| Title: |
Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia. |
| Authors: |
Heerspink, Hiddo J L; Stack, Austin G; Terkeltaub, Robert; Greene, Tom A; Inker, Lesley A; Bjursell, Magnus; Perl, Shira; Rikte, Tord; Erlandsson, Fredrik; Perkovic, Vlado |
| Source: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association ; 37 ; 8 ; 1461 ; 1471 ; United States ; England |
| Publication Year: |
2024 |
| Collection: |
Lenus - Irish Health Publications Archive (HSE - Health Service Executive) |
| Subject Terms: |
URAT1 inhibitor; Chronic kidney disease; hyperuricaemia; randomized controlled clinical trial; verinurad |
| Description: |
Background Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. Methods Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. Conclusions This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
http://hdl.handle.net/10147/642063 |
| DOI: |
10.1093/ndt/gfab237 |
| Availability: |
http://hdl.handle.net/10147/642063; https://doi.org/10.1093/ndt/gfab237 |
| Rights: |
© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. ; Attribution-NonCommercial 4.0 International ; http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.D26C136A |
| Database: |
BASE |