Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777.

OBJECTIVES

To investigate the safety and efficacy of ANG-3777, a hepatocyte growth factor mimetic, in mitigating the risk of acute kidney injury (AKI) in patients undergoing cardiac surgery with cardiopulmonary bypass.

METHODS

In this double-blind placebo-controlled study (Guard Against Renal Damage [GUARD]), patients were randomized to receive intravenous ANG-3777 2 mg/kg or placebo once daily for 4 days. The primary end point was severity of AKI, measured by mean area under the concentration-time curve on percent increase in serum creatinine from days 2 to 6. Secondary end points included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5.

RESULTS

In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% confidence interval, -6.2 to 8.4; P = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; P = .60) or day 90 (14.7% vs 21.5%; P = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery after treatment with ANG-3777 than placebo. Overall, ANG-3777 was well tolerated, with similar incidences of treatment-emergent adverse events between treatment arms.

CONCLUSIONS

Findings from this study do not support the efficacy of ANG-3777 in preventing the development of AKI after cardiopulmonary bypass.