An Open Label, Pilot, Randomized Controlled Trial of Noradrenaline<i>Versus</i>Terlipressin in the Treatment of Type 1 Hepatorenal Syndrome and Predictors of Response

Sharma, Praveen; Kumar, Ashish; Shrama, Brajesh C.; Sarin, Shiv Kumar

doi:10.1111/j.1572-0241.2008.01828.x

Cited by 257 publications

(248 citation statements)

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“…Our observations regarding factors predictive of HRS reversal and survival essentially confirm what has been observed in previous studies,22, 23, 24, 25, 26, 27 with the exception of the absence of a precipitating cause for HRS‐1, absence of prior rifaximin use in the terlipressin group, and male sex in the placebo group – all new observations. The absence of prior rifaximin use as a factor predictive of HRS reversal in the terlipressin group is of interest; it is possible that patients without prior rifaximin exposure are less ill than those receiving rifaximin.…”

Section: Discussionsupporting

confidence: 89%

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies

Sanyal

Boyer

Frederick

et al. 2017

Aliment Pharmacol Ther

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SummaryBackgroundThe goal of hepatorenal syndrome type 1 (HRS‐1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS‐1, where it is available.AimTo compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS‐1.MethodsPooled patient‐level data from two large phase 3, randomised, placebo‐controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90‐day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days.ResultsThe pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between‐group difference in SCr concentration of −53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin‐treated patients.ConclusionsTerlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS‐1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT‐0401, NCT00089570; REVERSE, NCT01143246).

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Section: Discussionsupporting

confidence: 89%

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies

Sanyal

Boyer

Frederick

et al. 2017

Aliment Pharmacol Ther

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“…In small comparative studies, norepinephrine has demonstrated a similar rate of HRS reversal and patient survival when compared with terlipressin [28,29]. Adverse effects between norepinephrine and terlipressin are similar, with reversible cardiac and digital ischemia being the most common adverse events [29]. The cost of norepinephrine therapy is also significantly lower than terlipressin (107 ± 31 versus 1536 ± 40 Euros, P < 0.0001), making it an attractive alternative therapy [28].…”

Section: Norepinephrine Versus Terlipressinmentioning

confidence: 91%

“…Similar to terlipressin, in patients with HRS, norepinephrine effectively improves UOP, sodium excretion, serum sodium concentration, creatinine clearance (CrCl), MAP, plasma renin activity, and aldosterone activity. In small comparative studies, norepinephrine has demonstrated a similar rate of HRS reversal and patient survival when compared with terlipressin [28,29]. Adverse effects between norepinephrine and terlipressin are similar, with reversible cardiac and digital ischemia being the most common adverse events [29].…”

Section: Norepinephrine Versus Terlipressinmentioning

confidence: 96%

Hepatorenal Syndrome

Kiser¹

2014

IJCM

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Hepatorenal syndrome (HRS) is the most serious hepatorenal disorder and one of the most difficult to treat. To date, the best treatment options are those that reverse the mechanisms underlying HRS: portal hypertension, splanchnic vasodilation, and/or renal vasoconstriction. Therefore, liver transplantation is the preferred definitive treatment option. The role of other therapies is predominantly to prolong survival sufficiently to allow patients to undergo transplantation. Terlipressin with the addition of adjunctive albumin volume expansion is the preferred pharmacologic therapy for the treatment of patients with HRS. Norepinephrine and vasopressin are acceptable alternatives in countries where terlipressin is not yet available. For patients with Type II HRS, midodrine plus octreotide appears to be an effective pharmacologic regimen that can be administered outside of an intensive care unit setting. Regardless of chosen vasoconstrictor therapy, careful monitoring is needed to ensure tissue ischemia and severe adverse effects do not occur. Artificial hepatic support devices, renal replacement therapy, and transjugular intrahepatic portosystemic shunt (TIPS) are non-pharmacologic options for patients with HRS. However, hepatic support devices and renal replacement therapies have not yet demonstrated improved outcomes and TIPS is difficult to be employed in patients with Type I HRS due to contraindications in the majority of patients. Despite advances in our understanding of hepatorenal syndrome, the disease is still associated with significant morbidity, mortality, and costs. More evidence is urgently needed to help improve patient outcomes in this difficult-to-treat population.

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“…Alpha-adrenergic agonists, such as norepinephrine [Sharma et al 2008;Singh et al 2012] or midodrine, in combination with octreotide and albumin [Angeli et al 1999;Skagen et al 2009;Wong et al 2004], are a reasonable alternative to terlipressin because of their low cost and wide availability. However, data on their use are limited.…”

Section: Albuminmentioning

confidence: 99%

Treatment and management of ascites and hepatorenal syndrome: an update

Lenz

Buder

Kapun³

et al. 2014

Therap Adv Gastroenterol

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Ascites and renal dysfunction are frequent complications experienced by patients with cirrhosis of the liver. Ascites is the pathologic accumulation of fluid in the peritoneal cavity, and is one of the cardinal signs of portal hypertension. The diagnostic evaluation of ascites involves assessment of its granulocyte count and protein concentration to exclude complications such as infection or malignoma and to allow risk stratification for the development of spontaneous peritonitis. Although sodium restriction and diuretics remain the cornerstone of the management of ascites, many patients require additional therapy when they become refractory to this treatment. In this situation, the treatment of choice is repeated large-volume paracentesis. Alteration in splanchnic hemodynamics is one of the most important changes underlying the development of ascites. Further splanchnic dilation leads to changes in systemic hemodynamics, activating vasopressor agents and leading to decreased renal perfusion. Small alterations in renal function influence the prognosis, which depends on the cause of renal failure. Prerenal failure is evident in about 70% of patients, whereas in about 30% of patients the cause is hepatorenal syndrome (HRS), which is associated with a worse prognosis. Therefore, effective therapy is of great clinical importance. Recent data indicate that use of the new definition of acute kidney injury facilitates the identification and treatment of patients with renal insufficiency more rapidly than use of the current criteria for HRS. In this review article, we evaluate approaches to the management of patients with ascites and HRS.

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An Open Label, Pilot, Randomized Controlled Trial of NoradrenalineVersusTerlipressin in the Treatment of Type 1 Hepatorenal Syndrome and Predictors of Response

Abstract: Noradrenaline may be an effective and safe alternative to terlipressin in improving renal functions. Various baseline parameters and DCD4 can be used to predict response to therapy.

Cited by 257 publications

References 23 publications

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT‐0401 and REVERSE randomised clinical studies

Hepatorenal Syndrome

Treatment and management of ascites and hepatorenal syndrome: an update

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