[17] The trial protocol was reviewed and approved by the institutional review board at each trial site, and written informed consent was obtained from all patients after being informed of the trial purpose and the nature of the procedures involved. All authors had access to the study data and had reviewed and approved the final
manuscript. This trial is registered on Clinical Trials.Gov (NCT00479336). This trial enrolled liver cirrhosis patients with ascites despite undergoing combination therapy with a loop diuretic and an anti-aldosterone drug at the doses from at least 7 days prior to ABT-263 cost commencement of trial drug administration, as described below. Prior treatment with diuretics needed to meet either one of the dose criteria Belinostat cost being used in Japan. If the daily dose of furosemide and other loop diuretics were at least 40 mg and equivalent to 40 mg furosemide, respectively, then the daily dose of spironolactone was set at 25 mg. If the daily dose of spironolactone was at least 50 mg, then the daily dose of furosemide and other loop diuretics were set at 20 mg or equivalent to 20 mg furosemide,
respectively.[18] Patients who met the following criteria were randomized to one of the trial groups and allowed to advance to the treatment period to evaluate efficacy of the drug: patients with ascites during pretreatment observation period; patients orally treated with conventional diuretics without change in dose or mode of administration from 7 days before start of trial drug administration until final day of pretreatment observation period; patients with stable bodyweight (±1.0 kg) for 2 days before start of trial drug administration. The patients were between 20 and 80 years of age and were required to be hospitalized from the start MCE of a 3-day pretreatment observation period until completion of a 14-day
post-treatment observation period. Major exclusion criteria were: (i) patients with hepatic encephalopathy (coma scale, ≥II);[19] (ii) patients with poorly controlled hepatocellular carcinoma; (iii) patients requiring new treatment for esophageal or gastric varices; (iv) patients with hemorrhoidal hemorrhage secondary to rectal varices; and (v) patients receiving blood products including albumin preparations. This trial consisted of a 3-day pretreatment observation period (defined as baseline), a 7-day treatment period and a 14-day post-treatment observation period. Trial drugs were administrated to patients after breakfast. Day 1 was defined as the period from the first to the second administration. Days 2–7 were similarly defined. For all variables, data obtained immediately before the start of trial drug administration were used as baseline data. The day that each patient completed or discontinued the administration of trial drugs was defined as the final dosing day.