Evaluation of Vancomycin, Tobramycin, and Saline in Antibiotic-Impregnated Bone Grafts for Reducing Prosthetic Joint Infection Post-Hip Arthroplasty

The primary objective of the ABOGRAFT trial is to investigate whether **antibiotic impregnated bone graft** (AIBG) decreases the risk of infection two years after hip arthroplasty, compared to controls treated with placebo impregnated bone graft. This is clinically relevant as reducing the incidence of **prosthetic joint infection** can significantly improve patient outcomes and reduce the need for further surgical interventions.

Secondary objectives include:

• Investigating differences between the two experimental groups in time and reason for reoperation for any reason within two and five years.
• Investigating differences between the two experimental groups in time and reason for implant revision due to any reason within two and five years.
• Investigating differences between the two experimental groups in the type of microbe and antibiotic resistance pattern for cases complicated with postoperative infection.
• Evaluating the safety of using AIBG as infection prophylaxis in hip arthroplasty.

The clinical trial focuses on individuals diagnosed with **Prosthetic Joint Infection** and aims to assess the efficacy of antibiotic impregnated bone grafts in reducing infection risk post-hip arthroplasty. The study population includes both male and female participants aged 18 years and older, with no specific vulnerable populations targeted. Participants are required to have undergone hip arthroplasty necessitating a bone graft and must be willing to provide informed consent. Women of childbearing potential are required to have a negative pregnancy test prior to reoperation. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is representative of the general demographic undergoing hip arthroplasty, without any significant exclusion based on lifestyle habits.

The clinical trial is designed to evaluate the efficacy of **antibiotic impregnated bone graft** (AIBG) in reducing the risk of **prosthetic joint infection** following hip arthroplasty. This is a randomized, double-blind, controlled trial with a phase 4 designation, involving a narrow selection of 850 participants. The trial aims to compare the outcomes of patients receiving AIBG against those treated with a placebo-impregnated bone graft. The primary endpoint is the incidence of reoperation due to infection or diagnosed prosthetic joint infection with bacteria sensitive to either **vancomycin** or **tobramycin** within two years post-surgery. Secondary endpoints include the time and cause for reoperation or implant revision within two and five years, the type of microbe and antibiotic resistance pattern in cases of postoperative infection, and differences in adverse events and revision rates due to aseptic loosening between the two groups.

The trial is expected to run from March 18, 2022, to April 1, 2031. Participants will be involved for a maximum treatment period of one year. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age (≥18 years), the requirement for hip arthroplasty with bone graft, and informed consent. Women of childbearing potential must have a negative pregnancy test prior to reoperation. Follow-up visits will be scheduled to monitor the participants' health status and any adverse events. The end-of-study visit will assess the primary and secondary endpoints. Participants may be terminated early from the study if they experience significant adverse events or if they withdraw consent. The trial's methodology ensures rigorous data collection and analysis to determine the safety and effectiveness of the treatment under investigation.

The clinical trial involves the administration of three distinct treatments, each with specific pharmaceutical characteristics and administration protocols. The first treatment is **saline**, which is utilized as a **solution for injection**. This treatment is administered intraarticularly, with a maximum daily dose of 8 ml. The saline solution serves as a placebo in the study, providing a control for comparison against the experimental treatments. The administration is conducted once daily for a maximum treatment period of one day, ensuring participant compliance through direct observation and documentation of each administration.

The second treatment involves **Vancomycin MIP 1 000 mg**, presented as a **solution for infusion**. This antibiotic is administered intraarticularly, with a maximum daily dose of 1000 mg. The treatment is designed to evaluate the efficacy of vancomycin in reducing infection rates post-hip arthroplasty. The administration is performed once daily, with a maximum treatment period of one day. Compliance is monitored through the recording of infusion times and dosages, ensuring adherence to the prescribed regimen.

The third treatment is **Nebcina 80 mg/ml**, a **solution for injection** containing the active substance **tobramycin**. This antibiotic is also administered intraarticularly, with a maximum daily dose of 640 mg. The treatment aims to assess the effectiveness of tobramycin in preventing infections following hip replacement surgery. Similar to the other treatments, it is administered once daily for a maximum of one day. Participant compliance is ensured through meticulous documentation of each injection, including the time and dosage administered.

Efficacy in the clinical trial titled "Antibiotic Impregnated Bone Graft to reduce infection in hip replacement - the ABOGRAFT trial" will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the occurrence of reoperation due to infection or diagnosed **prosthetic joint infection (PJI)** with bacteria sensitive to either vancomycin or tobramycin in the same hip joint within two years post-arthroplasty. This endpoint will provide a direct measure of the intervention's effectiveness in reducing infection rates.

Secondary endpoints include the time and cause for reoperation for any reason within 2 and 5 years, the time and cause for implant revision due to any reason within the same periods, and the type of microbe and antibiotic resistance pattern in cases complicated by postoperative infection. Additionally, differences between the two experimental groups will be evaluated regarding the frequencies of adverse events and the rates of revision due to aseptic loosening. These secondary endpoints will offer a broader understanding of the intervention's impact on patient outcomes and safety.