Kazuyuki Suzuki1,2, Ryujin Endo2, Yasuhiro Takikawa2, Fuminori Moriyasu3, Yutaka Aoyagi4, Hisataka Moriwaki5, Shuji Terai4,6, Isao Sakaida6, Yoshiyuki Sakai7, Shuhei Nishiguchi7, Toru Ishikawa8, Hitoshi Takagi9, Atsushi Naganuma9, Takuya Genda10, Takafumi Ichida10, Koichi Takaguchi11, Katsuhiko Miyazawa12, Kiwamu Okita13. 1. Department of Nutritional Science, Morioka University, Iwate, Japan. 2. Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan. 3. Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan. 4. Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 5. Department of Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. 6. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. 7. Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. 8. Department of Gastroenterology, Saiseikai Niigata Daini Hospital, Niigata, Japan. 9. Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan. 10. Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan. 11. Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 12. Clinical Development Department, ASKA Pharmaceutical Co., Ltd, Tokyo, Japan. 13. Shunan Memorial Hospital/Yamaguchi University, Yamaguchi, Japan.
Abstract
AIM: The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. METHODS:Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. RESULTS: In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. CONCLUSION: The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.
RCT Entities:
AIM: The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. METHODS: Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. RESULTS: In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. CONCLUSION: The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia.