CYCLIC LOCAL ANTIBIOTIC IRRIGATION TO TREAT PERIPROSTHETIC JOINT INFECTION: 24-MONTH TREATMENT OUTCOMES FROM TWO PROSPECTIVE, RANDOMIZED TRIALS

Introduction and Aim Periprosthetic joint infection (PJI) remains one of the most devastating complications following total joint arthroplasty, and a leading indication for revision surgery. As the incidence of PJI continues to rise, treatment outcomes remain constrained by sub-optimal standard-of-care treatment options. We conducted two prospective, randomized, multi-center, FDA-regulated clinical trials evaluating a novel PJI treatment* that uses cyclic, local, antibiotic irrigation to deliver high concentrations of vancomycin and tobramycin directly to the infected joint. Methods Patients with chronic hip or knee PJI were randomized to receive the CLEAR (cyclic, local, expedited, antibiotic-irrigation regimen) protocol with drug and device combination product* (CLEAR) or two-stage exchange arthroplasty (control) and followed for 24 months. CLEAR patients received 7 days of intra-articular cyclic irrigation with 80 mg tobramycin once daily, then hourly irrigation with 125 mg of vancomycin. The primary outcome was treatment success following explantation of the infected prosthesis, defined as infection control without suppressive antibiotics. Infection control included permanent prosthesis reimplantation, absence of reoperation, absence of PJI, and survival. Secondary outcomes included reimplantation rate, time to reimplantation, operative time, septic revision rate, and mortality. Results A total of 152 randomized patients underwent explantation [CLEAR: 76 patients; mean age: 67.0, 42.1% female, 89.5% White, mean BMI: 31.8, 56.6% knee; Control: 76 patients; mean age: 65.3, 32.9% female, 90.8% White, mean BMI: 34.0, 63.2% knee], of which 141 (93.0%) completed the 24-month assessment. At 24 months, 74.0% of patients (51/69) in the CLEAR group achieved treatment success compared to 51.4% in the control (37/72; significant nominal p=0.0058). Reimplantation rates were higher with the CLEAR protocol (100% vs. 87%), mean time to reimplantation was markedly shorter (7 vs. 127 days), and mean total operative time in the explant and reimplant surgeries was shorter (304 min vs 363 min). The control group experienced 83% more unplanned septic reoperations through 24 months (22 vs 12). The mortality rate at 24 months was higher in the control group (9.7% vs 7.2%). Conclusions The CLEAR protocol with the drug and device combination product* demonstrated superior outcomes at 24 months compared to two-stage exchange for chronic PJI. More patients treated using the CLEAR protocol with the drug and device combination product* received a permanent prosthesis, in a significantly shorter time, and more achieved treatment success, with shorter total operative time and fewer unplanned septic reoperations. These findings support the CLEAR protocol with the drug and device combination product* as a promising therapeutic strategy for the treatment of chronic PJI. * VT-X7 (Osteal Therapeutics)