Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double‐blind, placebo‐controlled trial

SUMMARYBackground: Heart failure (HF) with hypoalbuminemia is associated with poor response to conventional therapy. We investigated whether tolvaptan, a potent aquaretic agent, might be of benefit in HF patients with hypoalbuminemia. Methods: We prospectively enrolled 40 patients hospitalized for HF. Patients received conventional therapy including loop diuretics. We subsequently added tolvaptan in the range of 3.75-15 mg daily and it was discontinued after improvement of HF symptoms. We compared clinical and laboratory data in HF patients with and without hypoalbuminemia (defined as serum albumin <3.0 g/ dL). Results: Tolvaptan was administered in 18 HF patients with hypoalbuminemia (Group A) and 22 HF patients without hypoalbuminemia (Group B). The mean serum albumin was 2.63 AE 0.27 and 3.46 AE 0.25 g/dL, respectively. The average urine output on tolvaptan increased significantly in both groups (1644.4 AE 797.6-3011.6 AE 1453.8 mL/day, P = 0.004; 1459 AE 612.7-2112.2 AE 724.5 mL/day, P = 0.008; respectively). In addition, we observed higher urine output on therapy in Group A than in Group B (P = 0.015). There was a moderate negative correlation between serum albumin and average urine output on tolvaptan (r = À0.42, P = 0.007). Conclusions: The addition of tolvaptan to low dose loop diuretics might be an effective strategy for treatment of HF patients with hypoalbuminemia.

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“…Hypoalbuminemia was common in these patients (average serum albumin levels were around 2.8 g/dL) [11,12].…”

Section: Introductionmentioning

confidence: 92%

The Efficacy of Tolvaptan in Congestive Heart Failure Patients with and Without Hypoalbuminemia: A Pilot Study

Okabe

Yakushiji

Igawa

et al. 2015

Cardiovascular Therapeutics

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“…This therapeutic mechanism has the potential to improve cirrhosisinduced ascites, and may decrease the need for paracentesis, cell-free and concentrated ascites reinfusion therapy, and transjugular intrahepatic portosystemic shunt placement. A phase III trial of tolvaptan in Japan observed a marked reduction in fluid retention in patients with refractory ascites due to cirrhosis (4 …”

Section: Introductionmentioning

confidence: 99%

Tolvaptan is effective in treating patients with refractory ascites due to cirrhosis

et al. 2017

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Abstract. The treatment of refractory ascites due to cirrhosis is a clinical challenge for hepatologists. Tolvaptan, a novel aquaporin modulator, was made available in Japan in 2013 for the treatment of patients with refractory ascites due to cirrhosis. Despite the potential of this drug, few reports are available regarding its clinical use. The aim of the present study was to clarify the efficacy of tolvaptan in patients with refractory ascites due to cirrhosis and to review the clinical outcomes of treatment. Medical records were retrospectively reviewed for 65 patients with refractory ascites due to cirrhosis who were treated daily with 7.5 mg tolvaptan. The median follow-up time, defined as the period between starting tolvaptan and the last clinic visit or date of mortality, was 175 days (interquartile range 56-406). After one week of tolvaptan treatment, the mean weight reduction was 3.4 kg, with a response rate of 69% (45/65). Subsequently, factors associated with the response to tolvaptan were analyzed. On univariate analysis, maintaining serum sodium (Na) ≥140 mEq/l and an estimated glomerular filtration rate (eGFR) ≥55 ml/min were significant predictors of response (P<0.05). On multivariate analysis, hepatitis C virus etiology, maintaining serum Na ≥140 mEq/l and an eGFR ≥55 ml/min were significant predictors of response (P<0.05). Factors associated with survival were also analyzed using the Cox proportional hazard model. On multivariate analysis, responsiveness to tolvaptan was a predictor of long-term survival (P=0.002), and hyperbilirubinemia was associated with short-term survival (P=0.028). Additionally, KaplanMeier analysis with a log-rank test indicated longer survival times in tolvaptan responders than non-responders (P=0.011).In conclusion, tolvaptan was effective in treating patients with refractory ascites due to cirrhosis. In particular, tolvaptan treatment was highly effective for patients with hepatitis C virus etiology and normal serum Na and renal function. Furthermore, response to tolvaptan was associated with longer survival time while hyperbilirubinemia was associated with shorter survival time.

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“…There was a significant reduction in weight in the tolvaptan group, compared with placebo (-1.95 kg vs -0.44 kg; P < 0.0001), and this benefit held true, even in patients with serum albumin <2.5 g/dL. (28) . In summary there is conclusive evidence that serum hyponatremia has strong correlation to the severeity of complication of liver cirrhosis.…”

Section: Hrs Typementioning

confidence: 83%

Association between Serum Sodium Level and Severity of Complications in Liver Cirrhosis

Ibrahim¹

2017

jmscr

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Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double‐blind, placebo‐controlled trial

Cited by 129 publications

References 22 publications

The Efficacy of Tolvaptan in Congestive Heart Failure Patients with and Without Hypoalbuminemia: A Pilot Study

The Efficacy of Tolvaptan in Congestive Heart Failure Patients with and Without Hypoalbuminemia: A Pilot Study

Tolvaptan is effective in treating patients with refractory ascites due to cirrhosis

Association between Serum Sodium Level and Severity of Complications in Liver Cirrhosis

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