| 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; Terkeltaub, Robert; Greene, Tom A.; Inker, Lesley A; Bjursell, Magnus; Perl, Shira; Rikte, Tord; Erlandsson, Fredrik; Perkovic, Vlado |
| Publisher Information: |
Oxford Academic Press |
| Publication Year: |
2023 |
| Collection: |
University of Limerick: Institutional Repository (ULIR) |
| Subject Terms: |
chronic kidney disease; hyperuricaemia; randomized controlled clinical trial; URAT1 inhibitor; verinu; Health sciences; (3) Good Health and Well-Being |
| 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 þ 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 þ 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. ; The SAPPHIRE study is sponsored by AstraZeneca. The sponsor was involved in the study design, writing of the article and the decision to submit the article for publicat |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
School of Medicine; Nephrology Dialysis Transplantation,August 2022 Volume 37, (8), Pages 1461–1471; https://researchrepository.ul.ie/handle/10344/11835; https://doi.org/10.1093/ndt/gfab237 |
| DOI: |
10.34961/researchrepository-ul.23668095 |
| DOI: |
10.1093/ndt/gfab237 |
| Availability: |
https://doi.org/10.34961/researchrepository-ul.23668095; https://researchrepository.ul.ie/handle/10344/11835; https://doi.org/10.1093/ndt/gfab237 |
| Rights: |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| Accession Number: |
edsbas.4E8D4FFC |
| Database: |
BASE |