Clinical trial NCT03949751: Acne crème to Reduce Propionibacterium Acnes Load in Primary Shoulder Surgery
Official title: Can Propionibacterium Acnes Load in Primary Shoulder Surgery be Reduced With Preoperative Application of a Benzoylperoxid/Miconazolnitrat crème Additional to Standard Antibiotic Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Shoulder Infections
Keywords: gram positive bacteria
Benzoylperoxid and Miconazolnitrat
Lead sponsor: Balgrist University Hospital
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 30 patients will get Acne Crème Plus (Benzoylperoxid and Miconazolnitrat) to apply until operation (on average 7 days) after receiving written consent. The application should be done daily in the evening on the planned operative side covering the skin from the nipple-areola complex laterally to the medial margin of the scapula and from a horizontal line through the nipple-areola complex cranially over the shoulder and dorsally to the spina scapulae. 30 patients will be included in the control group. Those patients will not get the local therapy in the preoperative consultation but they will need to give written consent for taking swabs for culture samples pre- and intraoperative.
Primary purpose: TREATMENT

Brief summary: 60 patients undergoing first time open shoulder surgery (Latarjet, prosthesis) will be prospectively included in this study. The investigators will do a randomized controlled trial, choosing with a single-blinded protocol 30 patients for local therapy and other 30 patients as the control group without any treatment preoperative. In the preoperative consultation 30 patients will get Acne Crème Plus (Benzoylperoxid and Miconazolnitrat) to apply until operation (on average 7 days) after receiving written consent. The application should be done daily in the evening on the planned operative side covering the skin from the nipple-areola complex laterally to the medial margin of the scapula and from a horizontal line through the nipple-areola complex cranially over the shoulder and dorsally to the spina scapulae. 30 patients will be included in the control group. Those patients will not get the local therapy in the preoperative consultation but they will need to give written consent for taking swabs for culture samples pre- and intraoperative. In the operation room there will be done from each of the 60 patients a superficial skin swab before doing disinfection, a swab of the subcutaneous layer and a swab of the deep layer (joint capsule). All the three swabs from each of the 60 patients will be sent to Unilabs, Labor für Medizinische Analytik AG, Dübendorf, Switzerland to streak on agar plates to cultivate under anaerobic conditions for 14 days. Propionibacterium acnes will be identified by use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Detailed description: According to recent studies, Propionibacterium acnes is found in 30% of patients with no preliminary shoulder operation and without obvious signs of infection. This bacterium is supposed to be the main pathogen causing shoulder infections. As it resides in the subcutaneous layer, many antiseptic and antibiotic agents that affect other layers fail to prevent infections. When administering antibiotics to reduce infections due to Propionibacterium acnes, cross-resistances to various antibiotics are created. Therefore, the investigators aim to investigate the efficacy of a local combination therapy without antibiotics (Benzoylperoxid and Miconazolnitrat) to reduce the presence of Propionibacterium acnes in patients first time undergoing open shoulder surgery. The investigators will also demonstrate the rate of positive cultures for Propionibacterium acnes in different layers regarding gender and age of patients. To best knowledge, no randomized controlled trials investigating the efficacy of Benzoylperoxid and Miconazolnitrat for reduction of Propionibacterium acnes in patients undergoing first time open shoulder surgery exist in the literature. However, in 1989 a clinical trial could demonstrate a 66% reduction of inflammatory acne lesions by applying a lotion containing Benzoylperoxid and Miconazol.

The investigators suppose that the patients with the local therapy (therapy group) show fewer positive samples than the patients of the control group as the combination of Benzoylperoxid and Miconazolnitrat (Widmer Acne Crème Plus, approval number 47033, Swissmedic) is used in the therapy of acne where Propionibacterium acnes is the major pathogen. By decreasing the presence of Propionibacterium acnes, infections and revision surgeries could be reduced as well. The investigators expect a higher rate of positive cultures from the subcutaneous layer compared to the superficial and to the deep layer. The investigators await more positive cultures in men than in women as men show a higher density of the glands in the subcutaneous layer where Propionibacterium acnes is linked to. For the same reason, the investigators suppose also a higher number of positive culture samples in younger patients (≤40 years) than in older patients (\>40 years).

60 patients undergoing first time open shoulder surgery (Latarjet, prosthesis) will be prospectively included in this study. The investigators will do a randomized controlled trial, choosing with a single-blinded protocol 30 patients for local therapy and other 30 patients as the control group without any treatment preoperative. In the preoperative consultation 30 patients will get Acne Crème Plus (Benzoylperoxid and Miconazolnitrat) to apply until operation (on average 7 days) after receiving written consent. The application should be done daily in the evening on the planned operative side covering the skin from the nipple-areola complex laterally to the medial margin of the scapula and from a horizontal line through the nipple-areola complex cranially over the shoulder and dorsally to the spina scapulae. 30 patients will be included in the control group. Those patients will not get the local therapy in the preoperative consultation but they will need to give written consent for taking swabs for culture samples pre- and intraoperative. In the operation room there will be done from each of the 60 patients a superficial skin swab before doing disinfection, a swab of the subcutaneous layer and a swab of the deep layer (joint capsule). All the three swabs from each of the 60 patients will be sent to Unilabs, Labor für Medizinische Analytik AG, Dübendorf, Switzerland to streak on agar plates to cultivate under anaerobic conditions for 14 days. Propionibacterium acnes will be identified by use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The number of positive culture samples from the therapy group will be compared with the number of positive culture samples from the control group.

Determination of Sample Size was done by performing a power analysis using www.clincalc.com, a sample size calculator placed at disposal by Sean P. Kane (clinical pharmacist, assistant professor at Rosalind Franklin University of Medicine and Science, North Chicago and advocate of evidence-based medicine). The study groups are two independent groups as they receive different treatments. The primary endpoint is dichotomous. The anticipated incidence of the therapy group is defined as 30%, the incidence of the control group is supposed to be 3-5% and the enrolment ratio is 1. The probability of a type-I-error is 0.05. With obtaining a power of 80%, between 56 and 70 participants are needed for the study according to the sample size calculator.

Recent studies could show that 30% of the patients without any obvious signs for infection and no preliminary operation have positive culture samples for Propionibacterium acnes, the investigators expect this result as well. The investigators suppose that the patients with the local therapy (therapy group) show fewer positive samples than the patients of the control group as the combination of Benzoylperoxid and Miconazolnitrat is used in the therapy of acne where Propionibacterium acnes is the major pathogen. As it is known that Propionibacterium acnes resides in the subcutaneous layer, the investigators expect a higher rate of positive cultures from the subcutaneous layer compared to the superficial and to the deep layer. The investigators expect more positive cultures in men than in women as men show a higher density of the glands in the subcutaneous layer where Propionibacterium acnes is linked to. The investigators suppose also a higher number of positive culture samples in younger patients (≤40 years) than in older patients (\>40 years).

Eligibility criteria: Inclusion Criteria:

* Patients undergoing first time open shoulder surgery (Latarjet, prosthesis)
* Male and female patients
* Age \> 18 years
* Competent German language skills
* Written informed consent as documented by signature (Appendix Informed Consent Form)

Exclusion Criteria:

* Previous enrollment into the current study,
* known or suspected non-compliance, drug or alcohol abuse,
* participation in another study with investigational drug within the 30 days preceding and during the present study,
* pregnancy or breast feeding (see chapter 3.7),
* preliminary shoulder surgeries,
* patients planned for an arthroscopic shoulder surgery,
* hypersensitivity to Benzoylperoxid or Miconazol,
* use of other acne preparations

Primary outcomes:
measure: Positive Propionibacterium acnes sample therapy group before therapy
timeFrame: 1 day
measure: Positive Propionibacterium acnes sample control group before surgery
timeFrame: 1 day
measure: Change of positive Propionibacterium acnes sample therapy group after therapy
timeFrame: Around 7 days
measure: Change of positive Propionibacterium acnes sample control group intraoperative
timeFrame: Around 7 days
Secondary outcomes:
measure: Change of positive Propionibacterium acnes in different layers
timeFrame: Around 7 days
measure: Change of positive Propionibacterium acnes gender-related
timeFrame: Around 7 days
measure: Change of positive Propionibacterium acnes age-related
timeFrame: Around 7 days
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Balgrist
Study officials:
affiliation: Balgrist University Hospital
name: Samy Bouaicha, PD Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Padegimas EM, Lawrence C, Narzikul AC, Zmistowski BM, Abboud JA, Williams GR, Namdari S. Future surgery after revision shoulder arthroplasty: the impact of unexpected positive cultures. J Shoulder Elbow Surg. 2017 Jun;26(6):975-981. doi: 10.1016/j.jse.2016.10.023. Epub 2017 Jan 10.
citation: Achermann Y, Sahin F, Schwyzer HK, Kolling C, Wust J, Vogt M. Characteristics and outcome of 16 periprosthetic shoulder joint infections. Infection. 2013 Jun;41(3):613-20. doi: 10.1007/s15010-012-0360-4. Epub 2012 Nov 3.
citation: Levy O, Iyer S, Atoun E, Peter N, Hous N, Cash D, Musa F, Narvani AA. Propionibacterium acnes: an underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg. 2013 Apr;22(4):505-11. doi: 10.1016/j.jse.2012.07.007. Epub 2012 Sep 13.
citation: Dodson CC, Craig EV, Cordasco FA, Dines DM, Dines JS, Dicarlo E, Brause BD, Warren RF. Propionibacterium acnes infection after shoulder arthroplasty: a diagnostic challenge. J Shoulder Elbow Surg. 2010 Mar;19(2):303-7. doi: 10.1016/j.jse.2009.07.065. Epub 2009 Nov 1.
citation: Phadnis J, Gordon D, Krishnan J, Bain GI. Frequent isolation of Propionibacterium acnes from the shoulder dermis despite skin preparation and prophylactic antibiotics. J Shoulder Elbow Surg. 2016 Feb;25(2):304-10. doi: 10.1016/j.jse.2015.08.002. Epub 2015 Oct 9.