REVIVAL
Trial question
What is the role of ilofotase alfa in patients with sepsis-associated AKI?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 649
649 patients (237 female, 412 male).
Inclusion criteria: adult patients with sepsis and < 24 hours of AKI requiring vasopressor support for < 72 hours.
Key exclusion criteria: severe CKD; advanced chronic liver disease; acute pancreatitis without proven infection; urosepsis related to suspected or proven urinary tract obstruction; severe burns requiring ICU treatment; severe immunosuppression.
Interventions
N=330 ilofotase alfa (at a dose of 1.6 mg/kg of body weight up to 120 kg, with a fixed dose of 192 mg in patients > 120 kg once daily for 3 consecutive days).
N=319 placebo (matching placebo).
Primary outcome
Death at day 28
27.9%
27.9%
27.9 %
20.9 %
13.9 %
7.0 %
0.0 %
Ilofotase
alfa
Placebo
No significant
difference ↔
No significant difference in death at day 28 (27.9% vs. 27.9%; ARD -0.02, 95% CI -6.9 to 6.9).
Secondary outcomes
Significant decrease in the rate of major adverse kidney event by 90 days (56.7% vs. 64.6%; ARD -7.9, 95% CI -15.4 to -0.4).
No significant difference in the rate of major adverse kidney event by 90 days (36.4% vs. 40.1%; ARD -3.8, 95% CI -11.2 to 3.7).
No significant difference in days alive and discharged from ICU up to day 28 (15 days vs. 10 days; AD 5 days, 95% CI -0.79 to 10.79).
Safety outcomes
No significant difference in serious adverse events.
Significant difference in adverse events (67.9% vs. 75%).
Conclusion
In adult patients with sepsis and < 24 hours of AKI requiring vasopressor support for < 72 hours, ilofotase alfa was not superior to placebo with respect to death at day 28.
Reference
Peter Pickkers, Derek C Angus, Kristie Bass et al. Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL). Intensive Care Med. 2024 Jan;50(1):68-78.
Open reference URL