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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 7, 2015; 21(41): 11584-11596
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11584
Table 1 Main characteristics of randomized double-blind, placebo-controlled trials on vaptans for patients with liver cirrhosis
Ref.V2RADoseAdditional diureticsMax treatment durationNo of patients vaptan(control)Efficacy outcomeMain results
Guyader et al[54]Lixivaptan25, 50, 100, 200, 300 mg/dNone (withheld for 48 h)24 h22 (5)Daily urine output, urine osmolality, serum osmolality, serum NaA significant dose-related increase in daily urine output and a dose-related decrease in urine osmolality together with significant increases in serum osmolality, Na, and vasopressin levels
Gerbes et al[55]Lixivaptan100, 200 mg/dYes? (no detailed information available)7 d40 (20)Serum sodium concentration, urine osmolality, body weightNormalization of serum Na 27% (100 mg/d group) 50% (200 mg/d group); a significant reduction in urine osmolality and body weightFluid intake was restricted to 1000 mL/d
Wong et al[56]Lixivaptan50, 250, 500 mg/dYes8 d25 (8)Free water clearance, serum sodiumSignificant dose related increases in free water clearance and serum Na without changes in orthostatic blood pressure and serum creatinine levelsFluid intake was restricted to 1500 mL/d
Schrier et al[63]Tolvaptan15, 30, 60 mg/dYes30 d63 (57) Salt 1 and Salt 2 study including other causes of hyponatremiaSerum NaEffective in increasing serum Na concentrations at day 4 and day 30
Thuluvath et al[58]RWJ-3516471, 2, 5 mg (single oral doses)Spironolactone 100 mg/d + furosemide 40 mg/d24 h18 (6)Urine volume, free water excretion, urine osmolalityIncreases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose-dependent manner reaching the statistical significance at the 5-mg doseNo changes in either serum chemistry or plasma AVP and renin levels
Ginès et al[59]Satavaptan5, 12.5, 25 mg/dSpironolactone 100 mg/d14 d82 (28)Body weight, abdominal girth, serum NaReduction in body weight and abdominal girth with improvements in serum Na
Ginès et al[60]Satavaptan5, 12.5, 25 mg/dSpironolactone 100 mg/d + furosemide 20-25 mg/d14 d113 (35)Change in body weight The percentage of patients with a weight loss > 2 kgSignificant reduction in body weight; percentage of patients with a weight loss > 2 kg was greater
Wong et al[61]Satavaptan5, 12.5, 25 mg/dSpironolactone 100 mg/d12 wk115 (36)Prevention of recurrent ascites after LVP (1) median time to first paracentesis (2) frequency of paracenteses (3) mean increase in ascitesSignificant decrease in the frequency of paracenteses; No significant difference of mean increase in ascites
Cárdenas et al[64]Tolvaptan15, 30, 60 mg/dSpironolactone < 200 mg/d + furosemide < 80 mg/d30 d63 (57)Serum Na (average daily area under the curve for serum Na); mental component summary scores of the SF-12 health surveyImprovement in serum Na levels and patient-reported health status without severe adverse effectsSub-analysis of the SALT-1 and SALT-2 trials
Wong et al[62]Satavaptan5, 10 mg/dStudy 1 (None); Study 2 (one or more diuretics); Study 3 (withheld during the first 12 wk)52 wk720 (478)Prevention of recurrent ascites after LVP (1) cumulative number of LVPs during the first 12 wk (2) reccurrence of ascites, defined as LVP and/or weight increase of > 4 kg (3) cumulative increase in ascites estimatedNot more effective than placebo in the control of ascites in any of the populations studied as estimated by the primary efficacy endpoints; slight advantages noted in delaying ascites formation and improvement of serum Na concentration in patients with hyponatremia(Study 3) a higher rate of all-cause mortality, mostly associated with complications of cirrhosis in combination with diuretics
Okita et al[67]Tolvaptan7.5, 15 or 30 mg/dFurosemide ≥ 40 mg/d + spironolactone ≥ 25 mg/d or furosemide ≥ 20 mg/d + spironolactone ≥ 50 mg/d7 d77 (27)Body weight, abdominal circumference7.5-30 mg/d reduced body weight and abdominal circumference 7.5 mg/d showed the maximum changes together with preferable tolerability
Sakaida et al[68]Tolvaptan7.5 mg/dfurosemide ≥ 40 mg/d + spironolactone ≥ 25 mg/d or furosemide ≥ 20 mg/d + spironolactone ≥ 50 mg/d7 d84 (80)Change in body weight from baseline; changes in abdominal circumference and ascites volume: improvement rates of lower limb edema and ascites-related clinical symptomschange in body weight; -0.44 kg in the placebo group vs -1.95 kg in the tolvaptan group; higher improvement rates of limb edema and ascites-related clinical symptomsImprove hyponatremia and derease body weight regardless of serum albumin level