SAVE-Care (Sodium Glucose Cotransporter-2 Inhibitors [SGLT2i] As Novel Gout Care) Trial (SAVE-Care)

SAVE-Care (SGLT2i As Novel Gout Care) Trial

SAVE-Care (Sodium Glucose Cotransporter-2 inhibitors [SGLT2i] As Novel Gout Care) Trial is a double-blind randomized placebo-controlled trial (RCT) designed to assess the effect of empagliflozin on serum urate [SU] levels of gout patients, as well as levels of highly-sensitivity C-reactive protein [hsCRP] and interleukin 6 [IL-6], and estimate gout flares over 3 months, in order to develop a full-scale RCT of clinical endpoints to directly inform gout care guidelines.

Study Overview

• Status: Recruiting
• Conditions: Gout and Hyperuricemia
• Intervention / Treatment: Drug: Empagliflozin 10 mg; Drug: Placebo

Detailed Description

With the compelling premise as above, prospective gout-patient-specific RCTs for key gout disease endpoints are needed to provide high-level evidence needed to impact practice change with a great likelihood to revolutionize gout care as SGLT2i did in cardiology, diabetology, and nephrology. To that end, the investigators propose to conduct the first RCT of SGLT2i specifically among gout patients with hyperuricemia (SAVE-Care [SGLT2i As Novel Gout Care] Trial) for the endpoint of serum urate, the central outcome in clinical care, trials, and FDA approvals, as discussed above. Specifically, the investigators will conduct a double-blind RCT of 60 gout patients, with 2 parallel arms of empagliflozin 10mg daily vs. placebo in a 2:1 ratio over 12 weeks.

The SAVE-Care trial will fill an important evidence gap by determining the magnitude of SU reduction specifically in patients with well-characterized gout, and with hyperuricemia and recent flares, for whom gout treatment would be indicated. If SU reduction is substantial (e.g. >~1.5mg/dL) as hypothesized in Aim 1, SGLT2i will be considered a useful urate-lowering gout therapy given their proven cardiovascular [CV]-kidney-metabolic benefits, particularly for typical cases managed by primary care or those with indicated CV-kidney metabolic comorbidities. However, if the urate-lowering capacity among gout patients is relatively small, SGLT2i's clinical utility for SU control purpose (vs flare control alone) will be considered limited. To that end, SU outcomes data generated by the SAVE-Care trial in relevant gout patients will be directly applicable to clinical gout care.

The SAVE-Care trial will also provide first prospective RCT outcomes data on two relevant inflammatory markers (i.e., hs-CRP and IL-6) among gout patients to assess the anti-inflammatory potentials of SGLT2i relevant to gout. Furthermore, SAVE-Care trial will generate estimates for gout flare risks and rates in the empagliflozin and in the placebo group over 12 weeks, which will serve as important preliminary data to developing a future full-scale RCT for clinical endpoints. All in all, with the overarching goal of improving gout outcomes and its comorbidities together, this study will not only generate immediately actionable evidence on the central outcome of SU, the causal biomarker of gout, but also key data on inflammatory markers, flares, and medication adherence in SGLT2i and placebo to inform future trials.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ana D Fernandes, MA; Phone Number: 617-643-2140; Email: adfernandes@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Hyon K Choi, MD; Phone Number: 6177265650; Email: hchoi@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Provision of signed and dated informed consent form.
2. Fulfilling American College of Rheumatology [ACR]/European Alliance of Associations for Rheumatology [EULAR] gout criteria
3. 1+ gout flares in last 12 months
4. Serum urate level ≥ 6mg/dl
5. Males and females; Age 18-80
6. Willingness to adhere to the study intervention procedures.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Estimated Glomerular Filtration Rate [eGFR] <20ml/min
2. Colchicine or nonsteroidal anti-inflammatory drug [NSAID] prophylaxis
3. active cardiovascular disease [CVD], type-1 diabetes
4. pregnant and lactating women
5. Presence of a condition(s) or diagnosis, either physical or psychological, or physical exam finding that precludes participation. [History of ketoacidosis, end-stage or decompensated liver disease, active cancer]
6. Use of anti-obesity drugs
7. Basal-bolus or multiple daily injection insulin regimens, or loop diuretics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin 10mg; Participants in this arm will take empagliflozin 10mg daily	Drug: Empagliflozin 10 mg; For the empagliflozin arm, participants will take 10 mg daily.; Other Names: Jardiance
Placebo Comparator: Placebo; Participants in this arm will take a placebo daily	Drug: Placebo; Participants in the placebo arm will take a placebo daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Urate Change	Change in serum urate [SU] levels as compared with controls at Week 12. SU levels will be obtained at screening and Week 4, 8, and 12.	Screening to three months of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in highly selective C-reactive protein (hsCRP)	hs-CRP levels will be measured at screening and Week 12	Screening to three months of follow-up
Gout flares	Gout flares will be ascertained using the Gaffo criteria, which requires presence of three or more out of the four items included in the flare diary and asked at each study visit: 1) subject-defined gout-flare, 2) pain at rest >3 on a 0-10 numeric scale, 3) presence of at least one swollen joint, and 4) presence of at least one warm joint.	Screening to three months of follow-up
Medication Adherence	Adherence to empagliflozin or placebo, defined by taking 80% or more of the dispensed doses and calculated by the number of pills taken (pills dispensed - pills counted).	Baseline to three months of follow-up
Changes in Interleukin 6 [IL-6]	IL-6 levels will be measured at screening and 12 weeks.	Screening to three months of follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Measures (36-Item Short Form Survey)	The 36-Item Short Form Survey [SF-36] will be administered at screening and eight weeks later to measure quality of life measures	Screening to two months of follow-up
Quality of Life Assessment [GAQ]	The Gout Assessment Questionnaire [GAQ] will be administered at screening and every monthly visit for the full three month period to assess quality of life in specific regards to gout outcomes.	Screening to three months after baseline
Tophi Measurement	If tophi are present in participants at screening, tophi will be measured for the maximum diameter of the longest tophus using a Vernier caliper and the total number and sites of tophi.	Screening
Work Productivity and Activity Impairment Questionnaire [WPAI]	Participant absences from work and other work-related outcomes will be measured at every visit from screening to the final visit twelve weeks later	Screening to three months of follow-up

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Hyon K Choi, MD, DrPH, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Gout; Hyperuricemia; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; empagliflozin
• Other Study ID Numbers: 2024P003219; 1R61AR084188-01A1 (U.S. NIH Grant/Contract: NIH-NIAMS National Institute of Arthritis and Musculoskeletal and Skin Disease)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes