Terlipressin improves renal outcomes in hepatorenal syndrome: CONFIRM Study
Hepatorenal syndrome (HRS) is a fatal complication of advanced cirrhosis with ascites and liver failure, with nearly 50% of patients dying within 2weeks after the onset. A recent study suggests that terlipressin was more effective than placebo in improving renal function in patients with cirrhosis and HRS-1. However, it was associated with an adverse reaction. The research has been published in The NEW ENGLAND JOURNAL of MEDICINE on March 04, 2021.
The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. Several studies have suggested that vasoconstrictor therapy with terlipressin (a vasopressin-V1 receptor agonist) and concomitant albumin can improve renal function in patients with type 1 HRS. However, some studies have found that terlipressin had no advantage in improving renal function over other drugs or placebo. To fill the knowledge gap, Dr Florence Wong, MBBS, M.D and colleagues conducted a study to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1.
It was a phase 3, randomized, placebo-control trial of 300 patients with HRS-1 and cirrhosis. Researchers randomly assigned patients to receive terlipressin (n=199) or placebo (n=101) for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The major outcome assessed was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10days after the completion of treatment. Researchers also assessed four prespecified secondary endpoints with the Hochberg procedure to account for multiple comparisons.
Key findings of the study were:
• Upon analysis, researchers found that verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group.
• Concerning the prespecified secondary endpoints, they determined the HRS reversal as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days.
• They reported HRS reversal in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group. HRS reversal without renal-replacement therapy by day 30 was 68 (34%) and 17 (17%), respectively.
• They noted HRS reversal among patients with systemic inflammatory response syndrome was 31 of 84 patients in the terlipressin group and 3 of 48 patients in the placebo group. They further noted that the verified reversal of HRS without recurrence by day 30 was 52 and 17 respectively.
• On day 90, they observed that the liver transplantations were performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively.
• They found more adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo.
• They also found that death within 90 days, due to respiratory disorders in 22 patients in the terlipressin group and 2 patients in the placebo group.
The authors concluded, "In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure."
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