The FDA approval of TERLIVAZ® was based on the landmark CONFIRM Phase 3 trial1
- The NEJM-published CONFIRM trial was the largest HRS trial globally to date
- The multicenter, 2:1 randomized, placebo-controlled, double-blind trial was designed to evaluate efficacy and safety of TERLIVAZ to treat HRS in adult patients with rapid reduction in kidney function1
- Patients were enrolled based on a diagnosis of HRSa that included rapid reduction in renal function (with trajectory for SCr to double within 2 weeks) to a SCr ≥2.25 mg/dL without sustained improvement in renal function after diuretic withdrawal and albumin challenge1
- After albumin resuscitation and at study randomization, patients had a mean serum albumin of 3.7 g/dL in the terlipressin arm (N=188) and 4.0 g/dL in the placebo arm (N=95)2
HRS, hepatorenal syndrome; NEJM, New England Journal of Medicine; SCr, serum creatinine.
aAdults with liver cirrhosis, ascites, and a diagnosis of HRS with a rapidly progressive reduction in renal function (with trajectory for SCr to double within 2 weeks) to a SCr ≥2.25 mg/dL without sustained improvement in renal function 48 hours after withdrawal of diuretics and volume resuscitation/expansion with albumin.
Patients in the CONFIRM trial had high acuity of illness2,3
|Baseline Assessment||TERLIVAZ + Albumin (n=199)||Placebo + Albumin (n=101)|
|Mean baseline SCr, mg/dL (SD)3||3.5 (1.01)||3.5 (1.06)|
|Mean baseline MAP, mmHg (SD)3||78.7 (12.08)||77.5 (9.36)|
|Mean total bilirubin, mg/dL (SD)3||13.1 (13.52)||15.0 (15.58)|
|Mean baseline MELD score (SD)3||32.7 (6.63)||33.1 (6.16)|
|Baseline Child-Pugh class C [10-15], n (%)2||123 (61.8)||61 (60.4)|
|Baseline ACLF Grade 3, n (%)2||40 (20.1)||18 (17.8)|
- 40% of all patients were transferred to the trial site
- ~60% of subjects failed M&Oc
ACLF, acute-on-chronic liver failure; MAP, mean arterial pressure; MELD, Model for End-stage Liver Disease; M&O, midodrine and octreotide; SCr, serum creatinine.
cMidodrine and octreotide treatment were to be stopped prior to randomization.
Patient characteristics and demographics at baseline3
|TERLIVAZ + Albumin (n=199)||Placebo + Albumin (n=101)|
|Mean age, years (SD)||54.0 (11.34)||53.6 (11.83)|
|Male sex, n (%)||120 (60.3)||59 (58.4)|
|Cause of liver cirrhosis, n (%)|
|Alcohol use||134 (67)||67 (66)|
|Nonalcoholic steatohepatitis||42 (21)||24 (24)|
|Alcoholic hepatitis, n (%)||81 (41)||39 (39)|
|Systemic inflammatory response syndrome, n (%)||84 (42)||48 (48)|
|Serum sodium level, mmol/L||133.1 ± 5.6||133.3 ± 5.5|
TERLIVAZ demonstrated Verified HRS Reversal in significantly more patients as compared to placebo1LEARN MORE ABOUT EFFICACY
INDICATION AND LIMITATION OF USE
TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.
- Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.
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%.
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.
- The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.
- TERLIVAZ® (terlipressin). Prescribing Information. Bridgewater, NJ: Mallinckrodt Hospital Products Inc.
- Data on File. Ref-05035. Mallinckrodt Pharmaceuticals.
- Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021;384:818-828.