Lupus Nephritis (LN)
Conditions
Keywords
dapagliflozin, SGLT2 inhibitor, safety, feasibility, pilot trial
Brief summary
Lupus nephritis is a chronic and life-threatening autoimmune cause of kidney disease that predominately impacts young people and can lead to kidney failure. Sodium-glucose co-transporter-2 inhibitors, including dapagliflozin, are known to improve outcomes for people with other causes of chronic kidney disease. This pilot and feasibility randomized clinical trial will test the use of dapagliflozin versus placebo in addition to standard of care treatment for patients with early and active lupus nephritis, a group who has not been included in past trials.
Detailed description
This is a pilot and feasibility randomized, double-blind, placebo-controlled trial involving patients with active lupus nephritis. It will be a concealed allocation, blinded randomized controlled trial of dapagliflozin 10 mg/day or matched placebo in a 2:1 allocation ratio (22 subjects active arm: 11 subjects placebo arm), in addition to standard-of-care treatment, for 12 weeks. After informed consent, 33 eligible subjects will be randomized 2:1 to oral dapagliflozin 10 mg/day or identical oral placebo/day for 12 weeks. Study visits will occur at screening (Visit -1), baseline (Visit 0) and weeks 4 (Visit 1), 8 (Visit 2) and 12 (Visit 3). Observational data including laboratory test results obtained in routine clinical care will be collected through 12 months of follow-up. The primary outcomes are: 1. the overall proportion of identified as potentially eligible/pre-screened patients who enroll in the trial; 2. feasibility and completeness of data collection procedures; 3. changes in urine protein-to-creatinine ratio (UPCR) and precision of these estimates from baseline to week 12 in each group; and 4. rates and proportions of serious adverse events and of adverse events of interest, including genitourinary infections and volume depletion.
Interventions
Pilot and feasibility of adding dapagliflozin to standard medical therapy in active lupus nephritis (LN)
DRUGPlacebo
Matching placebo daily with standard of care
Sponsors
Brigham and Women's Hospital
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Pilot and feasibility, concealed allocation, blinded randomized controlled trial of dapagliflozin 10 mg/day or matched placebo in a 2:1 allocation ratio (22 subjects active arm: 11 subjects placebo arm), in addition to standard-of-care treatment, for 12 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* • Age 18-70 years, fulfilling 2012 SLICC or 2019 ACR/EULAR criteria for SLE, with biopsy-proven class III, IV and/or V LN * Active (new or relapsing) LN within the prior six months, with at least one of the following: * Kidney biopsy with activity index \>2 and/or * Active urinary sediment (\>5 RBCs, \>5 WBCs, or cellular casts) * Receiving standard-of-care immunosuppression regimen for active LN, including mycophenolate, cyclophosphamide, belimumab, azathioprine, a calcineurin inhibitor, and/or B cell depleting therapies * Recent or ongoing glucocorticoids use for active LN within the past 6 months * Receiving standard-of-care antimalarial therapy and RAAS blockade, unless contraindicated * Estimated ≥0.5 g/g 24 hr proteinuria or ≥0.3 mg/g 24 hr microalbuminuria at enrollment (on first morning urine) * Ability to given informed consent
Exclusion criteria
* GFR \< 25 ml/min/1.73m2 * Acute kidney injury at study enrollment (\>50 percent rise in creatinine within 90 days) * Type I diabetes, underweight (BMI \<18.5), active malignancy, active infection, or recurrent genitourinary infections * For females: pregnancy, or desiring of pregnancy and not using contraception, or unable to use contraception * Current use of \>1mg/kg/day prednisone equivalent * Current or prior use of SGLT2 inhibitors or GLP-1 receptor agonists
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of eligible enrolled | 3 years | The overall proportion of identified as potentially eligible/pre-screened patients who enroll in the trial |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of data collection | 3 years | We will assess the percent of missing data elements overall at pilot trial completion. |
Countries
United States
Contacts
CONTACTKaren H Costenbader, MD, MPH
CONTACTApril M Jorge, MD
Outcome results
None listed