Evaluation of Povidone, Chlorhexidine, and Vancomycin for Infection Prophylaxis in Primary or Aseptic Revision Total Joint Replacement

The primary objective of this study is to evaluate the efficacy of different irrigation solutions and local **vancomycin** in reducing the risk of reoperation due to infection within 12 months following primary or aseptic revision total joint replacement (TJR) of the hip or knee. Specifically, the study aims to determine if a 0.35% povidone-iodine (PI) irrigation solution, a 0.05% chlorhexidine irrigation solution, or the use of local vancomycin compared to their respective controls (normal saline irrigation solution or no local vancomycin) can significantly lower the incidence of infections necessitating reoperation. This is clinically relevant as it addresses the prevention of postoperative infections, a significant complication in TJR surgeries, which can lead to increased morbidity and healthcare costs.

Secondary objectives include: - Assessing the impact of a 0.35% PI irrigation solution compared to a normal saline irrigation solution on the number of non-operative surgical site infections requiring antibiotics. - Evaluating the effect of a 0.05% chlorhexidine irrigation solution compared to a normal saline irrigation solution on the number of non-operative surgical site infections requiring antibiotics. - Determining whether patients who receive local vancomycin have a lower rate of infection requiring reoperation compared to those who do not receive local vancomycin.

The clinical trial involves a total of **20,706 participants**, comprising both male and female subjects. The study population includes **adult patients** aged 18 years and older who are undergoing primary or aseptic revision total joint replacement (**TJR**) surgery. Participants were selected based on their eligibility to undergo such surgical procedures, with no vulnerable populations included in the trial. The general health status of the participants is not specified, but they are expected to be suitable candidates for TJR surgery. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. The trial does not specify any additional key inclusion or exclusion criteria beyond the age and surgical procedure requirements.

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the efficacy of novel treatments for infection prophylaxis in total joint replacement (TJR) surgeries. The trial aims to assess whether a 0.35% povidone-iodine (PI) irrigation solution, a 0.05% **chlorhexidine** irrigation solution, or local **vancomycin** application can reduce the risk of reoperation due to infection within 12 months post-surgery. The study will involve adult patients undergoing primary or aseptic revision TJR, with a planned recruitment start date in September 2024 and an estimated completion date in September 2027.

Participants will be involved in the study for a maximum of 12 months, with the trial duration encompassing the initial surgery and subsequent follow-up visits. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age (18 years or older) and the type of surgery (primary or aseptic revision TJR). Following the screening, participants will undergo the surgical procedure with the assigned treatment. Post-operative follow-up visits will be scheduled to monitor for any signs of infection and assess the need for reoperation. The end-of-study visit will occur at the 12-month mark to evaluate the primary endpoint, which is the incidence of infection requiring reoperation.

Participants may be withdrawn from the study if they experience adverse events that necessitate discontinuation of the treatment, if they withdraw consent, or if they fail to comply with the study protocol. The trial is categorized as a low-intervention study, meeting the criteria outlined in RD 1090/2015, and is conducted in accordance with ethical standards and regulatory requirements. The study's primary outcome is to determine the effectiveness of the interventions in reducing infection-related reoperations, thereby potentially improving patient outcomes in TJR surgeries.

The clinical trial involves the use of several experimental medications, each with specific characteristics and administration protocols. **Vancomycin** is utilized in this study as a chemical active substance. It is administered in a pharmaceutical form identified as PHF00230MIG, with a maximum daily and total dose of 2 grams. The route of administration is cutaneous, and the treatment period is limited to one day. Vancomycin is employed to assess its efficacy in reducing the risk of reoperation due to infection within 12 months of primary or aseptic revision hip or knee total joint replacement (TJR).

Another experimental treatment in the trial is a combination of **benzalkonium chloride**, **chlorhexidine gluconate**, and **benzyl alcohol**. This mixture is presented in a pharmaceutical form labeled as PHF00024MIG. The maximum daily and total dose is 0.05% weight/volume, administered cutaneously. The treatment duration is also restricted to one day. This combination is evaluated for its potential to decrease the risk of reoperation due to infection within the specified timeframe following TJR.

**Povidone** is included as an antiseptic agent in the trial. It is provided as a cutaneous solution with a maximum daily and total dose of 0.35% percent. The administration is cutaneous, and the treatment period is one day. Povidone's role in the study is to compare its effectiveness against a normal saline irrigation solution in reducing infection-related reoperations within 12 months post-TJR.

The trial also incorporates a non-experimental treatment, a normal saline irrigation solution, which serves as a comparator. This solution is classified under the ATC code B05XX, indicating its use as an intravenous solution additive. The maximum daily and total dose is 0.9% weight/volume, administered cutaneously, with a treatment period of one day. The saline solution is used as a standard-of-care therapy to evaluate the relative efficacy of the experimental treatments in infection prophylaxis during TJR.

Efficacy in the clinical trial titled "Prospective Randomized Evaluation of Emerging Novel Treatments for Infection prophylaxis in Total Joint Replacement (PREVENT-iT)" will be assessed by evaluating the primary endpoint, which is the occurrence of infection requiring reoperation within 12 months following total joint replacement (TJR). The trial aims to determine the effectiveness of different irrigation solutions and the use of local **vancomycin** in reducing the risk of reoperation due to infection. Specifically, the trial will compare a 0.35% povidone-iodine (PI) irrigation solution and a 0.05% chlorhexidine irrigation solution against a normal saline irrigation solution, as well as the use of local vancomycin versus no local vancomycin.

The primary endpoint will be measured by tracking the incidence of infections that necessitate reoperation within the specified 12-month period post-surgery. Data collection will occur at various time points throughout the trial, with a focus on the 12-month post-operative period to capture any reoperations due to infection. The analysis will involve comparing the rates of infection-related reoperations between the different treatment groups to determine the relative efficacy of each intervention. The trial is designed as a low-intervention study, adhering to the criteria outlined in RD 1090/2015, and is expected to conclude by September 15, 2027, with recruitment starting on September 16, 2024.