Meeting NewsVideo

Terlipressin demonstrates ‘major advance’ in hepatorenal syndrome treatment

BOSTON — In this exclusive video from The Liver Meeting 2019, Arun Sanyal, MD, professor of medicine at Virginia Commonwealth University, discusses results of the CONFIRM trial, which demonstrated that terlipressin was effective in improving renal function and achieving hepatorenal syndrome reversal in a significant percentage of patients with hepatorenal syndrome type 1.

“[Terlipressin] has been used for hepatorenal syndrome elsewhere for a long-time, but is not an approved drug for this indication in the U.S.,” Sanyal, who is an investigator in the CONFIRM trial, told Healio Gastroenterology and Liver Disease.

The purpose of the trial was to confirm the efficacy and safety of terlipressin (Mallinckrodt) plus albumin vs. albumin alone for the treatment of HRS-1 in 300 patients with well-defined HRS-1.

Researchers randomly assigned patients in a 2:1 fashion to terlipressin 1 mg intravenously every 6 hours or placebo, plus albumin in both groups.

One hundred ninety-nine patients received terlipressin, while 101 received placebo, with one not being treated.

Incidence of verified HRS reversal, defined as the percentage of patients with two consecutive SCr values of at least 1.5 mg/dL or less at least 2 hours apart, and the percentage of patients alive without renal replacement therapy for at least 10 days after achieving verified HRS reversal, served as the primary endpoint.

In the terlipressin group, 29.1% achieved verified HRS reversal compared with 15.8% of patients receiving placebo.

Overall, 36.2% of patients receiving terlipressin achieved HRS reversal compared with 16.8% of patients receiving placebo (P < .001).

Almost half (44.8%; n = 29) of patients receiving placebo required renal replacement therapy post-liver transplant vs. 19.6% (n = 46) of patients receiving terlipressin.

There were 176 adverse events (88%) reported in the terlipressin arm, while 88 AEs (88.9%) were reported in the placebo arm.

“This represents a major advance in the treatment of type-1 hepatorenal syndrome, which is a lethal complication and frequently the terminal complication of cirrhosis,” Sanyal said. – by Ryan McDonald

Reference: Wong F, et al. LO5. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.

Disclosure: Sanyal reports consulting relationships with 89Bio, Albireo, Affimmune, Allergan, Amra, Ardelyx, BASF, Birdrock, Boehringer Ingelheim, Chemomab, Conatus, Durect, Echosens, Elsevier, ENYO, Fractyl, General Electric, Gilead, Hemoshear, Immuron, Intercept, Janssen, Lilly, Malinckrodt, Nimbus, Nitto Denko, Novartis, Novo Nordisk, OWL, Perspectum, Pfizer, Poxel, Salix, Sanofi, Second Genome, Servier, Takeda, Terns, Teva, Uptodate and Zydus; grant or research support from Bristol-Myers Squibb, Galectin, Merck and Sequana; and holding stocks in Akarna, Exhalenz, Genfit, Indalo and Tiziana. He is employed by Sanyal Bio.

BOSTON — In this exclusive video from The Liver Meeting 2019, Arun Sanyal, MD, professor of medicine at Virginia Commonwealth University, discusses results of the CONFIRM trial, which demonstrated that terlipressin was effective in improving renal function and achieving hepatorenal syndrome reversal in a significant percentage of patients with hepatorenal syndrome type 1.

“[Terlipressin] has been used for hepatorenal syndrome elsewhere for a long-time, but is not an approved drug for this indication in the U.S.,” Sanyal, who is an investigator in the CONFIRM trial, told Healio Gastroenterology and Liver Disease.

The purpose of the trial was to confirm the efficacy and safety of terlipressin (Mallinckrodt) plus albumin vs. albumin alone for the treatment of HRS-1 in 300 patients with well-defined HRS-1.

Researchers randomly assigned patients in a 2:1 fashion to terlipressin 1 mg intravenously every 6 hours or placebo, plus albumin in both groups.

One hundred ninety-nine patients received terlipressin, while 101 received placebo, with one not being treated.

Incidence of verified HRS reversal, defined as the percentage of patients with two consecutive SCr values of at least 1.5 mg/dL or less at least 2 hours apart, and the percentage of patients alive without renal replacement therapy for at least 10 days after achieving verified HRS reversal, served as the primary endpoint.

In the terlipressin group, 29.1% achieved verified HRS reversal compared with 15.8% of patients receiving placebo.

Overall, 36.2% of patients receiving terlipressin achieved HRS reversal compared with 16.8% of patients receiving placebo (P < .001).

Almost half (44.8%; n = 29) of patients receiving placebo required renal replacement therapy post-liver transplant vs. 19.6% (n = 46) of patients receiving terlipressin.

There were 176 adverse events (88%) reported in the terlipressin arm, while 88 AEs (88.9%) were reported in the placebo arm.

“This represents a major advance in the treatment of type-1 hepatorenal syndrome, which is a lethal complication and frequently the terminal complication of cirrhosis,” Sanyal said. – by Ryan McDonald

Reference: Wong F, et al. LO5. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.

Disclosure: Sanyal reports consulting relationships with 89Bio, Albireo, Affimmune, Allergan, Amra, Ardelyx, BASF, Birdrock, Boehringer Ingelheim, Chemomab, Conatus, Durect, Echosens, Elsevier, ENYO, Fractyl, General Electric, Gilead, Hemoshear, Immuron, Intercept, Janssen, Lilly, Malinckrodt, Nimbus, Nitto Denko, Novartis, Novo Nordisk, OWL, Perspectum, Pfizer, Poxel, Salix, Sanofi, Second Genome, Servier, Takeda, Terns, Teva, Uptodate and Zydus; grant or research support from Bristol-Myers Squibb, Galectin, Merck and Sequana; and holding stocks in Akarna, Exhalenz, Genfit, Indalo and Tiziana. He is employed by Sanyal Bio.

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