The Effect of Terlipressin on Renal Replacement Therapy in Patients with Hepatorenal Syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Velez JCQ
PROVIDER: S-EPMC10482068 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
The Effect of Terlipressin on Renal Replacement Therapy in Patients with Hepatorenal Syndrome.
Velez Juan Carlos Q JCQ Wong Florence F Reddy K Rajender KR Sanyal Arun J AJ Vargas Hugo E HE Curry Michael P MP Gonzalez Stevan A SA Pappas S Chris SC Jamil Khurram K
Kidney360 20230505 8
Similar Datasets
Project description: Not available
| S-EPMC6481608 | biostudies-literature
Project description:Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.
| S-EPMC9827960 | biostudies-literature
Project description:BackgroundPrevious studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF).AimTo assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin.MethodsIn the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90-day mortality.ResultsThe incidence of RF with terlipressin (n = 200) was 9.4% in patients with grades 1-2 ACLF, and 30% with grade 3 ACLF (p = 0.0002); no such difference was observed in placebo-treated patients (n = 99) (6.2% grades 1-2 vs. 0% grade 3 ACLF, p > 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p = 0.01). Baseline predictors of RF with terlipressin were INR (p = 0.011), mean arterial pressure (p = 0.037), and SpO2 (p = 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90-day survival between terlipressin and placebo arms was similar for grades 1-2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) (p = 0.122), mainly related to RF.ConclusionTerlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.
| S-EPMC9804971 | biostudies-literature
Project description:BackgroundHepatorenal syndrome (HRS) is a severe and progressive functional renal failure occurring in patients with cirrhosis and ascites. Terlipressin is recognized as an effective treatment of HRS, but it is expensive and not widely available. Norepinephrine could be an effective alternative. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of norepinephrine compared to terlipressin in the management of HRS.MethodsWe searched the Medline, Embase, Scopus, CENTRAL, Lilacs and Scielo databases for randomized trials of norepinephrine and terlipressin in the treatment of HRS up to January 2014. Two reviewers collected data and assessed the outcomes and risk of bias. The primary outcome was the reversal of HRS. Secondary outcomes were mortality, recurrence of HRS and adverse events.ResultsFour studies comprising 154 patients were included. All trials were considered to be at overall high risk of bias. There was no difference in the reversal of HRS (RR = 0.97, 95% CI = 0.76 to 1.23), mortality at 30 days (RR = 0.89, 95% CI = 0.68 to 1.17) and recurrence of HRS (RR = 0.72; 95% CI = 0.36 to 1.45) between norepinephrine and terlipressin. Adverse events were less common with norepinephrine (RR = 0.36, 95% CI = 0.15 to 0.83).ConclusionsNorepinephrine seems to be an attractive alternative to terlipressin in the treatment of HRS and is associated with less adverse events. However, these findings are based on data extracted from only four small studies.
| S-EPMC4159336 | biostudies-literature
Project description:Background & aimsHepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.MethodsA prospective, randomized, double-blind, placebo-controlled clinical trial of terlipressin was performed. Subjects with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) or placebo plus albumin in both groups. The dose was doubled on day 4 if the serum creatinine (SCr) level did not decrease by 30% of baseline. Treatment was continued to day 14 unless treatment success, death, dialysis, or transplantation occurred. Treatment success was defined by a decrease in SCr level to </=1.5 mg/dL for at least 48 hours by day 14 without dialysis, death, or relapse of HRS type 1.ResultsFifty-six subjects were randomized to each arm. Treatment success with terlipressin was double that with placebo (25% vs 12.5%, P = .093). SCr level improved from baseline to day 14 on terlipressin (-0.7 mg/dL) as compared with placebo (0 mg/dL), P < .009. Terlipressin was superior to placebo for HRS reversal (34% vs 13%, P = .008), defined by decrease in SCr level </=1.5 mg/dL. Overall and transplantation-free survival was similar between study groups; HRS reversal significantly improved survival at day 180. One nonfatal myocardial infarction occurred with terlipressin, but the total adverse event rate was similar to placebo.ConclusionsTerlipressin is an effective treatment to improve renal function in HRS type 1.
| S-EPMC3730280 | biostudies-literature
Project description:Background and objectivesPatients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases.Design, setting, participants, & measurementsPatients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival.ResultsAge at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls.ConclusionsThese data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.
| S-EPMC3513741 | biostudies-literature
Project description:IntroductionEvidence on the comparison of treatments for hepatorenal syndrome-acute kidney injury (HRS-AKI) in a US population is limited. An indirect comparison of terlipressin plus albumin vs midodrine and octreotide plus albumin (MO) may provide further insight into treatment efficacy.MethodsCohorts of patients treated for HRS-AKI characterized by inclusion of patients with serum creatinine (SCr) <5 mg/dL and baseline acute-on-chronic liver failure grades 0-2 and exclusion of patients listed for transplant if model for end-stage liver disease scores ≥35 were pooled from (i) the CONFIRM and REVERSE randomized controlled trials (N = 159 meeting eligibility criteria from N = 216 overall, treated with terlipressin) and (ii) a retrospective review of medical records from 10 US tertiary hospitals (2016-2019; N = 55 treated with MO meeting eligibility criteria from N = 200 overall). The primary end point comparing the 2 cohorts was HRS reversal defined as achieving SCr ≤1.5 mg/dL at least once during the treatment. Covariate balancing propensity scoring was used to adjust for differences in baseline characteristics.ResultsHRS-AKI reversal was achieved in 52.35% of terlipressin-treated patients compared with 20% of MO-treated patients (adjusted mean difference 32.35%, 95% confidence interval [CI] 17.40-47.30, P < 0.0001). Terlipressin-treated patients had increased overall survival (adjusted hazard ratio 0.57, 95% CI 0.35-0.93, P = 0.02) but similar transplant-free survival (adjusted hazard ratio 0.79, 95% CI 0.53-1.17, P = 0.24). Achievement of HRS-AKI reversal was associated with increased OS and TFS regardless of treatment ( P < 0.001).DiscussionConsistent with prior reports, terlipressin plus albumin is more effective in improving kidney function and achieving HRS-AKI reversal than MO plus albumin based on indirect comparison in a US population.
| S-EPMC10749708 | biostudies-literature
Project description:This study assessed the potential advantages of treating hepatorenal syndrome-acute kidney injury (HRS-AKI) with terlipressin versus placebo in the ICU setting.DesignPatients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days.SettingA retrospective analysis of data from the phase III CONFIRM study.ParticipantsAdult patients with HRS-AKI admitted to the ICU.Main outcomes and measuresIn this substudy, we evaluated outcomes of the ICU stay and the need for organ support, including renal replacement therapy (RRT).ResultsAmong 300 patients with HRS-AKI from the CONFIRM study, 45 were treated in the ICU (terlipressin, 31/199 [16%]; placebo, 14/101 [14%]). On ICU admission, baseline demographics were similar across treatment arms, including severity of liver dysfunction. Among patients alive at the end of the ICU stay, those randomized to terlipressin had a significantly shorter median length of ICU stay than placebo (4 vs 11 d; p < 0.001). Terlipressin-treated patients had a significantly larger improvement in renal function from baseline versus placebo (-0.7 vs +0.2 mg/dL; p = 0.001), including when accounting for the interaction between treatment and day-of-patient-admission to the ICU (-0.7 vs +0.9 mg/dL; p < 0.001). Cumulative requirement for RRT through day 90 was improved in the terlipressin arm versus placebo (10/31 [32%] vs 8/14 [57%]; p = 0.12), although not significantly. Of 13 patients who received a liver transplant, five out of five (100%) in the placebo arm needed RRT through day 90 versus five out of eight (63%) in the terlipressin arm.ConclusionsIn this subanalysis of CONFIRM, patients admitted to the ICU with HRS-AKI who received terlipressin were more likely to achieve renal function improvement, based on serum creatinine changes by the end of treatment, and had significantly shorter lengths of ICU stay than patients randomized to the placebo arm.
| S-EPMC10060094 | biostudies-literature
Project description:BackgroundHepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs).MethodsPubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: "hepatorenal syndrome", "terlipressin", "noradrenaline", and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events.Results15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5).ConclusionTerlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.
| S-EPMC11408352 | biostudies-literature
Project description:IntroductionHepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective.MethodsA decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated.ResultsCost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively.ConclusionsThe analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.
| S-EPMC10611877 | biostudies-literature