Teprasiran confers renoprotection in high-risk patients undergoing cardiac surgery

Treatment with the novel small interfering RNA (siRNA) teprasiran appears to cut the incidence, severity, and duration of early acute kidney injury (AKI) in high-risk patients undergoing cardiac surgery, according to the results of a phase II trial.

The trial randomized 360 patients to treatment with a single 10-mg/kg dose of teprasiran or placebo, among whom 341 (mean age 73 years, 72 percent male, median European System for Cardiac Operative Risk Evaluation 2.6 percent) received their doses.

Teprasiran was superior to placebo in terms of the primary endpoint of the incidence of AKI, as determined by serum creatinine, by postoperative day 5 (36.9 percent vs 49.7 percent; relative risk reduction [RRR], 25.8 percent; odds ratio, 0.58, 95 percent confidence interval, 0.37–0.92).

Other endpoints were also better in the active treatment group than in the placebo group. Specifically, AKI severity based on Acute Kidney Injury Network criteria significantly decreased following teprasiran, with RRR values of 18 percent (31.2 percent vs 38.2 percent) for AKI stage 1, 33 percent (3.2 percent vs 4.8 percent) for stage 2, and 63 percent (2.5 percent vs 6.7 percent) for stage 3.

Furthermore, significantly fewer patients on teprasiran vs placebo had AKI that lasted 5 days (7 percent vs 13 percent).

There was no significant difference observed in the composite endpoint of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25-percent reduction in estimated glomerular filtration rate.  

Teprasiran was well tolerated, with no safety issues identified.