# Treat-to-Target Serum Urate versus Treat-to-Avoid Symptoms in Gout: A Randomized Controlled Trial (TRUST)

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $1,937,050

## Abstract

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...

## Key facts

- **NIH application ID:** 10917026
- **Project number:** 5U01AR080985-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** MICHAEL J BARRY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,937,050
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917026

## Citation

> US National Institutes of Health, RePORTER application 10917026, Treat-to-Target Serum Urate versus Treat-to-Avoid Symptoms in Gout: A Randomized Controlled Trial (TRUST) (5U01AR080985-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10917026. Licensed CC0.

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