Satoru Muto1, Haruna Kawano2, Eiji Higashihara3, Ichiei Narita4, Yoshifumi Ubara5, Takayuki Matsuzaki6, John Ouyang7, Vicente E Torres8, Shigeo Horie9. 1. Department of Urology, Teikyo University School of Medicine, Tokyo, Japan. 2. Department of Urology, Juntendo University Graduate School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo, 113-8431, Japan. 3. Department of ADPKD Research, Kyorin University School of Medicine, Tokyo, Japan. 4. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 5. Nephrology Center and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan. 6. Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan. 7. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA. 8. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. 9. Department of Urology, Juntendo University Graduate School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo, 113-8431, Japan. shorie@juntendo.ac.jp.
Abstract
BACKGROUND: Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKD patient population. METHODS: The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change. RESULTS: The tolvaptan and placebogroups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4-2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9-6.2) in the placebo group (P < 0.001). The annual estimated glomerular filtration rate change was -3.83 mL/min/1.73 m(2) in the tolvaptan group and -5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m(2) (95 % CI 0.41-2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group. CONCLUSIONS: Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).
RCT Entities:
BACKGROUND: Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKDpatient population. METHODS: The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change. RESULTS: The tolvaptan and placebo groups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4-2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9-6.2) in the placebo group (P < 0.001). The annual estimated glomerular filtration rate change was -3.83 mL/min/1.73 m(2) in the tolvaptan group and -5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m(2) (95 % CI 0.41-2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group. CONCLUSIONS: Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).
Entities:
Keywords:
Autosomal dominant polycystic kidney disease; Japanese population; Kidney function decline; TEMPO 3:4 trial; Tolvaptan; Total kidney volume
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