Efficacy and Safety of Oral Conivaptan, a Vasopressin-Receptor Antagonist, Evaluated in a Randomized, Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

Annane, Djillali; Decaux, Guy; Smith, Neila

doi:10.1097/maj.0b013e31817b8148

Cited by 81 publications

(70 citation statements)

References 37 publications

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“…In the other 2 trials, 83 and 74 patients, respectively, received oral conivaptan 40 or 80 mg ⁄ d or placebo in 2 divided doses for 5 days. 29,30 Compared with placebo, increases from baseline in serum sodium and FWC were significantly greater in patients given IV conivaptan, and treatment was welltolerated. 28 Data from all 3 trials were analyzed to determine the efficacy of conivaptan, specifically in patients with hyponatremia and CHF (Figure).…”

Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

“…Randomized controlled trials of both conivaptan and tolvaptan in euvolemic hyponatremia in heart failure supplement 1 • july • august 2010 S16 and hypervolemic hyponatremia have been published and show benefit, acutely in the case of conivaptan [28][29][30] and up to 30 days in the case of tolvaptan. These studies included patients both with and without CHF.…”

Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

“…The efficacy and safety of conivaptan were evaluated in three phase 3 randomized, double-blind, placebo-controlled trials. [28][29][30] In the first trial, patients received a 20-mg intravenous (IV) loading dose of conivaptan, followed by continuous infusion of conivaptan 40 or 80 mg ⁄ d for 4 days or placebo. In the other 2 trials, 83 and 74 patients, respectively, received oral conivaptan 40 or 80 mg ⁄ d or placebo in 2 divided doses for 5 days.…”

Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

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Treatment Options for Hyponatremia in Heart Failure

Goldsmith¹

2010

Congestive Heart Failure

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Hyponatremia is independently associated with adverse outcomes in patients with congestive heart failure (CHF). The primary cause of hyponatremia in CHF is the inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). The binding of AVP to V2 receptors in the renal collecting duct promotes water retention, a process that can lead to dilutional hyponatremia as well as increased ventricular preload. Conventional treatment of hyponatremia in CHF is largely based on water restriction, which is neither effective nor well‐tolerated. V2‐ and dual V1a/V2‐receptor antagonists offer physiologically based treatment for dilutional hyponatremia. Clinical trials in patients with hyponatremia including those with CHF using both selective and nonselective vasopressin antagonists have demonstrated the effectiveness and safety of these agents in correcting this common electrolyte abnormality. Congest Heart Fail. 2010;16(4)(suppl 1):S15–S18. ©2010 Wiley Periodicals, Inc.

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Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

Section: Vasopressin Receptor Antagonism For Hyponatremia In Patientsmentioning

confidence: 99%

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Treatment Options for Hyponatremia in Heart Failure

Goldsmith¹

2010

Congestive Heart Failure

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“…These drugs are contraindicated for the treatment of hypovolemic hyponatremia. The vaptans have been studied in hundreds of patients with euvolemic hyponatremia (i.e., SIAD), and they have not been associated with an increased risk of hypotension compared with placebo [23][24][25][26]. There have been three studies evaluating the use of vaptans for the treatment of hyponatremia in 69 patients in the neuro-intensive care unit, and four patients (6%) developed hypotension as a medication complication [27][28][29].…”

Section: Assessing the Relative Frequency Of Siad Vs Cswmentioning

confidence: 99%

Syndrome of inappropriate antidiuresis and cerebral salt wasting syndrome: are they different and does it matter?

Moritz

2012

Pediatr Nephrol

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“…82,85 Conivaptan has been assessed in randomized double-blinded placebo-controlled clinical trials, only 1 of which used IV conivaptan. 83,[86][87][88] Zeltser and associates used a small cohort of 84 patients with euvolemic or hypervolemic hyponatremia and randomly assigned them to 40 mg/d, 80 mg/d of IV conivaptan, or placebo, with outcomes measures including net increase in sodium levels and time from initial dose to ≥ 4 mEq/L increase. As compared with only 0.8 mEq/L with placebo, IV conivaptan significantly increased serum sodium levels during a 4-day treatment period, with 6.3 mEq/L and 9.4 mEq/L with 40 mg and 80 mg dosages.…”

Section: Clinical Associationsmentioning

confidence: 99%

Hyponatremia: Clinical Associations, Prognosis, and Treatment in Cirrhosis

Sharma²,

Saab³

2012

Exp Clin Transplant

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Hyponatremia has long been associated with worsened clinical outcomes in patients with cirrhosis and those awaiting liver transplant. However, in the last several years, new modalities of therapy, particularly aquaretics known as "vaptans," and comprehensive prognostic models have been increasingly studied in the hopes of bolstering serum sodium levels and altering liver transplant candidate status. To examine the most recent, comprehensive, and pertinent data, a systematic review of both prospective and retrospective studies available on MEDLINE was completed, which provided information detailing clinical associations, treatment, and prognoses seen in those with hyponatremia in cirrhosis. Clinical associations with hyponatremia in cirrhosis including hepatorenal syndrome and hepatic encephalopathy were identified. For hyponatremia in those awaiting liver transplant, tolvaptan is an effective agent in temporarily normalizing serum sodium levels with minimal risk of osmotic demyelination. Prognostic models incorporating serum sodium levels were better able to predict urgency and need for transplant; yet the benefits and posttransplant effects of redefining a liver allocation score have yet to be established. Key words: Hyponatremia, Cirrhosis, Outcomes IntroductionHyponatremia is a common electrolyte disturbance in patients with advanced liver disease. [1][2][3][4] In the setting of cirrhosis, hyponatremia can be classified as either hypovolemic hyponatremia, which occurs in the setting of overtreatment with diuretics or excessive losses from the gastrointestinal tract, or hypervolemic hyponatremia, which results in decreased effective circulating volume from increased arterial from splanchnic vasodilatation leading to excessive secretion of arginine vasopressin. 1,5,6 Hyponatremia can occur both before and after liver transplant. Pretransplant, it is associated with several clinical manifestations of decompensation, 4,7,8 and the degree of hyponatremia may increase the accuracy of the model for end-stage liver disease (MELD) score to predict survival. [8][9][10][11] Treatment of hyponatremia has not been demonstrated to improve survival in patients with advanced liver disease, and rapid correction can lead to life-threatening neurologic complications. 12,13 This systematic review focuses on the prevalence, clinical associations, treatment, and prognosis of hypervolemic hyponatremia in patients with liver disease. An algorithm will be developed to guide management based on best available data. Methods Search strategy and identification of studiesWe searched database MEDLINE for all studies on hyponatremia in the setting of cirrhosis as related to clinical implications, prognosis, and treatment. We used combinations of the key words: "hyponatremia," "sodium," "liver cirrhosis," "prevalence," "incidence," "intensive care units," "hepatorenal syndrome," "ascites," "central pontine myelinolysis," "therapeutics," "prognosis," and "liver Experimental and Clinical Transplantation (2013) 1: 3-11Christine Yu et a...

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Efficacy and Safety of Oral Conivaptan, a Vasopressin-Receptor Antagonist, Evaluated in a Randomized, Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

Cited by 81 publications

References 37 publications

Treatment Options for Hyponatremia in Heart Failure

Treatment Options for Hyponatremia in Heart Failure

Syndrome of inappropriate antidiuresis and cerebral salt wasting syndrome: are they different and does it matter?

Hyponatremia: Clinical Associations, Prognosis, and Treatment in Cirrhosis

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