BACKGROUND: In the phase 3, double-blind PROTECT trial (NCT03762850), sparsentan (SPAR), a dual endothelin and angiotensin II receptor antagonist (DEARA), showed efficacy in reducing proteinuria and preserving renal function compared with a maximally tolerated dose of irbesartan (IRB) in patients with immunoglobulin A nephropathy (IgAN). Safety profiles for the two treatments were similar. This analysis aimed to evaluate the effect of SPAR compared with IRB on patient-reported outcomes (PROs) in patients with IgAN enrolled in PROTECT.
METHODS: Adult patients were randomized to receive SPAR or IRB for 110 weeks. The Kidney Disease Quality of Life–36 (KDQOL-36) PRO measure was administered at baseline and at weeks 24, 48, 70, 94, and 110. Changes from baseline in Physical Component Summary, Mental Component Summary, Bodily Pain, and kidney-targeted subscale scores were analyzed using least-squares means from mixed models for repeated measures. A score change of 5 was considered clinically meaningful. Time-to-event endpoints, including first improvement, were analyzed using Cox models.
RESULTS: Baseline KDQOL-36 scores were similar for patients randomized to SPAR and IRB. In general, least-squares mean changes from baseline indicated an improvement in Burden of Kidney Disease (BKD) score (week 110 difference [SPAR − IRB], 5.1; 95% confidence interval [CI], 0.45-9.67; P < 0.05]), while other scores were stable through week 110. Hazard ratios for time to first improvement in BKD score (1.51; 95% CI, 1.15- 1.97) favored SPAR.
CONCLUSIONS: For patients with IgAN, analysis of PROs from the PROTECT trial suggests that patients receiving SPAR have less burden of kidney disease over time and a general trend toward improved health-related quality of life compared with those receiving a maximally tolerated dose of IRB.
