Ilofotase alfa, a human recombinant alkaline phosphatase with potential reno-protective effects, was evaluated for efficacy and safety in the REVIVAL phase-3 trial involving sepsis-associated acute kidney injury (SA-AKI) patients. The trial was a double-blinded, randomized-controlled study focusing on patients with SA-AKI, enrolled within 72 hours of vasopressor use and 24 hours of AKI onset. Its primary goal was to assess 28-day all-cause mortality, with secondary goals including the Major Adverse Kidney Events within 90 days (MAKE90), days alive and free of organ support, days alive and out of the ICU by day 28, and time to death by day 90.
The trial involved 650 patients (330 treated with ilofotase alfa and 319 with a placebo). The 28-day and 90-day mortality rates were similar in both groups (27.9% and 33.9% for ilofotase alfa; 27.9% and 34.8% for placebo). The trial was halted due to futility in meeting the primary endpoint of reducing mortality. There were slightly fewer MAKE90 events in the ilofotase alfa group compared to the placebo. Patients in the ilofotase alfa group also had slightly more days alive and free from organ support, and more days alive and out of the ICU by day 28. However, adverse events were reported in 67.9% of ilofotase alfa patients compared to 75% in the placebo group.
In conclusion, ilofotase alfa did not significantly improve 28-day survival rates in critically ill SA-AKI patients, but there may be a reduction in MAKE90 events. The treatment did not raise any safety concerns.