Abstract: TH-PO635
Interim Analysis of Dapagliflozin in Inactive Lupus Nephritis Cross-Over Randomized Trial
Session Information
- Glomerular Diseases: Clinical and Epidemiologic Studies
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Vajgel, Gisele, Universidade Federal de Pernambuco, Recife, PE, Brazil
- Silva Miranda Filho, Carlos Renê, Universidade Federal de Pernambuco, Recife, PE, Brazil
- Oliveira, Camila Barbosa Lyra, Universidade Federal de Pernambuco, Recife, PE, Brazil
- Costa, Denise Maria Do Nascimento, Universidade Federal de Pernambuco, Recife, PE, Brazil
- da Silva Júnior, Braziliano Miguel, Universidade Federal de Pernambuco, Recife, PE, Brazil
- de Lima, Camilla Albertina Dantas, Universidade Federal de Pernambuco, Recife, PE, Brazil
- Sandrin-Garcia, Paula S., Universidade Federal de Pernambuco, Recife, PE, Brazil
- Valente, Lucila Maria, Universidade Federal de Pernambuco, Recife, PE, Brazil
Background
Clinical trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated to slow the progression of CKD but excluded Lupus Nephritis (LN) patients. This study will assess efficacy and safety of dapagliflozin in inactive LN with residual proteinuria.
Methods
The present cross-over RCT(RBR-3vcg568) is including adults with chronic LN class III or IV(+/-V), proteinuria >500mg/24h and eGFR >20ml/min in maintenance therapy. RAASi should be stable >4w. We exclude patients with recurrent urinary infections; biopsy with active LN (AI>2) and use of induction therapy in the last 12mo, including CNI; and prednisone >20mg/d. Patients are randomized to receive dapagliflozin 10mg on top of standard of care (SoC) therapy or not. After 24w the groups are switched off. Primary endpoint is reduction of proteinuria compared to baseline at 6 and 12mo. Secondary endpoints are changes in weight and blood pressure and number of infections. The sample size was calculated for 28 patients enrolled for 80% power to detect a 25% relative risk reduction in proteinuria (α=0.05).
Results
From 87 screened class III or V(+/-V) LN patients in maintenance therapy, we excluded 67 due to active LN, low proteinuria or low eGFR. We have included 20 patients that were randomized 1:1. There were 18 (90%) women, mean age was 39.5y (±11.1), 1 (5%) had diabetes, median eGFR was 49.5ml/min (40.8-113.8), median proteinuria was 1133mg/24h (833.8-1749), 1 (5.5%) had low C3 or C4, all patients had SLEDAI <6 and used MMF<2g/day. We analysed 6 and 7 patients from initial dapa and 6 and 4 patients from initial SoC after 3 and 6mo, respectively. Although the sample was not powered to compare the groups, initial results showed lower proteinuria in both groups at 3 and 6mo compared to baseline but did not show differences between them. Dapagliflozin was well tolerated, there were no infection episodes during the follow-up, no weight and blood pressure changes, but 5 (45.4%) patients with dapagliflozin had symptoms of hypotension.
Conclusion
We expect that the complete results of this trial will help to evaluate whether the SGLT2 inhibitor, added to LN maintenance therapy, could safely reduce the residual proteinuria of inactive LN patients.
Funding
- Government Support – Non-U.S.