Trial Comparing Three Single Dose Injections for Knee Osteoarthritis

This study is a 3-arm, double-blind, randomized trial comparing the clinical outcomes of Zilretta, Synvisc One, and Monovisc for knee OA.

Inclusion Criteria: * Age 25-85 years * BMI \< 40 * Diagnosis of unilateral knee OA * Radiographic evidence of OA of the target knee (Kellgren-Lawrence grades 2-4) * Continued OA pain in the target knee despite at least 6 weeks of: physical therapy and at least one of the following: activity modification (such as reducing impact on the knee), weight loss, and a 2 week trial of NSAID / acetaminophen. * Knee Osteoarthritis Outcomes Score (KOOS)-Pain subscale 20-65 * Working knowledge of English language (to be able to complete all outcome scores) * Ability to attend all follow-up appointments Exclusion Criteria: * 3+ effusion of the target knee (stroke test grading system) * Prior injection therapy: * Steroid injection in target knee in the last 3 months * Viscosupplementation in target knee in the last 6 months * PRP in the target knee in the last 6 months * Cellular treatments in index knee (bone marrow, amniotic suspensions etc) 1 year * Participation in any experimental device or drug study within 1 year before screening visit * Oral or IM steroids in the last 3 months (Inhaled steroids used in the treatment of asthma/allergies are permitted) * Medical condition that may impact outcomes of procedure including: * Systemic inflammatory disorders that impact the joints like rheumatoid arthritis, lupus, etc * Undergoing current cancer treatment (other than non-melanoma skin malignancies) * Taking immunosuppressants * Previous cartilage repair procedure on the injured cartilage surface (ie, OATS, ACI, MFX) in the last 5 years * Previous surgery at the target knee within the past 1 year * Any degree of cognitive impairment * Symptomatic OA of any other joint in the lower limbs * Pregnancy, lactating, or intent to become pregnant during treatment period (Female participants will be asked if they are pregnant, lactating, or intend to become pregnant during treatment) * Gout, Pseudogout (including radiographic evidence of chondrocalcinosis) * History of infection or current infection at the affected joint * Smoking (Former smokers\< 1 year from quit date)