Vanguard: Topical Vancomycin for Neurosurgery Wound Prophylaxis
Study Details
Study Description
Brief Summary
This study is a collaboration between New York Presbyterian (NYP)-Columbia and NYP-Cornell that seeks to evaluate the use of topical vancomycin and its reduction on surgical site infection (SSI) in neurosurgical procedures. Adult patients undergoing neurosurgery at either institution will be eligible for participation in this randomized control trial. Patients randomized to the treatment group will receive 2g of vancomycin applied as a powder or paste to the wound site and/or bone flap. Subjects in the control group will receive the current standard of care without topical vancomycin. All subjects will undergo swabbing of the anterior nares and the surgical site prior to surgery, once 10-14 days following the operation and 90 days following the operation. The primary outcome measure will be surgical site infection, assessed daily throughout the hospital stay, at the first follow-up visit, and by telephone at 14-30 days and 90 days (+/- 7 days). Secondary outcomes will include length of hospital stay, length of intensive care stay, rate of reoperation and patient mortality. In addition, systemic vancomycin levels will be assessed at 6 hours and 20 hours postoperatively in each patient. Patients who have an external ventricular drain in place will have vancomycin levels assessed daily. In patients who have cranial drains placed, vancomycin concentrations will be analyzed from daily in wound drainage. Skin and nasal flora will be analyzed to assess the impact of topical vancomycin on the patient microbiome. Although there has been a decrease in the incidence of infections following craniotomy secondary to prophylactic intravenous antibiotics, proper sterile techniques, and other interventions, SSIs continue to significantly impact morbidity, mortality, and cost burden. Although never studied in neurosurgical procedures other than instrumented spine, the application of topical vancomycin to the surgical site prior to wound closure has demonstrated a reduction in SSIs in spine, cardiac and ophthalmologic procedures. The benefits of using prophylactic vancomycin topically, as opposed to intravenously, include reduced systemic levels of the drug, and therefore, a decreased probability of adverse events related to the drug, such as inducing resistance among the native flora. The investigators propose a single-blinded randomized control trial to evaluate the effectiveness of topical vancomycin in reducing SSIs rates following neurosurgical procedures.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
Surgical-site infections (SSIs) occur in up to 500,000 patients per year in the United States. Patients with SSIs require significantly longer hospital stays and higher health care expenditures. In fact, it is estimated that SSIs are responsible for almost 4 million excess hospital days and billions of dollars in added hospital charges every year. Additionally, SSIs are a significant source of morbidity and mortality for surgical patients. Thus, prompt and definitive measures are necessary in order to redress this significant public health concern. Over the past few decades, the implementation of a number of preventative measures-including improved techniques in pre-operative skin antisepsis and antibiotic prophylaxis-have led to significant reductions in the rate of SSIs. Studies have demonstrated that approximately half of all SSIs are preventable with the proper use of prophylactic antibiotics. Despite these dramatic improvements, SSIs remain a tremendous burden on the healthcare system. Our unpublished analysis of the National Inpatient Sample (NIS) in 2010 identified 117,000 craniotomies with a 2.4% rate of infection and 1.37% rate of Methicillin-resistant Staphylococcus aureus (MRSA)-associated infection. Extrapolating to the full national population, there were 585,000 craniotomies and 14,040 post-operative infections. Published series report the rate of infection in intracranial neurosurgery to range from 1% to as high as 11%. This rate varies depending on the presence of hardware, prior radiotherapy, procedure duration, re-operation, and the presence of a CSF leak. The 30-day outcome associated with SSI following craniotomy was recently reported to be a minor disability in 12.8%, major disability in 7.7% and death in 5.1%. The financial burden of nosocomial infection in neurosurgery makes up a disproportionate component of the total national cost burden. A study of nosocomial infection in the US in 1995 estimated a per-patient cost of $2100 and a total cost of $4.5 billion while a recent British study focusing on post-craniotomy SSI identified a per-SSI cost of £9283, or $14,166. Given the tremendous potential for lifelong morbidity and mortality as a result of cranial SSIs, further reductions in the rate of SSI would be essential for the benefit of neurosurgical patients, as well as for the healthcare system as a whole.Topical formulations of vancomycin offer the possibility of direct application to the surgical wound, with minimal additional systemic drug exposure. Adjunctive vancomycin powder applied topically to surgical wound edges has been shown to significantly lower the SSI rate in both cardiothoracic surgery and spinal surgery. Importantly, laboratory analyses of blood and wound drainage samples from patients treated with vancomycin powder have demonstrated high vancomycin concentrations in the surgical wound, and simultaneously low drug concentrations in the peripheral blood, thereby confirming minimal systemic absorption in the setting of enhanced protection of the surgical site. Furthermore, there have been no reports of an increased rate of drug-related complications with the addition of vancomycin powder to standard antibiotic prophylaxis regimens.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Topical Vancomycin Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis |
Drug: Vancomycin
Topically applied powder and paste to surgical site at time of closure.
Other Names:
|
| No Intervention: Standard of Care Control group, receive standard of care only |
Outcome Measures
Primary Outcome Measures
- Any Surgical-site Infection as Evidenced by Surgeon or Attending Physician Diagnosis, or Signs and Symptoms of Infection Assessed by Phone Call Interview or at In-office Follow-up Consultation [30 days & 90 days (+/- 7 days) postoperatively]
Classified as superficial incisional, deep incisional, or organ/space (intradural) infection
- Number of Subjects That Reported Any Surgical-site Infections [30 days & 90 days (+/- 7 days) postoperatively]
As evidenced by surgeon or attending physician diagnosis, or signs and symptoms of infection assessed by phone call interview or at in-office follow-up consultation. Classified as superficial incisional, deep incisional, or organ/space (intradural) infection.
Secondary Outcome Measures
- Serum Vancomycin Levels [6-20 hours post-operatively]
Vancomycin levels in serum will be tested after surgery, any additional fluid collections, but if and only if clinically indicated. The data is collected post-operative and will not be analyzed until the end of the study with another collaborator using Statewide Planning and Research Cooperative System (SPARCS) and New York State (NYS) datasets.
- Development of Previously Undetected Vancomycin Resistance [90 days postoperatively]
Microbial swabs will be obtained by the clinical coordinator preoperatively, post-operatively, at 10-14 days and at 90 days. Staph aureus isolates from mannitol growth will be tested for vancomycin resistance, comparing preoperative baseline and postoperative timepoints for development of increased vancomycin resistance. The data is collected post-operative and will not be analyzed until the end of the study with another collaborator using SPARCS and NYS datasets.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Adult (18+) neurosurgical procedure (ie.Craniotomy, Craniectomy, and Cranioplasty)
Exclusion Criteria:
-
Creatinine > 1.50 mg/dL on admission
-
Vancomycin allergy (documented or self-reported)
-
Evidence of infection at or near the planned surgical site
-
No planned dural or dural-substitute closure
-
Spinal instrumentation (topical vancomycin is already standard of care)
-
No surface area to apply:Carotid endarterectomy, MRI-guided laser ablation
-
Trans-sphenoidal approach
-
Acoustic neuroma resection
-
Surgeon preference for or against use in the given procedure
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Columbia University Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Columbia University
- Agency for Healthcare Research and Quality (AHRQ)
- Cornell University
- Icahn School of Medicine at Mount Sinai
Investigators
- Principal Investigator: E. Sander Connolly, M.D., Columbia University
Study Documents (Full-Text)
More Information
Publications
None provided.- AAAN3703
- 1R01HS022903-01
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Topical Vancomycin | Standard of Care |
|---|---|---|
| Arm/Group Description | Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis Vancomycin: Topically applied powder and paste to surgical site at time of closure. | Control group, receive standard of care only |
| Period Title: Overall Study | ||
| STARTED | 552 | 551 |
| COMPLETED | 484 | 489 |
| NOT COMPLETED | 68 | 62 |
Baseline Characteristics
| Arm/Group Title | Topical Vancomycin | Standard of Care | Total |
|---|---|---|---|
| Arm/Group Description | Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis Vancomycin: Topically applied powder and paste to surgical site at time of closure. | Control group, receive standard of care only | Total of all reporting groups |
| Overall Participants | 484 | 489 | 973 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
54.1
(16.1)
|
53.3
(17.0)
|
53.7
(16.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
276
57%
|
280
57.3%
|
556
57.1%
|
| Male |
208
43%
|
209
42.7%
|
417
42.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
50
10.3%
|
43
8.8%
|
93
9.6%
|
| Not Hispanic or Latino |
403
83.3%
|
403
82.4%
|
806
82.8%
|
| Unknown or Not Reported |
31
6.4%
|
43
8.8%
|
74
7.6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
0.2%
|
1
0.2%
|
2
0.2%
|
| Asian |
19
3.9%
|
24
4.9%
|
43
4.4%
|
| Native Hawaiian or Other Pacific Islander |
3
0.6%
|
1
0.2%
|
4
0.4%
|
| Black or African American |
39
8.1%
|
33
6.7%
|
72
7.4%
|
| White |
337
69.6%
|
339
69.3%
|
676
69.5%
|
| More than one race |
18
3.7%
|
18
3.7%
|
36
3.7%
|
| Unknown or Not Reported |
67
13.8%
|
73
14.9%
|
140
14.4%
|
Outcome Measures
| Title | Any Surgical-site Infection as Evidenced by Surgeon or Attending Physician Diagnosis, or Signs and Symptoms of Infection Assessed by Phone Call Interview or at In-office Follow-up Consultation |
|---|---|
| Description | Classified as superficial incisional, deep incisional, or organ/space (intradural) infection |
| Time Frame | 30 days & 90 days (+/- 7 days) postoperatively |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Topical Vancomycin | Standard of Care |
|---|---|---|
| Arm/Group Description | Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis Vancomycin: Topically applied powder and paste to surgical site at time of closure. | Control group, receive standard of care only |
| Measure Participants | 484 | 489 |
| Subject visited doctor and received antibiotics |
18
3.7%
|
19
3.9%
|
| Subject reports any possible symptom of surgical site infection |
344
71.1%
|
355
72.6%
|
| Positive skin culture or hospital readmission for surgical site infection |
5
1%
|
4
0.8%
|
| Title | Number of Subjects That Reported Any Surgical-site Infections |
|---|---|
| Description | As evidenced by surgeon or attending physician diagnosis, or signs and symptoms of infection assessed by phone call interview or at in-office follow-up consultation. Classified as superficial incisional, deep incisional, or organ/space (intradural) infection. |
| Time Frame | 30 days & 90 days (+/- 7 days) postoperatively |
Outcome Measure Data
| Analysis Population Description |
|---|
| Out of 1103 enrolled subjects, only 973 subjects completed the study and their data have been analyzed and presented here. |
| Arm/Group Title | Topical Vancomycin | Standard of Care |
|---|---|---|
| Arm/Group Description | Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis Vancomycin: Topically applied powder and paste to surgical site at time of closure. | Control group, receive standard of care only |
| Measure Participants | 484 | 489 |
| Number [participants] |
344
71.1%
|
355
72.6%
|
| Title | Serum Vancomycin Levels |
|---|---|
| Description | Vancomycin levels in serum will be tested after surgery, any additional fluid collections, but if and only if clinically indicated. The data is collected post-operative and will not be analyzed until the end of the study with another collaborator using Statewide Planning and Research Cooperative System (SPARCS) and New York State (NYS) datasets. |
| Time Frame | 6-20 hours post-operatively |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Development of Previously Undetected Vancomycin Resistance |
|---|---|
| Description | Microbial swabs will be obtained by the clinical coordinator preoperatively, post-operatively, at 10-14 days and at 90 days. Staph aureus isolates from mannitol growth will be tested for vancomycin resistance, comparing preoperative baseline and postoperative timepoints for development of increased vancomycin resistance. The data is collected post-operative and will not be analyzed until the end of the study with another collaborator using SPARCS and NYS datasets. |
| Time Frame | 90 days postoperatively |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 90 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Topical Vancomycin | Standard of Care | ||
| Arm/Group Description | Treatment group, receive 2 g topical vancomycin hydrochloride (1 g applied as powder, 1 g mixed with sterile solution and applied as paste) at the time of closure, in addition to the standard of care for wound prophylaxis Vancomycin: Topically applied powder and paste to surgical site at time of closure. | Control group, receive standard of care only | ||
All Cause Mortality |
||||
| Topical Vancomycin | Standard of Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/552 (0.9%) | 6/551 (1.1%) | ||
Serious Adverse Events |
||||
| Topical Vancomycin | Standard of Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 49/552 (8.9%) | 65/551 (11.8%) | ||
| Cardiac disorders | ||||
| Left Ventricular Thrombus | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Pericarditis | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Hearing loss | 4/552 (0.7%) | 4 | 7/551 (1.3%) | 7 |
| Endocrine disorders | ||||
| Pancreatic Necrosis | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Gastrointestinal disorders | ||||
| Gastrointestinal Changes | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| General disorders | ||||
| Death | 5/552 (0.9%) | 5 | 6/551 (1.1%) | 6 |
| Unplanned Medical Visit | 21/552 (3.8%) | 22 | 37/551 (6.7%) | 37 |
| Bleeding at drain site | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Gait instability | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Chest Pain | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Pain | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Epidural Abscess | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Immune system disorders | ||||
| Allergy Symptoms | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Infections and infestations | ||||
| Surgical Site Infection | 4/552 (0.7%) | 4 | 4/551 (0.7%) | 4 |
| Urinary Tract Infeciton | 1/552 (0.2%) | 1 | 3/551 (0.5%) | 3 |
| Sepsis | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Discharge | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Nervous system disorders | ||||
| Vision Impairment | 1/552 (0.2%) | 1 | 2/551 (0.4%) | 2 |
| Facial Sensory Loss | 1/552 (0.2%) | 1 | 1/551 (0.2%) | 1 |
| Meningitis | 1/552 (0.2%) | 1 | 1/551 (0.2%) | 1 |
| Dysarthria/Dysphagia | 0/552 (0%) | 0 | 3/551 (0.5%) | 3 |
| Hemiparesis | 1/552 (0.2%) | 1 | 3/551 (0.5%) | 3 |
| Encephalopathy | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Cognitive Impairment | 2/552 (0.4%) | 2 | 2/551 (0.4%) | 2 |
| Stroke/Cerebrovasular accident | 3/552 (0.5%) | 3 | 2/551 (0.4%) | 2 |
| Drop foot | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Seizure | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Pneumocephalus | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Psychiatric disorders | ||||
| Hallucination | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
| Renal and urinary disorders | ||||
| Hematuria | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Aspiration Pneumonia | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Hypoxia | 0/552 (0%) | 0 | 1/551 (0.2%) | 1 |
| Vascular disorders | ||||
| Deep Vein Thrombosis | 3/552 (0.5%) | 3 | 1/551 (0.2%) | 1 |
| Hematoma | 1/552 (0.2%) | 1 | 1/551 (0.2%) | 1 |
| Pulmonary Embolism | 1/552 (0.2%) | 1 | 0/551 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Topical Vancomycin | Standard of Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 121/552 (21.9%) | 119/551 (21.6%) | ||
| Ear and labyrinth disorders | ||||
| Hearing Change | 24/552 (4.3%) | 26 | 26/551 (4.7%) | 27 |
| General disorders | ||||
| Unplanned Medical Visit | 35/552 (6.3%) | 38 | 26/551 (4.7%) | 30 |
| Immune system disorders | ||||
| Allergy Symptoms | 32/552 (5.8%) | 32 | 33/551 (6%) | 33 |
| Metabolism and nutrition disorders | ||||
| Gastrointestinal changes | 30/552 (5.4%) | 33 | 34/551 (6.2%) | 36 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. E. Sander Connolly Jr. |
|---|---|
| Organization | Columbia University Irving Medical Center |
| Phone | 2123054118 |
| esc5@cumc.columbia.edu |
- AAAN3703
- 1R01HS022903-01