Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension
Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension
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DOI：
10.1016/s0895-7061(96)00323-8
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发表时间：
1997-01-01
影响因子：
3.2
通讯作者：
Battikha, JP
中科院分区：
文献类型：
--
作者：
Pool, JL;Cushman, WC;Battikha, JP
血管紧张素转换酶（ACE）抑制剂和噻嗪类利尿剂联合治疗高血压优于单药治疗。以前的研究设计往往不足以证明这些降压药之间的相互作用的细节。本研究采用改良的4 × 4析因随机、双盲、安慰剂对照、平行组设计，研究了17种不同剂量的福辛普利（Fos）（一种次膦酸衍生的ACE抑制剂）和氢氯噻嗪（HCTZ）在550例轻中度高血压患者中的疗效。使用两种组分剂量的多项式函数，将这些变量的数据拟合至二次响应曲面模型（QRSM）。使用QRSM，预测实际剂量的8周坐位收缩压（SeSBP）和舒张压（SeDBP）反应，并对未研究的中间剂量进行插值。Fos和HCTZ单独或联合给药可使SeSBP和SeDBP呈剂量相关性降低。使用10 mg Fos + 12.5 mg HCTZ使校正的平均SeDBP降低6.3 mmHg，20 mg Fos + 12.5 mg HCTZ使相同的测量值降低9.1 mmHg。Fos和HCTZ的联合给药产生了相加的抗高血压作用。本研究采用析因设计和QRSM对高血压联合用药进行了研究，准确预测了剂量反应，是一种有价值的临床试验方法。(C)1997年美国高血压杂志有限公司
The combination of angiotensin converting enzyme (ACE) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension. Previous study designs have often been inadequate to demonstrate the details of interactions between these antihypertensive agents. This study used a modified 4 x 4 factorial randomized, double-blind, placebo-controlled, parallel group design to study the efficacy of 17 different doses of fosinopril (Fos), a phosphinic acid derived ACE inhibitor, and hydrochlorothiazide (HCTZ) in 550 patients with mild to moderate hypertension. Data from these variables were fit to quadratic response surface models (QRSM) using polynomial functions in the doses of the two components. Using QRSM, seated systolic (SeSBP) and diastolic blood pressure (SeDBP) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied. Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP. Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg. Coadministration of Fos and HCTZ produced an additive antihypertensive effect. This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology. (C) 1997 American Journal of Hypertension, Ltd.