A multicenter randomized, double-blinded placebo-controlled phase 2 trial to evaluate safety and efficacy of ilofotase alfa in patients at risk for kidney injury following open heart surgery

Abstract

Acute impairment of kidney function after cardiac surgery is common and associated with an increased morbidity and mortality. Ilofotase alfa has demonstrated potential to attenuate renal injury through its immunomodulatory effects. We evaluated the safety and efficacy of ilofotase alfa in preventing renal functional impairment in cardiac surgery patients. This phase 2, multi-center, randomized, double-blinded, placebo-controlled trial employing a two-arm, parallel-group design randomized adult patients at a high risk of renal functional impairment after on-pump cardiac surgery. Patients with a pre-existent estimated glomerular filtration rate of 25–65 ml/min/1.73m 2 scheduled to undergo complex cardiac surgery were eligible. Patients received two intravenous doses (128 mg) of ilofotase alfa or placebo perioperatively. The primary endpoint was the ratio between the highest serum creatinine levels within five days postoperative relative to the pre-operative level (sCrRatio). The secondary endpoint was major adverse kidney events up to day 60 (MAKE60). In total, 244 patients were randomized of whom 204 received two doses and were included in the trial analysis: 109 patients were treated with ilofotase alfa and 95 received placebo. The mean±SD sCrRatio in the ilofotase alfa group was 1.21±0.42, compared to 1.27±0.50 for placebo (p=0.31). MAKE60 incidence was 15.9% in the ilofotase alfa group and 15.4% in the placebo group (p=0.87). No safety concerns were raised. Administration of ilofotase alfa did not attenuate short- and longer-term renal function loss in patients at a high risk of renal functional impairment after on-pump cardiac surgery. No safety concerns of ilofotase alfa emerged. EUCT Number: 2023-505859-45 US IND Number: 117 605 ClinicalTrials.gov ID: NCT06168799