Pickkers P, et al. - Among critically ill patients with sepsis-associated acute kidney injury, researchers tested the efficacy of human recombinant alkaline phosphatase in improving kidney function. No remarkable improvement was evident in short-term kidney function in these patients with human recombinant alkaline phosphatase vs placebo.

Methods

• Including 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI, an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study (STOP-AKI trial) was performed.
• Enrollment of patients was carried out between December 2014 and May 2017, and patients were followed-up for 90 days; the final date of follow-up was August 14, 2017.
• To establish the optimal dose, recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n=31), 0.8 mg/kg (n=32), or 1.6 mg/kg (n=29) or placebo (n=30) was administered randomly to patients, once daily for 3 days, in the intention-to-treat analysis in part 1 of the trial.
• On the basis of modeling approaches and adverse events, 1.6 mg/kg was identified as the optimal dose.
• Comparison of 1.6 mg/kg (n=82) to placebo (n=86) was done in part 2.
• Time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC_1-7ECC), was considered as the primary end point.
• Also, evaluation of incidence of fatal and nonfatal (serious) adverse events ([S]AEs) was carried out.

Results

• A total of 301 patients were enrolled (men, 70.7%; median age, 67 years [interquartile range {IQR}, 59-73]).
• In the recombinant alkaline phosphatase vs in the placebo group, the observed median ECC increase from day 1 to day 7 was from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2), respectively (absolute difference, 9.5 mL/min [95% CI, −23.9 to 25.5]; P=.47).
• The occurrence of fatal adverse events was reported in 26.3%, 17.1%, 17.4%, and 29.5% patients in the 0.4-mg/kg recombinant alkaline phosphatase group, 0.8-mg/kg group, 1.6-mg/kg group, and in the placebo group, respectively.
• For the 0.4-mg/kg recombinant alkaline phosphatase group, 0.8-mg/kg group, 1.6-mg/kg group, and for the placebo group, the observed rates of nonfatal SAEs were 21.0%, 14.3%, 25.7%, and 20.5%, respectively.