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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... 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 × 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. © 1997 American Journal of Hypertension, Ltd. Am J Hypertens 1997;10:117–123 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Hypertension Oxford University Press

Use of the Factorial Design and Quadratic Response Surface Models to Evaluate the Fosinopril and Hydrochlorothiazide Combination Therapy in Hypertension*

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References (12)

Publisher
Oxford University Press
Copyright
© 1997 by the American Journal of Hypertension, Ltd.
ISSN
0895-7061
eISSN
1941-7225
DOI
10.1016/S0895-7061(96)00323-8
Publisher site
See Article on Publisher Site

Abstract

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 × 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. © 1997 American Journal of Hypertension, Ltd. Am J Hypertens 1997;10:117–123

Journal

American Journal of Hypertension – Oxford University Press

Published: Jan 1, 1997

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