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

Authors

Sabry S. Ayad, Outcomes Research Department, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio.
Thomas Beaver, Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, Gainesville, Fla.
David Corteville, Rochester Regional HealthFollow
Madhav Swaminathan, Department of Anesthesiology, Atrium Health Wake Forest Baptist, Wake Forest University School of Medicine, Winston-Salem, NC.
Ronald G. Pearl, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, Calif.
Shakil Aslam, Angion Biomedica, Uniondale, NY.
Philipp Andreas Csomor, CSL Vifor, Glattbrugg, Switzerland.
Gabriela Alperovich, CSL Vifor, Madrid, Spain.
John Neylan, Angion Biomedica, Uniondale, NY.

Department

Cardiology

Document Type

Article

Publication Title

The Journal of Thoracic and Cardiovascular Surgery

Abstract

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.

First Page

1125

Last Page

1132.e2

DOI

10.1016/j.jtcvs.2024.11.024

Volume

170

Issue

4

Publication Date

10-1-2025

Medical Subject Headings

Humans; Acute Kidney Injury (etiology, prevention & control, diagnosis, blood); Male; Female; Double-Blind Method; Aged; Middle Aged; Cardiac Surgical Procedures (adverse effects); Hepatocyte Growth Factor; Cardiopulmonary Bypass (adverse effects); Treatment Outcome; Creatinine (blood); Time Factors

PubMed ID

39603491

Recommended Citation

Ayad, S. S., Beaver, T., Corteville, D., Swaminathan, M., Pearl, R. G., Aslam, S., Csomor, P. A., Alperovich, G., & Neylan, J. (2025). Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777. The Journal of Thoracic and Cardiovascular Surgery, 170 (4), 1125-1132.e2. https://doi.org/10.1016/j.jtcvs.2024.11.024