PROSPECTIVE RANDOMIZED EVALUATION OF EMERGING NOVEL TREATMENTS FOR INFECTION PROPHYLAXIS IN TOTAL JOINT REPLACEMENT (PREVENT-IT): A PILOT STUDY

Osteoarthritis (OA) is the most common cause of disability in older adults worldwide. Total Joint Replacement (TJR) is the definitive treatment for OA and can drastically improve functionality, decrease pain, and improve quality of life. Despite its success, there is a small but serious risk of infection following TJR. Periprosthetic Joint Infection (PJI) in particular is a devastating and costly complication, placing its prevention atop the list of priorities among both orthopaedic surgeons and the infectious disease community. Several different interventions aimed at reducing rates of PJI have been proposed and investigated; however, none have yet demonstrated definitive efficacy. The purpose of this pilot study was to determine the feasibility of a definitive randomized controlled trial (RCT) comparing the use of irrigation fluids and topical antibiotics to reduce the risk of reoperation due to infection. This pilot study was a 3x2 factorial RCT across six centers. Participants having primary or aseptic revision hip or knee replacement were randomized to one of six possible groups: 1) 0.35% povidone-iodine lavage; 2) 0.35% povidone-iodine lavage and 2 grams of local vancomycin; 3) 0.05% chlorhexidine gluconate lavage; 4) 0.05% chlorhexidine gluconate lavage and 2 grams of local vancomycin; 5) normal saline lavage; 6) normal saline lavage and 2 grams of local vancomycin in a 1:1:1:1:1:1 ratio. Participant follow-up is six weeks, six months and one year post TJR. A traffic light approach was used to interpret the main objectives, where “green” indicates move forward with the definitive trial with no modifications, “yellow” indicates proceed with some modifications, and “red” indicates that the definitive trial is not feasible. A total of 500 participants were recruited at six different sites over a recruitment period of nine months. There were 56% females and 44% males. The mean age was 67 (standard deviation [SD] 9.98). There were 261 (52%) knees and 236 (47%) hips included. A total of 480 (96%) of procedures were primary and 17 (3%) were aseptic revisions. The overall compliance to the protocol is 94% with 15/500 (3%) of errors due to the use of additional antiseptic irrigation solutions during surgery, 3/500 (0.6%) randomization errors, 2/500 (0.4%) incorrectly enrolled and 8/500 (1.6%) those who did not receive the study intervention. There are five periprosthetic joint infections requiring reoperation and five instances of post wound drainage with one requiring reoperation. We will proceed with the definitive RCT, as the traffic light approach indicates that both recruitment at multiple sites and the administration of the study treatments is feasible. To maintain the 3x2 factorial design of the pilot study we will simplify both the frequency of follow-up and the amount of data collected in the definitive RCT.