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.