METHODS: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM).
RESULTS: A total of 532 patients were randomized: Per/Ind/Aml ( n = 262) and Per/Ind + Aml ( n = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated.
CONCLUSIONS: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.
方法:第三阶段,多中心,随机化,双盲,非劣效性研究纳入了患有轻度至中度高血压的中国成年人.经过1个月的培多普利/茚达帕胺双重治疗,收缩压/舒张压血压不受控制(≥140/90mmHg)的患者被随机分为两组,两组分别接受培多普利5mg/茚达胺1.25mg/氨氯地平5mg(Per/Ind/Aml)单药联合治疗(SPC)或培多普利4mg/茚达帕胺1.25mg+氨氯地平5mg(Per/Ind+Aml)治疗6个月.从第2个月起允许增加滴定。主要疗效目标是Per/Ind/Aml在降低2个月时的办公室收缩压方面的非劣效性。次要目标包括SPC对舒张压的有效性,向上滴定功效,和办公室血压控制(收缩压/舒张压<140/90mmHg)。一组患者参加了24小时动态BP监测(ABPM)。
结果:共有532名患者被随机分配:Per/Ind/Aml(n=262)和Per/Ind+Aml(n=269)。总的来说,平均(±SD)年龄为55.7±8.8岁,60.7%为男性,基线时Per/Ind的平均办公室收缩压/舒张压为150.4/97.2mmHg。从基线开始2个月时,两组的收缩压均降低:-14.99±14.46mmHg/Ind/Aml与-14.49±12.87mmHg/IndAml。观察到预定义的非劣效性边缘为4mmHg(P<0.001)。对于所有次要终点,也证明了Per/Ind/AmlSPC的有效性。ABPM在24小时内表现出持续的BP控制。两种治疗均具有良好的耐受性。
结论:Per/Ind/Aml是Per/Ind+Aml的有效替代品,在单一药丸中在24小时内提供至少等效的BP控制,具有可比的安全性。