Clinical trial NCT05701475: Cutibacterium Acnes: Triple Prevention in Shoulder Operations
Official title: Triple Prevention Against Cutibacterium Acnes Using Benzoyl Peroxide Preparation in Addition to Pre-operative Cutaneous and Subcutaneous Iodine in Shoulder Surgery; a Single-blinded, Randomized, Controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-Operative Wound Infection
Surgical Site Infection
Keywords: Cutibacterium Acnes
Prevention
Benzoyl peroxide
Subcutaneous disinfection
Surgical site infection
Pre-operative disinfection
Lead sponsor: Clinique Générale dAnnecy
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Annecy Genevois
First posted: 2023-01-27
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled trial
Primary purpose: PREVENTION

Brief summary: Patients planned for shoulder surgery will be identified and contacted for participation. After informed consent is provided, patients will be randomised into one of three groups: pre-operative cutaneous disinfection with iodine (control group), pre-operative cutaneous and subcutaneous disinfection with iodine (double prevention), and pre-operative cutaneous and subcutaneous disinfection with iodine combined with a skin preparation protocol with benzoyl peroxide gel in the days prior to surgery (triple prevention). Bacterial cultures will be collected during surgery of the surgical field and tissue layers. Culture positivity for Cutibacterium Acnes will be compared between the groups as a primary outcome.

Detailed description: Eligible patients will be contacted for participation (see Eligibility Criteria). If subjects meet the inclusion criteria, patients will receive information regarding the study outline, associated risks, and subject rights. Informed consent must be freely given, specific, unambiguous, and may be withdrawn at any time. Subjects must be legally capable of providing consent. Consent will be and recorded in writing and stored for the duration of the study. The target for inclusion was set at 52 patients in each group, of each group 26 will be arthroscopic and 26 open surgery.

Patients will be divided into three groups of equal size:

* Triple-prevention: Benzoyl peroxide at home, subcutaneous iodine, and cutaneous iodine.
* Double-prevention: Cutaneous and subcutaneous iodine.
* Single-prevention (control group): cutaneous iodine.

Simple block randomisation will be used to prevent chronological bias and ensure equal group size. Treatments will be allocated with a 1:1:1 ratio using a block size of 12. Randomisation will be stratified by open or arthroscopic surgery to ensure an equal number in all three groups (3x2x26 patients) Random treatment allocation numbers will be generated and blinded, to be revealed after inclusion.

Benzoyl peroxide:

Patients will be instructed to apply and rub in a 5-cm strip of 5% benzoyl peroxide gel to the shoulder on dry skin in the morning and evening 2 days prior to surgery, 1 day before surgery, and a fifth time in the morning on the day of surgery.

Cutaneous iodine:

Standard pre-operative preparation including cutaneous disinfection with alcoholic iodine, sterile drapes.

Subcutaneous iodine:

Open surgery: after incision down to the fascia of the muscle layer, preparation of the whole subcutaneous layer with povidone-iodine solution will be performed and left acting during 60 seconds before full aspiration and lavage in order to not have swabs drained in povidone-iode (as it could continue to act as antiseptic during culture).

For arthroscopic procedures the disinfection and swab collection protocol will be performed when creating the first portal.

Bacterial culture swabs (n=9) will be taken during surgery from the patients' skin (before disinfection with iodine), subcutaneous tissue (after disinfection if randomised for subcutaneous disinfection), muscular layer, intra-articular/layer of the intervention (for example in case of clavicle surgery from the clavicle), surgeon's glove, outside scalpel, inside scalpel, and the retractors. For the swabs in the operative field, the applicable field is to be swabbed fully for 3 seconds. Each surgeon will follow the clear swab instructions from the microbiologist in order to obtain reliable cultures. Cultures will be analysed by the hospital's medical microbiological laboratory following standard protocol including a standard incubation time of 14 days. Treatment arm will be blinded for the laboratory employees.

Culture positivity between the groups will be analysed using chi-square tests for each culture location. In addition, a two-way ANOVA test will be performed to assess total number of positive cultures per patient. Furthermore, logistic regression models will be used to adjust for several potential confounding factors depending on the number of positive tests in the sample.

Eligibility criteria: Inclusion Criteria:

* Indication for all types of surgery at the shoulder joint, acromioclavicular joint, or clavicle, including arthroscopic and open surgery.

Exclusion Criteria:

* Previous shoulder surgery;
* History of shoulder infection;
* Antibiotic treatment in the last 6 weeks;
* Allergy or hypersensitivity to one of the disinfecting agents;
* Patients with laboratory values consistent with a current infection (C-reactive protein, erythrocyte sedimentation rate, leukocyte count).

Primary outcomes:
measure: Cutibacterium Acnes positivity
timeFrame: 14 days
Secondary outcomes:
measure: Culture positivity with other bacteria
timeFrame: 14 days
measure: Adherence to pre-operative protocol
timeFrame: 1 day
Other outcomes:
measure: Adverse reaction to Benzoyl Peroxide
timeFrame: 1 day
Locations:
city: Annecy
country: France
facility: Clinique Générale d'Annecy
Study officials:
affiliation: Clinique Générale d'Annecy
name: Geert A Buijze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moore NF, Batten TJ, Hutton CE, White WJ, Smith CD. The management of the shoulder skin microbiome (Cutibacterium acnes) in the context of shoulder surgery: a review of the current literature. Shoulder Elbow. 2021 Oct;13(6):592-599. doi: 10.1177/1758573220945226. Epub 2020 Jul 27.
citation: Moor BK, Leger B, Steffen V, Troillet N, Emonet S, Gallusser N. Subcutaneous tissue disinfection significantly reduces Cutibacterium acnes burden in primary open shoulder surgery. J Shoulder Elbow Surg. 2021 Jul;30(7):1537-1543. doi: 10.1016/j.jse.2020.11.018. Epub 2021 Jan 6.
citation: Kaveeshwar S, Duvall G, Jones DL, O'Hara NN, Klein A, Diedrich AM, Kolakowski L, Lai JK, Hasan SA, Henn RF 3rd, Gilotra MN. Risk factors for increased shoulder Cutibacterium acnes burden. JSES Int. 2020 Jun 3;4(3):464-469. doi: 10.1016/j.jseint.2020.04.020. eCollection 2020 Sep.
citation: Hudek R, Brobeil A, Bruggemann H, Sommer F, Gattenlohner S, Gohlke F. Cutibacterium acnes is an intracellular and intra-articular commensal of the human shoulder joint. J Shoulder Elbow Surg. 2021 Jan;30(1):16-26. doi: 10.1016/j.jse.2020.04.020. Epub 2020 Jun 9.
citation: Lavergne V, Malo M, Gaudelli C, Laprade M, Leduc S, Laflamme P, Rouleau DM. Clinical impact of positive Propionibacterium acnes cultures in orthopedic surgery. Orthop Traumatol Surg Res. 2017 Apr;103(2):307-314. doi: 10.1016/j.otsr.2016.12.005. Epub 2017 Jan 5.
citation: Chalmers PN, Beck L, Stertz I, Tashjian RZ. Hydrogen peroxide skin preparation reduces Cutibacterium acnes in shoulder arthroplasty: a prospective, blinded, controlled trial. J Shoulder Elbow Surg. 2019 Aug;28(8):1554-1561. doi: 10.1016/j.jse.2019.03.038. Epub 2019 Jun 20.
citation: Singh AM, Sethi PM, Romeo AA, Anakwenze OA, Abboud JA, Namdari S. Strategies to decolonize the shoulder of Cutibacterium acnes: a review of the literature. J Shoulder Elbow Surg. 2020 Apr;29(4):660-666. doi: 10.1016/j.jse.2019.11.037.
citation: Dizay HH, Lau DG, Nottage WM. Benzoyl peroxide and clindamycin topical skin preparation decreases Propionibacterium acnes colonization in shoulder arthroscopy. J Shoulder Elbow Surg. 2017 Jul;26(7):1190-1195. doi: 10.1016/j.jse.2017.03.003. Epub 2017 May 4.
citation: Kolakowski L, Lai JK, Duvall GT, Jauregui JJ, Dubina AG, Jones DL, Williams KM, Hasan SA, Henn RF 3rd, Gilotra MN. Neer Award 2018: Benzoyl peroxide effectively decreases preoperative Cutibacterium acnes shoulder burden: a prospective randomized controlled trial. J Shoulder Elbow Surg. 2018 Sep;27(9):1539-1544. doi: 10.1016/j.jse.2018.06.012. Epub 2018 Jul 24.
citation: Sabetta JR, Rana VP, Vadasdi KB, Greene RT, Cunningham JG, Miller SR, Sethi PM. Efficacy of topical benzoyl peroxide on the reduction of Propionibacterium acnes during shoulder surgery. J Shoulder Elbow Surg. 2015 Jul;24(7):995-1004. doi: 10.1016/j.jse.2015.04.003.
citation: Scheer VM, Bergman Jungestrom M, Lerm M, Serrander L, Kalen A. Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes: a randomized study. J Shoulder Elbow Surg. 2018 Jun;27(6):957-961. doi: 10.1016/j.jse.2018.02.038. Epub 2018 Mar 30.
citation: van Diek FM, Pruijn N, Spijkers KM, Mulder B, Kosse NM, Dorrestijn O. The presence of Cutibacterium acnes on the skin of the shoulder after the use of benzoyl peroxide: a placebo-controlled, double-blinded, randomized trial. J Shoulder Elbow Surg. 2020 Apr;29(4):768-774. doi: 10.1016/j.jse.2019.11.027.
citation: Scheer VM, Jungestrom MB, Serrander L, Kalen A, Scheer JH. Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure. J Shoulder Elbow Surg. 2021 Jun;30(6):1316-1323. doi: 10.1016/j.jse.2020.12.019. Epub 2021 Feb 3.
citation: Hsu JE, Whitson AJ, Woodhead BM, Napierala MA, Gong D, Matsen FA 3rd. Randomized controlled trial of chlorhexidine wash versus benzoyl peroxide soap for home surgical preparation: neither is effective in removing Cutibacterium from the skin of shoulder arthroplasty patients. Int Orthop. 2020 Jul;44(7):1325-1329. doi: 10.1007/s00264-020-04594-x. Epub 2020 May 8.
citation: Green N, Jordan RW, Maclean S, D'Alessandro P, MacDonald PB, Malik SS. Preoperative topical benzoyl peroxide treatment is effective in reducing Cutibacterium acnes in shoulder surgery: a systematic review. J Shoulder Elbow Surg. 2023 Jan;32(1):213-222. doi: 10.1016/j.jse.2022.07.019. Epub 2022 Sep 5.
citation: Stull JD, Nicholson TA, Davis DE, Namdari S. Addition of 3% hydrogen peroxide to standard skin preparation reduces Cutibacterium acnes-positive culture rate in shoulder surgery: a prospective randomized controlled trial. J Shoulder Elbow Surg. 2020 Feb;29(2):212-216. doi: 10.1016/j.jse.2019.09.038. Epub 2019 Dec 13.
citation: Rao AJ, Chalmers PN, Cvetanovich GL, O'Brien MC, Newgren JM, Cole BJ, Verma NN, Nicholson GP, Romeo AA. Preoperative Doxycycline Does Not Reduce Propionibacterium acnes in Shoulder Arthroplasty. J Bone Joint Surg Am. 2018 Jun 6;100(11):958-964. doi: 10.2106/JBJS.17.00584.
citation: Namdari S, Nicholson T, Parvizi J, Ramsey M. Preoperative doxycycline does not decolonize Propionibacterium acnes from the skin of the shoulder: a randomized controlled trial. J Shoulder Elbow Surg. 2017 Sep;26(9):1495-1499. doi: 10.1016/j.jse.2017.06.039. Epub 2017 Jul 19.
citation: Matsen FA, Whitson AJ, Hsu JE. While home chlorhexidine washes prior to shoulder surgery lower skin loads of most bacteria, they are not effective against Cutibacterium (Propionibacterium). Int Orthop. 2020 Mar;44(3):531-534. doi: 10.1007/s00264-019-04477-w. Epub 2020 Jan 14.
citation: MacLean SBM, Phadnis J, Ling CM, Bain GI. Application of dermal chlorhexidine antisepsis is ineffective at reducing Proprionibacterium acnes colonization in shoulder surgery. Shoulder Elbow. 2019 Apr;11(2):98-105. doi: 10.1177/1758573218755570. Epub 2018 Jan 30.
citation: Duvall G, Kaveeshwar S, Sood A, Klein A, Williams K, Kolakowski L, Lai J, Enobun B, Hasan SA, Henn RF 3rd, Gilotra MN. Benzoyl peroxide use transiently decreases Cutibacterium acnes load on the shoulder. J Shoulder Elbow Surg. 2020 Apr;29(4):794-798. doi: 10.1016/j.jse.2019.06.026. Epub 2019 Oct 31.