Losartan to Improve Outcomes after multi-ligament kNee injury (LION Trial)

Background: Multi-ligament knee injuries (MLKI) are complex injury patterns that affect two or more ligaments of the knee. Although surgical intervention can improve functional and clinical outcomes, a large percentage of patients are unable to return to preoperative activity levels. One reason for this is loss of knee range of motion (ROM), which characterizes the exaggerated pro-inflammatory environment of arthrofibrosis and is associated with future osteoarthritis risk. The purpose of this study is to assess the effectiveness of a 30-day course of losartan, a common angiotensin II antagonist, in improving surgical outcomes one year after MLKI surgery by reducing arthrofibrosis and pro-inflammatory signaling. Our hypothesis is that individuals who undergo MLKI reconstruction and take losartan will report an increased ability to return to activity, improved ROM, and decreased synovitis. Methods: This is a randomized, double-blinded, placebo-controlled clinical trial that aims to recruit 90 patients who are undergoing MLKI reconstruction. Upon enrollment, patients will be randomly assigned to a 30-day postoperative course of oral losartan or placebo on a 1:1 basis. The primary outcome will be the Cincinnati Occupational Rating Scale (CORS) Questionnaire Score which will quantify self-reported physical function. The secondary outcomes will include the time to return to active duty, work, and/or sport after surgery; International Knee Documentation Committee (IKDC) Subjective Knee Scores; Visual Analogue Scale (VAS) Pain Scores; knee ROM; quadricep strength; and ultrasound measures of persistent synovitis. Discussion: There is an unmet need for interventions to reduce inflammation and arthrofibrosis following MLKI to both rescue ROM and improve rates of return to activity. The LION Trial is a randomized, placebo-controlled clinical trial that will evaluate the efficacy of a 30-day course of losartan following MLKI reconstruction. The results of this study have the potential to redefine perioperative management and improve long-term functional outcomes for all patients undergoing ligament reconstruction with a widely available and inexpensive medication. Trial registration: Clinicaltrials.gov #NCT06933706. Registered on April 11th, 2025.