Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures

Study Overview
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Brief Summary
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The prevention of infection is the single most important goal influencing peri-operative care of patients with open fractures. Standard practice in the management of open fractures includes sterile technique and pre-operative skin preparation with an antiseptic solution. The available solutions kill bacteria and decrease the quantity of native skin flora, thereby decreasing surgical site infection (SSI). While there is extensive guidance on specific procedures for prophylactic antibiotic use and standards for sterile technique, the evidence regarding the choice of antiseptic skin preparation solution is very limited for open fracture surgery.

Official Title
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Aqueous-PREP: A Pragmatic Randomized Trial Evaluating Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures

Conditions
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Surgical Site Infection, Unplanned Fracture-Related Reoperation, Open Appendicular Fracture

Intervention / Treatment
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* Drug: 10% povidone-iodine (1% free iodine) in purified water
* Drug: 4% chlorhexidine gluconate (CHG) in purified water


Participation Criteria
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Eligibility Criteria
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The inclusion criteria are: Patients 18 years of age or older. Open fracture of the appendicular skeleton. Received or will receive definitive fracture treatment with a surgical implant(s) (e.g., internal fixation, external fixation, joint prosthesis, etc.). Open fracture wound management that includes formal surgical debridement within 72 hours of their injury. Will have all planned fracture care surgeries performed by a participating surgeon or delegate. Informed consent obtained. Patient enrolled within 3 weeks of their fracture. The exclusion criteria are: Patients that did not or will not receive the allocated pre-operative surgical preparation solution due to a medical contraindication. Received previous surgical debridement or management of their open fracture at a non-participating hospital or clinic. Open fracture managed outside of the participating orthopaedic service (e.g., hand fracture managed by plastic surgeon). Chronic or acute infection at or near the fracture site at the time of initial fracture surgery. Burns at the fracture site. Incarceration. Expected injury survival of less than 90 days. Terminal illness with expected survival less than 90 days. Previous enrollment in a PREP-IT trial. Currently enrolled in a study that does not permit co-enrollment. Unable to obtain informed consent due to language barriers. Likely problems, in the judgment of study personnel, with maintaining follow-up with the patient. Excluded due to sampling strategy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Treatment allocation will be determined using a cluster-randomized crossover trial design. The order of treatment allocation for each orthopaedic practice will be randomly assigned using a computer generated randomization table. Each site will start with the initially allocated study solution and eventually crossover to the other solution for their second recruitment period. This process of alternating treatments will repeat approximately every 2 months as dictated by the initial randomization.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10% povidone-iodine (1% free iodine) in purified water<br>The povidone-iodine solution will contain 10% povidone-iodine (1% free iodine) in purified water as the only active ingredient. Operating room personnel will apply the solution to the operative site as the final preoperative skin antisepsis preparation immediately prior to commencing surgical fixation. They will apply the solution as per manufacturer's directions for use (e.g., technique of application, duration of application, drying time, drying techniques, replacement of draping, etc.). | Drug: 10% povidone-iodine (1% free iodine) in purified water<br>* Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all open fracture surgeries for a two-month period.<br>Drug: 4% chlorhexidine gluconate (CHG) in purified water<br>* Once the first intervention phase is completed, each site will crossover to the opposite study solution. Each site will need to develop local procedures to ensure a successful crossover. They will use the second solution for all open fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase.<br>|
| Experimental: 4% chlorhexidine gluconate (CHG) in purified water<br>The CHG solution will contain 4% CHG in purified water as the only active ingredient. Operating room personnel will apply the solution to the operative site as the final preoperative skin antisepsis preparation immediately prior to commencing surgical fixation. They will apply the solution as per manufacturer's directions (e.g., technique of application, duration of application, drying time, replacement of draping, etc.). | Drug: 10% povidone-iodine (1% free iodine) in purified water<br>* Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all open fracture surgeries for a two-month period.<br>Drug: 4% chlorhexidine gluconate (CHG) in purified water<br>* Once the first intervention phase is completed, each site will crossover to the opposite study solution. Each site will need to develop local procedures to ensure a successful crossover. They will use the second solution for all open fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Superficial Incisional Surgical Site Infection (SSI) | Guided by the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network reporting criteria (2017): Date of event for infection may occur from the date of fracture to 30 days after the definitive fracture management surgery; AND involves only skin and subcutaneous tissue of the incision; AND patient has at least one of the following: purulent drainage from the superficial incision. organisms identified from an aseptically obtained specimen from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment superficial incision that is deliberately opened by a surgeon, and culture or non-culture-based testing is not performed. AND patient has at least one of the following signs or symptoms: pain or tenderness; localized swelling; erythema; or heat. diagnosis of a superficial incisional SSI by the surgeon. | Within 30 days of the patient's last planned fracture management surgery | 
| Number of Participants With a Deep Incisional or Organ/Space Infection | Guided by CDC's National Healthcare Safety Network Surgical Site Infection reporting criteria (2017): Deep Incisional Infection: Occurs within 90 days post definitive fracture management; & involves fascial/muscle layers; & has at least one of the following: deep incision purulent drainage a deep incision that dehisces, or is opened by a surgeon, and organism is identified by microbiologic testing; or microbiologic testing is not performed & has at least one of the following: fever (> 38 °C); localized pain or tenderness other evidence of deep incision infection on anatomical exam or imaging test Organ/Space Infection: Occurs within 90 days post definitive fracture management; & involves any part of the body deeper than the fascial/muscle layers; & has at least one of the following: organ/space purulent drainage organisms in organ/space identified by microbiologic testing other evidence of organ/space infection on anatomical exam or imaging test | Within 90 days of the patient's last planned fracture management surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Unplanned Fracture-Related Reoperation | Common examples include any unplanned fracture-related surgery that is associated with an infection at the operative site or contiguous to it, a wound-healing problem, or a fracture delayed union or non-union. | Within 12 months of the patient's last planned operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgical Site Infection, Open Fracture, Povidone-iodine, Chlorhexidine gluconate, Peri-operative Preparation Solutions