Clinical trial NCT03432858
Conditions: Carpal Tunnel Syndrome
Keywords: Endoscopic Carpal Tunnel Release Prophylactic Antibiotics
Sponsor: WellSpan Health
Start date: 2018-05-17; Completion date: 2020-12-14
Enrollment: 184 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a clinical trial to determine how effective antibiotics administered prior to endoscopic carpal tunnel release surgery are in preventing surgical site infections.

Detailed description:
Study participants will be randomized to a prophylactic IV antibiotic treatment arm (Vancomycin or Cefazolin) or a placebo IV saline solution. Subjects will be monitored following surgery for surgical site infections.

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Vancomycin intervention 2: Cefazolin intervention 3: Saline Solution
Intervention descriptions: intervention 1: Vancomycin - 1-gram dosing intervention 2: 2-gram dosing for patients \<120 kg 3-gram dosing for patients 120 kg or greater intervention 3: Placebo

Protocol documents:
Prot_SAP_000.pdf: 
 
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Preoperative Antibiotics for Carpal Tunnel 
Release Surgery 
 
NCT 03432858 
 
Endoscopic Carpal Tunnel Release, Infection Incidence, and Prophylactic 
Antibiotics: Indicated or kick the habit? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Document Date: October 10, 2018 


 
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Title: Endoscopic Carpal Tunnel Release, Infection Incidence, 
and Prophylactic Antibiotics: Indicated or Kick the Habit? 
 
Version:  1.6  
 
Local Principal Investigator:  
Richard Trevino III M.D. 
 
WellSpan Orthopedics – Apple Hill 
 
25 Monument Rd #290, York, PA 
17403 
Phone: (717) 812-4090 
Email: rtrevino@wellspan.org 
 
Co-investigators: 
 
 
Michael Corum D.O. 
WellSpan Orthopedics – Apple Hill 
 
25 Monument Rd #290, York, PA 
17403 
Phone: (717) 812-4090 
Email: mcorum@wellspan.org 
 
Derek Hayden D.O. 
The Orthopedic Residency of York 
WellSpan – York Hospital 
1001 S. George St.  York, PA 17403 
Phone: (801) 669-4447 
Email: dhayden@wellspan.org  
 
Protocol 
 
A. Background  
 
Each year, one million adults in the U.S.A are diagnosed with carpal tunnel 
syndrome (CTS) with 500,000 carpal tunnel release (CTR) procedures.  
Previous analyses have shown very low rates of surgical site infections (SSI) 
overall2,10 with incidence rates of 0.25-0.77% without or 0.21-0.47% with 
surgical prophylactic antibiotics, but no statistical significance.1,2,9  These 
include populations typically considered “high risk” such as those with 
diabetes mellitus, or history of total joint arthroplasty.2,3  Despite both 
American and international current literature demonstrating low incidence of 


 
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infection in all types of CTR, and recommendations to discontinue habitual 
use of preoperative antibiotics in clean hand surgery, the behavior is still 
very prevalent with 30-60% of hand surgeons still prescribing either 
sometimes or all the time prior to CTR.2,7,9,11,12  Only 2% of British hand 
surgeons prescribe prophylactic antibiotics before CTR.  In Canada CTR 
surgery is considered minor, even being performed routinely in the clinical 
office setting, and all without prescribing antibiotics prophylactically.5  
Endoscopic carpal tunnel release (ECTR) procedures are becoming more 
common, and while current evidence supports no significant increased rates 
of complications, without direct visualization and hemostasis there is 
potential for hematoma vulnerable to infection.  While there is some 
appropriately powered,12 prospective8,12 level I evidence regarding the use of 
prophylactic preoperative antibiotics in carpal tunnel surgery in general, to 
our knowledge there are none specifically investigating incidence of SSI 
with and without antibiotics after ECTR. 
 
B. Objective(s) 
 
Establish level I evidence regarding 
• whether prophylactic antibiotics reduce the incidence of 
infection in ECTR 
 
C. Study design 
 
• Procedures by fellowship-trained hand surgeons.   
• Prospective, randomized, and double blinded.   
o RANDOMIZATION:  Participants will be randomly assigned 
to 1 of 2 groups: 1) Weight-based Ancef (or 1 g of vancomycin 
if penicillin/cephalosporin allergic) within 30 minutes of 
incision; or 2) placebo IV of normal saline. 
o BLINDING:  Neither surgeon, nor investigators, nor patient 
will know who did or did not receive antibiotics until the end of 
the project.  Randomization generator will be utilized by Emig 
Research Center associate to create a master copy, with 
subsequent sealed copies maintained at Emig Research Center, 
with Orthopaedic Residency Research Coordinator (Chelsea), 
and the WSRH pharmacy.   


 
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The patient number (P#) list will be held by the preoperative 
surgical scheduler, who will not participate in data collection 
nor follow-up.   
The corresponding decoder key of P# with associated 
randomized number will be held by WSRH Pharmacy for 
collaboration to formulate the indicated antibiotic or placebo 
solutions preoperatively. 
o PRIMARY OUTCOMES: Determine proportion of patients 
with SSI in antibiotic versus placebo group.  Subjects follow-up 
over six weeks with primary outcomes being (1) “any 
supplemental intervention” (i.e. additional wound care, 
antibiotics, or revision surgery.); and (2) declaration of 
“complete” healing by six weeks post-operative. 
• 2 weeks - clinical wound check.  
• 6 weeks – clinical assessment for completion of 
wound healing.  
• At each visit the attending physician will designate 
as “infected” or “not infected” and will be allowed 
to treat each patient accordingly.  Designations 
will be based on either: 
o Clinician experience   
▪ Considerations include but are not 
limited to painful incision, erythema, 
drainage, or wound dehiscence. 
o Culture confirmed 
▪ deep infections 
 
• Wounds designated “infected” by the treating 
surgeon will be sub-divided into: 
o Superficial (Surface only) 
▪ Treatment with local wound care 
▪ Oral antibiotics only 
o Deep 
▪ IV antibiotics only 
▪ Surgical Irrigation & Debridement 
and IV antibiotics. 
o SECONDARY OUTCOMES: 
▪ Demographic information as well as comorbidities such 
as: acuity of CTS, time from last cortisone injection, 
diabetes2, smokers, COPD, anemia, peripheral artery 
disease, history of arthroplasty3, valvular disease, and 


 
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dual or single incision ECTR will be noted for secondary 
outcome correlations. 
o DURATION:  By current estimates of 10 CTRs per week, this 
would require 65 weeks, with another 6 weeks to complete 
observations of the patients.   
o PROCEDURE:  Dual or single-incision endoscopic carpal 
tunnel release with steri-strip closure and simple sterile 
dressing, without immobilization. 
o WOUND CARE & ACTIVITY:  Non-weight bearing on 
affected extremity until 2 week follow-up appointment.  May 
shower post-operative day 4, but no submersion.  5 lb. weight 
restriction for 2 weeks, then 10 lbs for 3 weeks.  No physical 
therapy. 
 
D. Study population and recruitment methods  
 
• From the investigator’s private clinical practices, all those who meet 
criteria for carpal tunnel release will be offered to participate in the 
study.  
 
E. Inclusion and exclusion criteria 
 
o INCLUSIONS:  All patients who meet high probability (>12 points) on the 
Carpal Tunnel-6 (CTS-6) diagnostic aide and recommendation for carpal 
tunnel release who are capable of giving informed consent, or their legal 
representative on the patients behalf.  
o EXCLUSIONS:  Patients allergic to both penicillin/cephalosporins and 
vancomycin.  Patients immobilized with splint or cast or receiving formal 
physical therapy in initial 6 weeks after ECTR.  Children under the age of 18 
years old.  Patients or their legal representatives who decline the invitation for 
participation.   
o VULNERABLE POPULATIONS:  Pregnant females and prisoners will be 
treated with equal and safe fairness and randomization as other participants, 
both pre-procedure as well as post-procedure, due to the double-blinded 
nature of the antibiotic administration.  They will stand to benefit from the 
investigators clinical suspicions for infection without potential conflict of 
interest with study outcomes. 
 
 
 


 
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F. Role of subjects 
 
• Participants will agree to follow-up at 2 and 6 weeks in the clinic, as 
is already standard of care.   
• Participants will be asked to notify providers if concern for or signs of 
infection arise. 
 
G. Research procedures 
 
• Patient identified with score > 12 (80% probability) on the CTS-6 and 
recommended CTR:  (http://www.orthoguidelines.org/ctsdiagnosis)6 
o Symptoms predominantly in medial nerve innervated digits 
o Nocturnal numbness 
o Thenar atrophy and/or weakness 
o Positive phalen test 
o Positive tinel sign 
o Loss of 2-point discrimination 
• Surgeon will discuss risks, benefits, and alternatives to surgical 
intervention. 
• Patients who elect to proceed to scheduling will be invited to 
participate in the study and informed consent will be obtained prior to 
seeing surgical scheduler. 
o For those who decline participation, they will be directed to 
scheduling without tardiness or punishment. 
• After scheduling surgery, the surgical coordinator will place a patient 
study number (P# ie. P1, P2, P3, P4…) sticker on the patients surgical 
consent and participation consent and these will be scanned into the 
Epic Electronic Medical Record (EMR) under “Media – Study: 
ECTR” 
Patient will be “tagged” with a study tag on their record banner for 6 
weeks. 
Patient will be added to “ECTR & ABX” custom patient list. 
• A “miscellaneous order” to pharmacy will be placed in the Day of 
Surgery orders indicating need to blind the antibiotic solution as well 
as the P#. 
• Pharmacists at WellSpan Surgical & Rehabilitation Hospital will 
possess a copy correlating randomization numbers to each P# with 
instruction to formulate a placebo bag of normal Saline for all ODD 
numbers, or an infusion of IV antibiotics (Ancef or Vancomycin for 


 
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PCN or Cephalosporin allergic) for all EVEN numbers on the day of 
surgery.  
-Example- 
Patients p1,p4, and p5 (Even) receive antibiotic. 
Patients p2, and p3 (Odd) receive placebo. 
 
 
• On the day of surgery, blinding will continue with appropriately 
patient labeled IV bag without identifying markers of content, to be 
administered within 30 minutes of surgical incision. 
• Surgical prep will be with chlorhexidine gluconate scrub and standard 
sterile draping and technique. 
• Patients will undergo routine procedure with dual-or-single incision, 
single nylon closure, and simple adhesive steri-strip cover, without 
immobilization. 
• Wound will be visually evaluated at 2 & 6 week follow-up 
appointments  
o Activity limitations will include: 
▪ 5 lbs maximum for first two weeks 
▪ 10 lbs maximum for for two to six weeks 
▪ followed by “no restrictions” at 6 week appointment. 
• After the 6 week appointment of every 25th patient, investigators may 
“break the seal” and insert patient information from the prior 25 
patients into protected collection data tables for final evaluation at 
study completion. 
 
H. Data to be utilized 
• Demographic information 
• Medical comorbidities and history from clinic notes and Epic EMR. 
• Excel Spreadsheet with de-identified data collection 
 


 
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I. Data analysis 
• POWER:  Statistical significance would require n= 92 split evenly 
between trial and control; but clinical significance requires greater 
numbers due to the low incidence (0.25%-1.5% in the retrospective 
literature.)8,9   
o Our goal was calculated using the median incidence of 0.40%,5 
for a calculated power of n=642 split evenly between trial and 
control.  
• STATISTICAL ANALYSES:   
o Data will be analyzed using the statistical analysis program, 
SPSS. Most analysis will be completed by scientific support 
staff of the EMIG Research Center. Analysis will include 
frequency and percent determinations for all categorical 
parameters and mean and standard deviations for all continuous 
parameters. Appropriate statistical tests will be employed to 
determine any statistical differences or associations between 
groups or subgroups once they are identified, which may 
involve chi-square, ANOVA, regression, or independent sample 
t-testing. 
 
J. Risks and risk management 
• Patients will not be pressured into participation. 
• Grant funding will cover the cost of study drug to which patients are 
assigned. Patients and/or patient insurance will not be responsible for 
the cost of the study drug.  more than the current intermittent costs of 
occasional antibiotic use. 
• Insurances will be billed as usual for all other ESCR surgical costs.  
• Self-pay patients will be treated equally with insured patients.  
• The risk of disruption to patient life, work, or social risk are low since 
this protocol allows for appropriate intervention at all points along the 
patients 6 week course. 
• An interim data analysis will occur beginning at patient number 25 to 
ensure that study procedures are not causing harm. The data analysis 
will be conducted by the research associate. The co-investigator will 
review the results, and the PI will determine if it is safe to continue 
the study.  
K. Benefits 
• Study patients are not expected to directly benefit from participation. 


 
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• Patient and societal benefits will be related to surgeons doing our part 
to appropriately manage antibiotic stewardships, and decrease risks of 
antibiotic-resistant organisms. 
• Professional benefits would include support for decisions to eliminate 
unnecessary antibiotic prophylaxis in clean hand surgery; OR 
establish the risks and utility of ECTR and antibiotics compared to 
traditional surgery and preoperative protocols. 
• Economic implications include: 
o 500,000 procedures yearly with around 165,000 receiving 
antibiotics preoperatively, at estimated $50/2grams Cephazolin 
(or $150/1g Vancomycin), could save $8,745,000 yearly 
nationally (est. with Cephazolin). 
o Antibiotics are expected within 30 minutes of incision, and will 
occasionally delay incision in the operating room while the 
antibiotic is administered.  Estimated costs for OR function 
range from $20-60 per minute.  Thus even a 3 minute delay for 
rapid IV infusion, during a 15 minute procedure, wastes another 
$60-180 per procedure. 
o Up to $330 extra cost per procedure for administration of a 
potentially unnecessary treatment. 
 
L. Compensation / incentives and research-related costs 
• Compensations/Incentives: None 
• Costs:  Grant funding has been secured through Lake Erie College of 
Osteopathic Medicine (LECOM) to cover the cost of IV saline and 
antibiotics to avoid additional costs to the patient. Research time and 
product will be supplied by the primary and co-investigators and the 
Orthopaedic Surgery Residency research fund. 
 
M. Alternative procedures 
• Potential subjects are not required to participate in the study and 
refusing to do so will not affect the quality of their treatment. 
 
N. Research materials, records, and confidentiality 
• All patient records will be obtained through the secure WellSpan 
Health EMR (Epic). 


 
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• Information will be stored external to the system in a non-identifiable 
manner with a P# assigned to individuals on password encrypted 
hospital and private computers in an Excel spreadsheet. 
• No patient information will be accessed outside of typical patient care 
unless a signed HIPAA authorization form for participation in the 
study is in the patient record. 
 
O. Subject informed consent  
• CONSENT:  According to both Federal and State of Pennsylvania 
law, the surgeon of record will be authorized and trained to provide 
and obtain informed consent in writing at the preoperative visit. 
 
P. Intended use of research 
• Submission of abstracts to national conferences for posters and 
journals for manuscripts 
• Submission to Residents’ Research Day 
  
Q. Delineation of resources required to conduct the study 
• Emig Research center 
• Orthopaedic Residency research coordinator 
• Statisticians 
• Fellowship-trained Hand Surgeons 
• Hand Surgery Fellow(s) 
• Orthopaedic Residency resident of Hand service 
• Pharmacists 
• Pharmacy technicians 
• Anesthesiologists 
• Numerical Randomization generator 
• SPSS statistical software 
• Microsoft Office: Word, Excel, PowerPoint 
 
 
 
 
 
 
 


 
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R. References of relevant literature 
 
1. Tosti R, Fowler J, Dwyer J, Maltenfort M, Thoder JJ, Ilyas AM. Is Antibiotic 
Prophylaxis Necessary in Elective Soft Tissue Hand Surgery? Orthopedics. 
2012;35(6). doi:10.3928/01477447-20120525-20. 
2. Harness NG, Inacio MC, Pfeil FF, Paxton LW. Rate of Infection After Carpal 
Tunnel Release Surgery and Effect of Antibiotic Prophylaxis. J Hand Surg Am. 
2010;35(2):189-196. doi:10.1016/j.jhsa.2009.11.012. 
3. Zeng W, Paul D, Kemp T, Elfar J. Prosthetic Joint Infections in Patients 
Undergoing Carpal Tunnel Release. Journal of the American Academy of 
Orthopaedic Surgeons. Mar 2017;25(3):225-229. doi:10.5435/jaaos-d-16-00343. 
4. Burke JCAP. Maximizing Appropriate Antibiotic Prophylaxis for Surgical 
Patients: An Update from LDS Hospital, Salt Lake City. Clinical Infectious 
Diseases. 2001;33(s2). doi:10.1086/321861. 
5. LeBlanc, Martin R., Donald H. Lalonde, Achilleas Thoma, Mike Bell, Neil Wells, 
Murray Allen, Peter Chang, Daniel McKee, and Jan Lalonde. “Is Main Operating 
Room Sterility Really Necessary in Carpal Tunnel Surgery? A Multicenter 
Prospective Study of Minor Procedure Room Field Sterility Surgery.” Hand (New 
York, N.Y.) 6, no. 1 (March 2011): 60–63. https://doi.org/10.1007/s11552-010-
9301-9. 
6. CTS-6.  Diagnostic Aide for Carpal Tunnel Syndrome.  Orthoguidelines.org;  
American Academy of Orthopaedic Surgeons.  
http://www.orthoguidelines.org/ctsdiagnosis  
7. Shin, Eon K., Abdo Bachoura, Sidney M. Jacoby, Neal C. Chen, and A. Lee 
Osterman. “Treatment of Carpal Tunnel Syndrome by Members of the American 
Association for Hand Surgery.” Hand (New York, N.Y.) 7, no. 4 (December 
2012): 351–56. https://doi.org/10.1007/s11552-012-9455-8. 
8. Shapiro, S. “Microsurgical Carpal Tunnel Release.” Neurosurgery 37, no. 1 (July 
1995): 66–70. 
9. Bykowski, Michael R., Wesley N. Sivak, James Cray, Glenn Buterbaugh, Joseph 
E. Imbriglia, and W. P. Andrew Lee. “Assessing the Impact of Antibiotic 
Prophylaxis in Outpatient Elective Hand Surgery: A Single-Center, Retrospective 
Review of 8,850 Cases.” The Journal of Hand Surgery 36, no. 11 (November 
2011): 1741–47. https://doi.org/10.1016/j.jhsa.2011.08.005. 
10. Hanssen, Arlen D., Amadio Peter C., Stephen P. DeSilva, and Duane M. Ilstrup. 
“Deep Postoperative Wound Infection after Carpal Tunnel Release.” The Journal 
of Hand Surgery 14, no. 5 (September 1, 1989): 869–73. 
https://doi.org/10.1016/S0363-5023(89)80093-0. 
11. Leinberry, Charles F., Michael Rivlin, Mitchell Maltenfort, Pedro Beredjiklian, 
Jonas L. Matzon, Asif M. Ilyas, and Douglas T. Hutchinson. “Treatment of Carpal 
Tunnel Syndrome by Members of the American Society for Surgery of the Hand: 
A 25-Year Perspective.” The Journal of Hand Surgery 37, no. 10 (October 2012): 
1997–2003.e3. https://doi.org/10.1016/j.jhsa.2012.07.016. 
12. Szabo, Robert M. “Perioperative Antibiotics for Carpal Tunnel Surgery.” The 
Journal of Hand Surgery 35, no. 1 (January 1, 2010): 122–24. 
https://doi.org/10.1016/j.jhsa.2009.10.023.