Clinical trial NCT06674109: SAVE-Care (Sodium Glucose Cotransporter-2 Inhibitors [SGLT2i] As Novel Gout Care) Trial
Official title: SAVE-Care (SGLT2i As Novel Gout Care) Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Gout and Hyperuricemia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2024-11-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum Urate Change
timeFrame: Screening to three months of follow-up
Secondary outcomes:
measure: Changes in highly selective C-reactive protein (hsCRP)
timeFrame: Screening to three months of follow-up
measure: Gout flares
timeFrame: Screening to three months of follow-up
measure: Medication Adherence
timeFrame: Baseline to three months of follow-up
measure: Changes in Interleukin 6 [IL-6]
timeFrame: Screening to three months of follow-up
Other outcomes:
measure: Quality of Life Measures (36-Item Short Form Survey)
timeFrame: Screening to two months of follow-up
measure: Quality of Life Assessment [GAQ]
timeFrame: Screening to three months after baseline
measure: Tophi Measurement
timeFrame: Screening
measure: Work Productivity and Activity Impairment Questionnaire [WPAI]
timeFrame: Screening to three months of follow-up
Locations:
Study officials:
affiliation: Massachusetts General Hospital
name: Hyon K Choi, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
References: