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Efficacy

The NEJM-published CONFIRM trial was the largest HRS-AKI trial globally to date1

The multicenter, 2:1 randomized, placebo-controlled, double-blind, phase 3 trial evaluated the safety and efficacy of TERLIVAZ + albumin in 300 adults with HRS with rapid reduction in kidney function.2,3

Explore STUDY DESIGN

Primary and secondary end points from CONFIRM

PRIMARY END POINT

More patients treated with TERLIVAZ® achieved the composite primary end point, the most stringent one studied to date1,2

The primary end point, verified HRS reversal, consisted of the following components2:

  • 2 consecutive SCr measurements of ≤1.5 mg/dL (at least 2 hours apart) by day 14 or discharge
  • Alive without RRTa (eg, dialysis) for at least 10 days

OF THE PATIENTS TREATED WITH TERLIVAZ WHO MET THE PRIMARY END POINT, >50% ACHIEVED CONSECUTIVE SCr VALUES OF ≤1.5 mg/dL BY DAY 63

HRS, hepatorenal syndrome; RRT, renal replacement therapy; SCr, serum creatinine.

aRRT refers to any procedure to replace nonendocrine kidney function and includes intermittent hemodialysis, ultrafiltration, continuous hemofiltration, hemodialysis, peritoneal dialysis, and other dialysis and filtration techniques.1

SECONDARY END POINT

TERLIVAZ® demonstrated a higher rate of durability of HRS reversala

HRS, hepatorenal syndrome; RRT, renal replacement therapy; SCr, serum creatinine.

aDurability of HRS reversal (secondary end point) was defined as the percentage of patients who maintained HRS reversal (SCr ≤1.5 mg/dL while on treatment, by day 14, or discharge) without RRT to day 30.2,5

bRRT refers to any procedure to replace nonendocrine kidney function and includes intermittent hemodialysis, ultrafiltration, continuous hemofiltration, hemodialysis, peritoneal dialysis, and other dialysis and filtration techniques.1

SECONDARY END POINT

In patients with SIRS, TERLIVAZ® demonstrated a higher rate of HRS reversal compared to placebo2,a

HR, heart rate; HRS, hepatorenal syndrome; SCr, serum creatinine; SIRS, systemic inflammatory response syndrome.

aSIRS diagnosis required ≥2 of the following criteria: body temperature <36°C or >38°C, HR >90 bpm, respiratory rate >20 breaths per minute or partial pressure of arterial carbon dioxide <4.3 kPa (32 mm Hg), white-cell count <4000 cells per mm3 or >12,000 cells per mm3, or the presence of >10% immature neutrophils (band forms).3

bPatients with an SCr ≤1.5 mg/dL while on treatment, by day 14, or discharge.2

SECONDARY END POINT

Rate of verified HRS reversal without HRS recurrence by day 30a

The difference between groups was not statistically significant.

HRS, hepatorenal syndrome; RRT, renal replacement therapy; SCr, serum creatinine.

aThis secondary end point was defined as the percentage of patients who maintained verified HRS reversal without HRS recurrence by day 30.2

bVerified HRS reversal defined as the percentage of patients achieving 2 consecutive SCr measurements of ≤1.5 mg/dL at least 2 hours apart by day 14 or discharge and are alive without RRT (eg, dialysis) for ≥10 days.2

Other analyses from CONFIRM

POST HOC ANALYSIS FROM CONFIRM

73.6% of patients treated with TERLIVAZ® were RRT free through day 30

This post hoc analysis was done to show RRT incidence in patients in the ITT population who were alive through day 90.

The analysis was retrospective and based on a much smaller population than the full randomized population in the CONFIRM trial.4

Data are descriptive only; conclusions cannot be made from post hoc analyses.

ITT, intent-to-treat; RRT, renal replacement therapy.

OTHER ANALYSIS FROM CONFIRM

Patients who achieved SCr ≤1.5 mg/dL on at least 1 single measurement by day 14 or discharge4,5

Conclusions based on these data are limited.

SCr, serum creatinine.

POST HOC ANALYSIS FROM CONFIRM

Rates of RRT independence before and after liver transplant5

Data are descriptive only; conclusions cannot be made from post hoc analyses.

These post hoc analyses were done to show RRT incidence in patients in the ITT population who received a liver transplant. RRT incidence was assessed pretransplant and posttransplant at day 90. The analyses were retrospective and based on a much smaller population than the full randomized population in the CONFIRM trial.5

ACLF, acute-on-chronic liver failure; ITT, intent-to-treat; MELD, Model for End-Stage Liver Disease; RRT, renal replacement therapy.

TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with ACLF Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ.2

Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks.2

POST HOC ANALYSIS FROM CONFIRM

Reductions in SCr from baseline to day 14 in CONFIRM

Data are descriptive only; conclusions cannot be made from post hoc analyses.

SCr, serum creatinine; SE, standard error.

a“Overall population” refers to the intent-to-treat (ITT) population, which comprised all patients who underwent randomization.3 N values denote the number of subjects at that timepoint and with a baseline measure.4

bLeast squares (LS) mean.

cBased on repeated-measures analysis of covariance with factors of “treatment,” “qualifying SCr,” “prior large volume paracentesis within 14 days of randomization,” and “day,” and the “treatment-by-day” interaction.4

Meanb treatment difference between the groups with interaction was -0.7 mg/dL (0.10)4,c

POST HOC ANALYSIS FROM CONFIRM

TERLIVAZ® treatment stratified by baseline SCr

SCr, serum creatinine.

aPercentage of patients who achieved SCr ≤1.5 mg/dL on at least 1 single measurement by day 14 or discharge.6

Data are descriptive only; conclusions cannot be made from post hoc analyses.

Limitation of use: Patients with SCr >5 mg/dL are unlikely to experience benefit.2

Limitation of analysis: This is a surrogate end point using a single SCr measurement of ≤1.5 mg/dL. Conclusions based on these data are limited.

POST HOC ANALYSIS FROM CONFIRM

Incidence of RRT independence stratified by SCr level

CONFIRM subpopulation analysis

POST HOC ANALYSIS FROM CONFIRM

Verified HRS reversal rates in the subpopulation analysis

Data are descriptive only; conclusions cannot be made from post hoc analyses.

HRS, hepatorenal syndrome; RRT, renal replacement therapy; SCr, serum creatinine.

aVerified HRS reversal was the multicomponent primary end point for CONFIRM, defined as 2 consecutive SCr values ≤1.5 mg/dL (at least 2 hours apart) by day 14 or discharge and alive without RRT (eg, dialysis) for ≥10 days.2

For more information about the parameters, review the CONFIRM subpopulation parameters.

POST HOC ANALYSIS FROM CONFIRM

Durability of HRS reversal rates in the subpopulation analysis

Data are descriptive only; conclusions cannot be made from post hoc analyses.

HRS, hepatorenal syndrome; SCr, serum creatinine.

aThe percentage of patients who maintained durability of HRS reversal (SCr ≤1.5 mg/dL while on treatment, by day 14, or discharge) without renal replacement therapy (eg, dialysis) to day 30.2,5

For more information about the parameters, review the CONFIRM subpopulation parameters.

POST HOC ANALYSIS FROM CONFIRM

SCr reduction to ≤1.5 mg/dL in the subpopulation analysis

Data are descriptive only; conclusions cannot be made from post hoc analyses.

SCr, serum creatinine.

aThe percentage of patients who achieved SCr ≤1.5 mg/dL on at least 1 single measurement by day 14 or discharge.5

Limitation of analysis: This is a surrogate end point using a single SCr measurement of ≤1.5 mg/dL. Conclusions based on these data are limited.

For more information about the parameters, review the CONFIRM subpopulation parameters.

POST HOC ANALYSIS FROM CONFIRM

RRT independence rates in the subpopulation analysis

Data are descriptive only; conclusions cannot be made from post hoc analyses.

ITT, intent-to-treat; RRT, renal replacement therapy.

aThis post hoc analysis was done to show RRT incidence in patients in the ITT population and mitigated subpopulation who were alive through day 90.4

For more information about the parameters, review the CONFIRM subpopulation parameters.
+

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE

  • TERLIVAZ® may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ.

  • Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%.

INDICATION

TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.

LIMITATION OF USE

Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.

Contraindications

TERLIVAZ is contraindicated:

  • In patients experiencing hypoxia or worsening respiratory symptoms.

  • In patients with ongoing coronary, peripheral, or mesenteric ischemia.

Warnings and Precautions

  • Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms.

    Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure.

  • Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks.

  • Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions.

  • Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus.

Adverse Reactions

  • The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.

Please see full Prescribing Information, including BOXED WARNING.

References: 1. Jamil K, Pappas SC, Wong F, Sanyal AJ. Verified hepatorenal syndrome reversal as a robust multi-component primary end point: the CONFIRM study trial design. Open Access J Clin Trials. 2019;11:67-73. doi:10.2147/ OAJCT.S224974 2. TERLIVAZ® (terlipressin). Prescribing Information. Bridgewater, NJ: Mallinckrodt Hospital Products Inc. 3. 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. doi:10.1056/NEJMoa2008290 4. Data on File - Ref-05035. Keenova Therapeutics. 5. Center for Drug Evaluation and Research. Application number: 0222310rigls000. Accessed January 20, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/0222310rig1sOOOlntegratedR.pdf 6. Wong F, Curry MP, Reddy KR, et al. The CONFIRM Study: a North American randomized controlled trial (RCT) of terlipressin plus albumin for the treatment of hepatorenal syndrome type 1 (HRS-1). Poster presented at: The American Association for the Study of Liver Diseases Annual Meeting; November 8-12, 2019; Boston, MA.

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