Randomized Trial of Hibiclens vs Benzoyl Peroxide Soap for Surgical Preparation
Phase: PHASE4
Conditions: Propionibacterium Acnes
Sponsor: University of Washington

Randomized Trial of Hibiclens vs Benzoyl Peroxide Soap for Surgical Preparation 
NCT04021524 
Study Protocol and SAP 
5/8/2020 
 
 

Study Protocol 
Adult male patients planning to undergo shoulder arthroplasty were assessed for 
eligibility by a research coordinator at their pre-operative appointment in the clinic. The 
study was confined to male patients because of their higher risk of Cutibacterium 
periprosthetic infections. Exclusion criteria were as follows: (1) self-reported skin 
sensitivity, (2) reported sensitivity or allergy to either chlorhexidine or benzoyl peroxide, 
(3) use of antibiotics within three months of surgical date, (4) use of medication for acne 
within three months of surgical date, and (5) lack of fluency in the English language. 
Patient age, sex, American Society of Anesthesiologist (ASA) classification, body mass 
index (BMI), and history of previous surgery on ipsilateral shoulder were recorded.  
The patients were randomized by a research coordinator using simple randomization 
implemented through REDCap. The first group received a bottle of 4% chlorhexidine 
gluconate solution (CHG group). The second group received a bar of 10% benzoyl 
peroxide soap (BPO group). Both the chlorhexidine solution and benzoyl peroxide soap 
were stocked in the clinic so that all patients in each group received the same 
preparation. Both groups were instructed to apply the wash or soap to the surgical 
shoulder the night prior and the morning of surgery and to scrub for at least 60 seconds 
with the wash. The treating surgeon and all care providers were blinded to treatment 
group throughout the patient’s care.  
In the operating room, the unprepared, unshaved skin surface was sampled with a swab 
(Eswab™, #480C, Copan Diagnostics, Inc., Murrieta, CA) in the area of the planned 
incision. Four passes with the swab were taken by a surgical assistant wearing sterile 
gloves, turning the swab 90 degrees for each pass. The skin was then prepared with 
dual application of 2% CHG in 70% isopropyl alcohol and administration of intravenous 
antibiotics. Immediately after skin incision, swabs of the dermal wound edge were 
obtained in a similar fashion to the skin surface.  
All specimens were processed by the laboratory in a Class 2 laminar flow biological 
safety cabinet. Specimens were inoculated onto the following microbiological media: 
blood agar (trypticase soy agar with 5% sheep blood), chocolate agar, Brucella agar 
(with blood, hemin, and vitamin K), and brainheart infusion broth. All media, with the 
exception of the Brucella agar, were incubated at 37 °C with 5% CO2 for 21 days. 
Brucella agar plates were incubated anaerobically at 37 °C for 21 days. Plates were 
sealed in a manner that allows sterile aeration without desiccation. Media were 
examined daily for growth visually but were only opened if growth was noted.  
The cultures results were reported in a semiquantitative manner as the Specimen 
Cutibacterium Value (SpCuV) across a range of 0 (no growth) to 4 (4+ positive growth 
on agar plates). 
 
 

SAP 
An a priori sample size calculation was performed using previous data regarding growth 
of Cutibacterium from the skin of shoulder arthroplasty patients. Based on pilot data 
combined with previous published data, we estimated the incidence of positive 
Cutibacterium cultures on the skin surface of male patients to be 77%. We determined 
the sample size of 50 was necessary to detect a reduction of 50% between the two 
groups with 1:1 allocation ratio, a power of 0.80, and an alpha of 0.05. Given that the 
intervention and outcome were only separated by 1 day, we anticipated a 0% dropout 
rate. Baseline demographics were compared between groups using a t test for 
continuous variables and a chi-square test for categorical variables. The two groups 
were compared with regards to the percent positivity of the skin surface and incised 
dermal edge as well as the bacterial load at each site using a chi-square test.