Clinical trial NCT03115177
Conditions: Osteoarthritis
Sponsor: Rush University Medical Center
Start date: 2015-11-01; Completion date: 2017-02-01
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate antibiotic treatment to target bacteria about the shoulder. This bacteria, Propionibacterium acnes, is detected in many revision shoulder surgeries and is thought to contribute to periprosthetic joint infections, pain, and failure of total shoulder arthroplasty as well as other shoulder surgeries. This study is investigating adding an FDA approved antibiotic that is commonly used for treatment of this bacteria and many common infections. The investigators will take intraoperative cultures to look for the presence or absence of specific bacteria. The investigators are conducting this trial to see if adding another antibiotic to specifically target this common bacteria found around the shoulder will be effective.

Detailed description:
Patients undergoing total and reverse shoulder arthroplasty for primary glenohumeral arthritis will be invited to participate in this study if patients meet inclusion and exclusion criteria. Patients will be randomized to receive either standard perioperative antibiotics with cefazolin or to the treatment group to receive doxycycline in addition to cefazolin. Patients will then undergo routine surgical treatment. 3 cultures from the superficial tissue, dermis, and glenohumeral joint will be taken and cultured for 14 days to detect any bacterial growth.

Arms: arm 1: All patients will receive standard perioperative antibiotics with 2g of cefazolin within 1 hour of incision. The control group will not receive any further antibiotic treatment. arm 2: All patients will receive standard perioperative antibiotics with 2g of cefazolin within 1 hour of incision. The treatment group will receive 100mg of doxycycline IV in addition to cefazolin within 1 hour of incision.
Interventions: intervention 1: Doxycycline intervention 2: Cefazolin
Intervention descriptions: intervention 1: The treatment group will receive 100mg of doxycycline IV in addition to cefazolin within 1 hour of incision for total shoulder arthroplasty. intervention 2: None

Protocol documents:
Prot_000.pdf: 
Does Pre-Operative Doxycycline Reduce Propionibacterium Acnes in Shoulder 
Arthroplasty? 
NCT03115177 
5/16/2018 
 
 


 
Study Design and Patients 
This study was reviewed and approved by the Institutional Review Board (IRB) and 
registered on clinicaltrials.gov protocol number 15052002. Patients undergoing primary 
total anatomic (TSA) or reverse shoulder arthroplasty (RTSA) were screened for 
eligibility. Inclusion criteria included patients diagnosed with primary osteoarthritis, 
rotator cuff arthropathy, or post-traumatic arthritis indicated for a total or reverse 
shoulder arthroplasty. Patients who had a recent corticosteroid injection were also 
included; this information however was not documented or recorded. Exclusion criteria 
included patients with any prior arthroscopic or open shoulder surgery to the affected side, 
patients with a known history of infection or recent antibiotic use within 90 days, and 
patients with a known allergy to doxycycline or penicillin.  
 
Randomization 
After informed consent, patients were randomized in a one to one ratio into either the 
control group or the treatment group. All patients received standard perioperative 
antibiotics with weight-based cefazolin (2g for under 120kg, 3g for over 120kg) within 1 
hour of incision and continued for 24 hours postoperatively. The control group did not 
receive any further antibiotic treatment. The treatment group received 100mg of 
doxycycline IV in addition to cefazolin prior to incision. Randomization was performed 
pre-operatively using opaque envelopes selected at the time of enrollment and consent. 
As only outcomes of the study were culture positivity from cultures obtained at the time 
of surgery, we did not include a placebo and the surgeon and patient were not blinded to 
the treatment.  


 
Surgical Procedure 
Patients underwent a standard TSA or RTSA. All patients underwent a standard skin 
preparation with both alcohol and chlorhexidine (Chloraprep (Becton, Dickinson, and 
Company, Franklin Lakes, NJ)). The patients did not have any other pre-admission skin 
cleaning or scrub. Surgical draping included the use of Ioban in all cases. The axilla is not 
routinely shaved at our institution. In the treatment group, doxycycline was infused 
starting ninety minutes prior to skin incision. This infusion was given over one hour to 
prevent thrombophlebitis as per the recommendations of our pharmacist. Once the 
doxycycline infusion was complete, the line was then flushed with normal saline, and 
cefazolin was infused over thirty minutes prior to skin incision. In the control group, the 
cefazolin was infused over thirty minutes prior to skin incision. 
 
During the procedure, aerobic and anaerobic cultures were taken. These culture included 
(1) an excisional tissue biopsy of the skin edge, (2) a tissue swab of the superficial dermal 
tissue within the incision, and (3) a tissue swab of the glenohumeral joint. The first 
culture was taken immediately after incision and was an excision of the skin edge that 
was approximately 1 cm in length and 3 mm in width from the medial edge at the middle 
of the incision. The second culture was taken immediately after incision by taking a swab 
of the superficial dermal tissue within the incision. The third culture was taken after the 
joint was entered by takedown of the subscapularis by taking a swab of the glenohumeral 
joint of the humeral head surface. Each of these cultures were incubated for fourteen days 
for both aerobic and anaerobic culture to allow for P acnes detection. We followed our 


standard surgical protocol, using a separate knife and instrumentation for superficial 
dissection and deep dissection.  
 
 

SAP_001.pdf: 
Does Pre-Operative Doxycycline Reduce Propionibacterium Acnes in Shoulder 
Arthroplasty? 
NCT03115177 
5/16/2018 
 
 


Sample size Determination: 
The primary outcome variable was culture positive results. An a priori power analysis 
was conducted, with standard deviation culled from previous studies. The mean rate of 
P.acnes culture positivity was 28% with a standard deviation of 18.8%. For an 80% 
chance of detecting a 50% difference between groups, 28 patients per group, or 56 
patients total, was needed.  
 
Statistical Analysis 
Descriptive statistics were calculated with mean and standard deviation for continuous 
variables and frequency with percentages for categorical variables. Data were found to be 
normally distributed by Kolmogorov-Smirnov testing. Groups were compared using two 
sample t-tests for continuous variables and Fisher exact tests for categorical variables. 
Significance was defined as p<0.05.