麻豆传媒

Terlipressin (Terlivaz) reduced the need for renal replacement therapy (RRT) in patients with type 1 hepatorenal syndrome (HRS) who underwent liver transplant, extended follow-up of the phase III trial showed.

In the analysis of 75 patients, HRS reversal was significantly greater among those who received terlipressin, at 37% compared with 14% with placebo (P=0.021), though the advantage in verified reversals with terlipressin did not reach statistical significance (30% vs 17%, respectively; P=0.168), reported K. Rajender Reddy, MD, of the University of Pennsylvania in Philadelphia, at the American College of Gastroenterology annual meeting.

Need for RRT with injectable terlipressin -- a synthetic vasopressin analog that landed an FDA approval in HRS last month -- was significantly lower both pretransplant (30% vs 62% with placebo; P=0.007) as well as at 6 months and 12 months post-transplant:

• 6 months: 20% vs 46% (P=0.017)
• 12 months: 16% vs 46% (P=0.009)

"Treatment with terlipressin improves renal function pre- and post-liver transplant, and thus decreases the need for renal replacement therapy," Reddy told 麻豆传媒. "Thus, healthcare utilization benefits as well as patient care outcomes."

Overall survival was numerically higher in the terlipressin group at 1 year post-liver transplant (94% vs 83%, P=0.093), said Reddy.

HRS is a type of acute kidney injury in patients with end-stage liver disease that is characterized by a rapid onset of renal failure. While liver transplantation remains the only definitive treatment for HRS, renal failure often occurs after transplantation, requiring RRT, which is associated with poor outcomes. In the study, RRT included ultrafiltration, intermittent hemodialysis, continuous hemofiltration or hemodialysis, peritoneal dialysis, or other techniques.

As has been , CONFIRM met its primary endpoint in the overall study population of patients with HRS, showing that treatment with terlipressin led to a significantly greater proportion of patients with verified reversal -- defined as two consecutive serum creatinine values of 1.5 mg/dL or less measured at least 2 hours apart, along with survival without RRT for a minimum of 10 days.

In the primary analysis, however, RRT outcomes were only measured up through 30 days, said Reddy.

For the current analysis, researchers looked at the subgroup of 75 liver transplant recipients (median age 56-57; over 60% men) with type 1 HRS in CONFIRM. This included 46 patients assigned to 1 mg of terlipressin and 29 assigned to placebo (the study had a 2:1 randomization). Both groups received treatment for 14 days and also received concomitant albumin and an intravenous bolus every 6 hours for up to 14 days.

About half of the patients had prior infection, 28% had alcoholic hepatitis, and 9-21% had grade 3 acute-on-chronic liver failure (ACLF). Patients mean baseline serum creatinine was 3.3-3.7 mg/dL.

No significant difference was seen between groups in the frequency of RRT before transplantation, at a median of 2.5 in the study group versus 6.0 in the placebo group (P=0.75).

Five patients underwent a simultaneous liver-kidney transplant, including three in the terlipressin group and two in the placebo group.

Incidence of adverse and serious adverse events was similar between groups. Four terlipressin patients and one placebo patient discontinued treatment because of adverse events.

"There's one adverse event that always is looked for, which is acute respiratory failure, and in this population these events were no different numerically," Reddy said.

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