title: A Multicenter, Randomized, Open-Label Trial: Efficacy of Once-Daily Versus Twice-Daily Double-Dose Rabeprazole on Refractory Gastroesophageal Reflux Disease-Related Symptoms and Quality of Life.
abstract: BACKGROUND
  Approximately 20% to 40% of patients with gastroesophageal reflux disease (GERD) are refractory to standard-dose proton-pump inhibitor (PPI) treatment.
  
  
  OBJECTIVE
  We compared the efficacy and quality-of-life effects of 20 mg once daily (QD) versus 10 mg twice daily (BID) rabeprazole (RPZ) in patients with refractory GERD-related symptoms and sleep disturbances.
  
  
  METHODS
  This multicenter, prospective, randomized, open-label study included patients in whom PPI treatment >4 weeks was ineffective. According to the Global Overall Symptom (GOS) scale, PPI-refractory GERD was defined as ≥1 category with >3 points among 10 specific upper gastrointestinal symptoms. Seventy-eight patients were randomly assigned to 20 mg QD and 10 mg BID RPZ groups for 8 weeks. Efficacy was evaluated using self-reported questionnaires, including the GOS scale and Pittsburg Sleep Quality Index (PSQI), whereas quality of life was assessed using the Short-Form 8 Health Survey (SF-8), at 4 and 8 weeks. Patients showing improvement at 8 weeks received follow-up every 4 to 8 weeks.
  
  
  RESULTS
  GOS scale scores were significantly improved at 8 weeks in both groups, with no significant intergroup differences. Although SF-8 scores showed an increasing trend over 8 weeks in both groups, the physical component summaries in the 10 mg BID group significantly improved. The mental component summaries clearly improved in the 10 mg BID group. Of the 74 cases (4 missing), 51 (68.9%) had PSQI scores ≥5.5. PSQI scores remained unchanged during follow-up in both groups. The recurrence rate was not significantly different (46.1% vs 47.1% in the 20 mg QD and 10 mg BID groups, respectively) during the follow-up period at median (interquartile range) 24.0 (30.5) months.
  
  
  CONCLUSIONS
  In patients with refractory GERD, there was no significant difference in GOS scale score, PSQI, or recurrence rate between the groups. With regard to subscores of the SF-8, the 10 mg BID group might be potentially effective.
authors.affiliation: Department of Internal Medicine, Keiyu Hospital, Yokohama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizuki
authors.affiliation: Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tatemichi
authors.affiliation: Sakakibara Clinic, Yokohama, Japan.
authors.forename: Terue
authors.initials: T
authors.lastname: Sakakibara
authors.affiliation: Minatomirai Naika Clinic, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Tokui Medical Clinic, Yokohama, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Zeki
authors.affiliation: Hiranuma Clinic, Yokohama, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohata
authors.affiliation: Matsuo Clinic, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Kawamura Clinic, Yokohama, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawamura
authors.affiliation: Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagata
keywords: proton-pump inhibitor; quality of life; refractory gastroesophageal reflux disease; sleep disturbances