Terlipressin is more effective than placebo at improving renal function but it is associated with serious adverse events, including respiratory failure, in adults with cirrhosis and type 1 hepatorenal syndrome (HRS-1), researchers reported in the New England Journal of Medicine.
The phase 3 CONFIRM study sought to determine the efficacy and safety of terlipressin plus albumin in adults with HRS-1. A total of 300 patients were randomly assigned to receive terlipressin plus albumin (n = 199; mean age, 54.0 ± 11.3 years; 60% male) or placebo plus albumin (n = 101; mean age, 53.6 ± 11.8 years; 58% male) for up to 14 days.
The patients received 1 mg of terlipressin or placebo intravenously for 2 minutes every 5.5 to 6.5 hours. According to the study authors, it was strongly recommended that all patients receive albumin (1 g/kg of body weight to a maximum of 100 g on day 1, and 20-40 g/day thereafter).
Verified reversal of HRS, defined as 2 consecutive serum creatinine measurements of 1.5 mg/dL or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment, was the primary end point.
The percentage of patients who had verified reversal of HRS was significantly higher in the terlipressin group compared with the placebo group (32% [63 patients] vs 17% [17 patients], respectively; P =.006).
Among the secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg/dL or less during the first 14 days, occurred in 78 patients (39%) in the terlipressin group and in 18 patients (18%) in the placebo group (P <.001). HRS reversal without renal-replacement therapy by day 30 occurred in 68 patients (34%) in the terlipressin group and in 17 patients (17%) in the placebo group (P =.001).
At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and in 29 participants (29%) in the placebo group.
A total of 176 patients (88%) in the terlipressin group and 88 participants (89%) in the placebo group reported adverse events of any severity, including serious adverse events. The incidence of serious adverse events was higher in the terlipressin group (65%) than in the placebo group (61%).
During the on-treatment period, 9 patients (4%) in the terlipressin group and 1 patient (1%) in the placebo group died. Respiratory failure was the most common cause of death while receiving terlipressin or placebo (6 patients [3%] in the terlipressin group and 0 patients in the placebo group).
By day 90, death occurred in 101 patients (51%) in the terlipressin group and in 45 patients (45%) in the placebo group (difference, 6 percentage points; 95% CI, −6 to 18). Death within 90 days due to respiratory disorders was reported in 22 patients (11%) in the terlipressin group and in 2 participants (2%) in the placebo group.
“The use of terlipressin plus albumin was more efficacious than placebo plus albumin in producing verified reversal of HRS in patients with decompensated cirrhosis and HRS-1,” the investigators stated. “Terlipressin was associated with serious adverse events, including respiratory failure.”
Among several study limitations, the trial was not powered to assess the between-group difference in survival, and a detailed follow-up beyond 90 days that included assessing prespecified outcomes after liver transplantation was not conducted.
“Terlipressin should be used with caution in patients who have the most advanced liver disease,” advised the researchers.
Disclosures: The study was supported by Mallinckrodt Pharmaceuticals. Some of the authors reported affiliations with pharmaceutical companies, including Mallinckrodt Pharmaceuticals. See the original study for a full list of disclosures.
Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021;384(9):818-828.