Improvement in serum creatinine was associated with favorable clinical outcomes in patients with hepatorenal syndrome: A post hoc analysis of the CONFIRM study
Presenter: Juan Carlos Q. Velez, MD, Ochsner Health, New Orleans, LA.
Improvement in Serum Creatinine Was Associated with Favorable Clinical Outcomes in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study. Abstract TH-PO052. Presented Nov 2, 2023.
In a post hoc analysis of the CONFIRM study, significantly more patients with hepatorenal syndrome receiving the vasopressor terlipressin achieved a 30% or more improvement in serum creatinine as compared with those receiving placebo, and through day 90, a 30% or higher improvement in serum creatinine was associated with significantly better clinical outcomes, said study author Juan Carlos Q. Velez, MD, Ochsner Health, New Orleans, LA, in a 2023 Kidney Week poster presentation.
While potentially reversible, hepatorenal syndrome is a life-threatening form of acute kidney injury that occurs in people with liver cirrhosis and ascites. Terlipressin is the only US Food and Drug Administration-approved treatment for adult patients with hepatorenal syndrome and rapid reduction in kidney function, Velez noted. Both the American Association for the Study of Liver Diseases and the American College of Gastroenterology recommend terlipressin as first-line therapy once a diagnosis of hepatorenal syndrome-acute kidney injury has been established.
The phase 3 CONFIRM study included 300 adult patients (mean age about 54 years), with cirrhosis, ascites, hepatorenal syndrome, and a serum creatinine concentration that was 2.25 mg/dL or higher and projected to double within 2 weeks. They were randomized to receive intravenous terlipressin 1 mg every 6 hours or matched placebo, with albumin recommended. Terlipressin dosing was adjusted on day 4 based on the patient’s serum creatinine level relative to treatment initiation: patients with a greater than 30% improvement in serum creatinine were continued on 1 mg every 6 hours, while a dose increase to 2 mg every 6 hours was recommended for patients whose serum creatinine level improved 30% or less from baseline.
More patients treated with terlipressin achieved verified hepatorenal syndrome reversal than those receiving placebo (29.1% with terlipressin, 15.8% with placebo, P = .012). Reversal was defined as 2 consecutive serum creatinine measurements of 1.5 mg/dL or less obtained at least 2 hours apart while receiving treatment up to day 14 or discharge, and alive without renal replacement therapy for at least an additional 10 days.
The CONFIRM investigators stratified the intention-to-treat population according to whether their serum creatinine concentration had improved more than 30% or 30% or less from baseline (day 0 or a prestudy value if the day 0 value was missing) to the end of treatment, and they analyzed the following outcomes: length of intensive care unit (ICU) stay; incidence of renal replacement therapy (RRT); RRT-free survival at days 30, 60, and 90; and survival at day 90.
More patients in the terlipressin than in the placebo group had a greater than 30% improvement in serum creatinine from baseline to the end of treatment (43.7% vs 21.9%, P < .001), Velez reported. Among patients admitted to the ICU, the mean length of stay was shorter among those with greater than 30% serum creatinine improvement, but the difference was not statistically significant (5.8 vs 9.4 days, P = .673). Also, among those who achieved more than 30% serum creatinine improvement, a higher proportion were alive (67.0% vs 42.9%, P < .0001), and alive and RRT-free by day 90 (55.0% vs 20.4%, P <.001).
Velez concluded, “Significantly more patients in the terlipressin group achieved a greater than 30% improvement in serum creatinine versus placebo. Patients with a greater than 30% improvement in serum creatinine had significant improvements in clinical outcomes through day 90.” He added, “Collectively, the results of this post hoc analysis suggest that the reduction in serum creatinine levels associated with terlipressin treatment improves multiple clinical outcomes among patients with hepatorenal syndrome.”