Losartan to Improve Outcomes After Multi-ligament Knee Injury

Whether the result of military training, a sports injury, or trauma, multi-ligament knee injuries (MLKIs) can be devastating events. MLKI treatment is complex and 38% of all patients report postoperative complications. Loss of knee range of motion (ROM) is the most common complication and is significantly associated with military separation. There are long-term effects of ROM loss, as the need for motion-restoring surgery after MLKI was a significant predictor of physician-diagnosed osteoarthritis within 5 years of surgery. An individual's ability to perform both activities of daily living and higher demand physical activities is thus frequently impaired both in the short and long term. Losartan, an angiotensin receptor blocker, is an FDA-approved treatment for hypertension but because of its multiple mechanisms of action, this low-cost and widely available medication could be repurposed to improve outcomes after MLKI. Objectives: The purpose of this study is to determine if a 30-day course of oral losartan will improve a person's ability to return to duty or sport within 12 months post-surgery, improve range of motion and strength, and reduce synovitis and capsular thickening after MLKI. Specific Aims and Study Design: The LION Trial is a double-blind Randomized Controlled Trial to compare the losartan versus placebo with the primary outcome variable being Cincinnati Occupational Rating Scale scores 12 months after surgery. Ninety patients enrolled and will be randomized to take either 25 mg/day of losartan or oral placebo for the first 30 days after surgery. Assessments will include patient-reported outcomes, time to return to duty/sport, knee ROM, isokinetic strength testing, and quantitative ultrasound assessments of synovitis and capsular thickening. Data will be collected at 4 time points: preoperative, after completing the 30-day course of study medication, and 6 months and 12 months after surgery. The investigators will test the following specific aims: Aim 1: Determine if a 30-day postoperative course of losartan improves the ability to return to duty or sports and patient-reported outcomes when compared to placebo following MLKI. Aim 2: Assess whether losartan results in more symmetric knee range of motion and quadriceps strength following MLKI when compared to placebo. Aim 3: Compare ultrasound measures of capsular thickening and synovitis between groups treated with losartan versus placebo following surgical treatment of MLKI.