study Population | Number of Subjects With Surgical Site Infection Within 30 Days | Control Side | 4 participants |
Comparison: Antisepsis and Control sides were compared.p-value: 0.13McNemar
Secondary
Per Drain Analysis: Drain Bulb Fluid Colonization at Removal
Time frame: Approximately one month after surgery
Population: Analysis was modified intent-to-treat (IIT). Reported here only in those subjects where drain removal was later than primary endpoint collection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Per Drain Analysis: Drain Bulb Fluid Colonization at Removal | Antisepsis side, n=85 drains | 14 drains |
| Entire Study Population | Per Drain Analysis: Drain Bulb Fluid Colonization at Removal | Control side, n=88 drains | 33 drains |
Comparison: Antisepsis and Control sides were compared. Unadjusted p-value from generalized linear mixed effect model accounting for correlation among multiple drains from the same patient.p-value: 0.003Mixed Models Analysis
Comparison: Antisepsis and Control sides were compared. P-value from generalized linear mixed effect model accounting for correlation among multiple drains from the same patient. P-value was adjusted for side- and drain-specific variables: indication (cancer or prophylaxis), operation (mastectomy only, mastectomy+SLNB, mastectomy +ALND), and drain duration.p-value: 0.003Mixed Models Analysis
Secondary
Per Drain Analysis: Drain Tubing Colonization at Removal
Time frame: Approximately one month after surgery
Population: Analysis was modified intent-to-treat; subjects who withdrew or were screen failures before study intervention were excluded. All patients who completed were included in the analysis. 2 subjects missed endpoint due of protocol deviation or discontinuation, and 2 had the sterility of their drain tubing compromised by external exposures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Entire Study Population | Per Drain Analysis: Drain Tubing Colonization at Removal | Antisepsis side, n=151 drains | 0 drains |
| Entire Study Population | Per Drain Analysis: Drain Tubing Colonization at Removal | Control side, n=154 | 6 drains |
Comparison: Antisepsis and Control sides were compared. Due to zero events in the antisepsis side for this endpoint, p-value was derived from likelihood-ratio test comparing the intercept only model to the model with intercept and treatment side included.p-value: 0.004Likelihood-ratio test