ABSTRACT Gout is the most common inflammatory arthritis, affecting more than 9 million American adults, with a disease burden rising worldwide. Despite substantial clinical consequences, gout care is inconsistent, with considerable gaps in the evidence base. The primary contributor to heterogeneous gout care is a lack of agreement about the value of achieving a target serum urate (SU), due to a lack of high-level evidence. Rheumatology guidelines emphasize a treat to target serum urate (TTT-SU) approach (e.g., SU <6 mg/dL, a urate sub- saturation point); however, citing the absence of evidence, SU is not even measured during urate-lowering therapy in the vast majority of gout patients in primary care practice, where >90% of gout care occurs. We aim to generate high-level evidence to resolve the guideline conflict by mobilizing rheumatologists and primary care providers (PCPs). Furthermore, gout is a metabolic condition complicated by a high risk of myocardial infarction, diabetes, chronic kidney disease, and premature death, although it remains unknown whether gout causally leads to these outcomes. Removing monosodium urate crystal deposition by lowering SU can reduce gouty inflammation, likely by blunting the inflammasome pathway. However, it is unknown whether lowering SU results in less kidney damage, better glycemic control, or reduced cardiovascular risk. NIH funding allowed us to convene a conference in 2018 (R13AR073116) with PCPs and rheumatologists to examine the existing data, define the controversies, and elicit input on the necessary information to fill the critical evidence gap. Informed by this conference, we received funding in 2020 (AR076077) to plan a randomized controlled trial (RCT). During the past 1.5 years, we carried out key activities to gain insights from all relevant stakeholders. A modified Delphi Panel, including gout patients, nurses and physician assistants, PCPs, and rheumatologists, came to consensus regarding key protocol decisions. Mock recruitment activities allowed us to test and refine feasible procedures which will lead to successful pre-screening, screening, and patient recruitment during the proposed multi-site RCT with the following two aims. Aim 1) To conduct a RCT comparing TTASx with TTT-SU among patients with gout and hyperuricemia (HU). We have developed a trial protocol acceptable for all relevant stakeholders that will effectively answer the primary hypothesis that a TTT-SU strategy results in significantly fewer gout flares (primary outcome) over a two-year follow-up than TTASx. To ensure equipoise and generalizability, we will recruit patients from PCP practices. Aim 2) To test the effects of lowering SU on kidney function, glycemic status, and blood pressure among patients with gout enrolled in the RCT. The corresponding hypotheses are that lowering SU to a greater extent in the TTT-SU arm compared with TTASx will result in: a) slower decline in estimated glomerular filtration rate; b) lower HbA1...