The Effects of Peroxisome Proliferator-Activated Receptor-Delta Modulator ASP1128 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.
Kidney Int Rep
; 8(7): 1407-1416, 2023 Jul.
Article
in En
| MEDLINE
| ID: mdl-37441472
ABSTRACT
Introduction:
Peroxisome proliferator-activated receptor δ (PPARδ) plays a central role in modulating mitochondrial function in ischemia-reperfusion injury. The novel PPARδ modulator, ASP1128, was evaluated.Methods:
A randomized, double-blind, placebo-controlled, biomarker assignment-driven, multicenter study was performed in adult patients at risk for acute kidney injury (AKI) following cardiac surgery, examining efficacy and safety of a 3-day, once-daily intravenous dose of 100 mg ASP1128 versus placebo (11). AKI risk was based on clinical characteristics and postoperative urinary biomarker (TIMP2)â¢(IGFBP7). The primary end point was the proportion of patients with AKI based on serum creatinine within 72 hours postsurgery (AKI-SCr72h). Secondary endpoints included the composite end point of major adverse kidney events (MAKE death, renal replacement therapy, and/or ≥25% reduction of estimated glomerular filtration rate [eGFR]) at days 30 and 90).Results:
A total of 150 patients were randomized and received study medication (81 placebo, 69 ASP1128). Rates of AKI-SCr72h were 21.0% and 24.6% in the placebo and ASP1128 arms, respectively (P = 0.595). Rates of moderate/severe AKI (stage 2/3 AKI-SCr and/or stage 3 AKI-urinary output criteria) within 72 hours postsurgery were 19.8% and 23.2%, respectively (P = 0.609). MAKE occurred within 30 days in 11.1% and 13.0% in the placebo and ASP1128 arms (P = 0.717), respectively; and within 90 days in 9.9% and 15.9% in the placebo and ASP1128 arms (P = 0.266), respectively. No safety issues were identified with ASP1128 treatment, but rates of postoperative atrial fibrillation were lower (11.6%) than in the placebo group (29.6%).Conclusion:
ASP1128 was safe and well-tolerated in patients at risk for AKI following cardiac surgery, but it did not show efficacy in renal endpoints.
Full text:
1
Database:
MEDLINE
Type of study:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Year:
2023
Type:
Article