Kwang-Il Kim1, Mi-Seung Shin2, Sang-Hyun Ihm3, Ho-Joong Youn4, Ki-Chul Sung5, Shung Chull Chae6, Chang-Wook Nam7, Hong Seog Seo8, Seong-Mi Park9, Moo-Yong Rhee10, Moo Hyun Kim11, Kwang Soo Cha12, Yong-Jin Kim13, Jae-Joong Kim14, Kook Jin Chun15, Byung-Su Yoo16, Sungha Park17, Eun-Seok Shin18, Dong-Soo Kim19, Doo Il Kim20, Kye Hun Kim21, Seung-Jae Joo22, Jin-Ok Jeong23, Jinho Shin24, Cheol Ho Kim25. 1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 2. Division of Cardiology, Gachon University Gil Medical Center, Incheon, Republic of Korea. 3. Department of Internal Medicine, Bucheon St. Mary׳s Hospital, College of Medicine, The Catholic University of Koreau, Bucheon, Republic of Korea. 4. Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 5. Division of Cardiology, Department of Medicine Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 6. Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea. 7. Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea. 8. Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea. 9. Division of Cardiology, Korea University College of Medicine, Seoul, Republic of Korea. 10. Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea. 11. Department of Cardiology, Dong-A University Hospital, Busan, Republic of Korea. 12. Department of Cardiology, Pusan National University Hospital, Busan, Republic of Korea. 13. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 14. Division of Cardiology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. 15. Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea. 16. Division of Cardiology, Wonju Severance Christian Hospital, Wonju, Republic of Korea. 17. Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei Health System, Seoul, Republic of Korea. 18. Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine,Ulsan, Republic of Korea. 19. Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea. 20. Department of Internal Medicine, Haeundae Paik Hospital, Busan, Republic of Korea. 21. Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea. 22. Department of Internal Medicine, Jeju National University Hospital, Jeju, Republic of Korea. 23. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea. 24. Division of Cardiology, Hanyang University Hospital, Seoul, Republic of Korea. 25. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address: cheolkim@snu.ac.kr.
Abstract
PURPOSE: The goal of this study was to evaluate whether the blood pressure-lowering efficacy of fimasartan/amlodipine combination therapy was superior to that of fimasartan monotherapy after 8 weeks of treatment in patients with hypertension who had failed to respond adequately to fimasartan monotherapy. METHODS: This trial was a randomized, double-blind, multicenter, Phase III clinical study. Patients who failed to respond after 4 weeks of treatment with 60 mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) ≥140 mm Hg) were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine 60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline to week 8. Secondary end points included the change in SiSBP from baseline to week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4 and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP ≥20 mm Hg) or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events were also assessed. FINDINGS: Of 143 patients randomized to treatment, 137 patients who had available efficacy data were analyzed. The mean age of patients was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg, respectively. In the fimasartan/amlodipine combination group, a greater reduction in SiSBP from baseline to week 8 was observed compared with the fimasartan group (7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4 weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P < 0.0001). At week 8, the response rate was significantly higher in the fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P < 0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine (79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug reactions were observed in 9 patients (6.3%), with no significant differences between treatment groups. There were no serious adverse events associated with the study drugs. IMPLICATIONS: Fimasartan/amlodipine combination therapy exhibited superior efficacy in reducing blood pressure, with no increase in adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov identifier: NCT02152306.
RCT Entities:
PURPOSE: The goal of this study was to evaluate whether the blood pressure-lowering efficacy of fimasartan/amlodipine combination therapy was superior to that of fimasartan monotherapy after 8 weeks of treatment in patients with hypertension who had failed to respond adequately to fimasartan monotherapy. METHODS: This trial was a randomized, double-blind, multicenter, Phase III clinical study. Patients who failed to respond after 4 weeks of treatment with 60 mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) ≥140 mm Hg) were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine 60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline to week 8. Secondary end points included the change in SiSBP from baseline to week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4 and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP ≥20 mm Hg) or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events were also assessed. FINDINGS: Of 143 patients randomized to treatment, 137 patients who had available efficacy data were analyzed. The mean age of patients was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg, respectively. In the fimasartan/amlodipine combination group, a greater reduction in SiSBP from baseline to week 8 was observed compared with the fimasartan group (7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4 weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P < 0.0001). At week 8, the response rate was significantly higher in the fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P < 0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine (79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug reactions were observed in 9 patients (6.3%), with no significant differences between treatment groups. There were no serious adverse events associated with the study drugs. IMPLICATIONS: Fimasartan/amlodipine combination therapy exhibited superior efficacy in reducing blood pressure, with no increase in adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov identifier: NCT02152306.