This Article  • References  • Full text PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (58)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

Application of Factorial Trial Design to a Multicenter Clinical Trial of Combination Therapy

James F. Burris, MD; Matthew R. Weir, MD; Suzanne Oparil, MD; Michael Weber, MD; William J. Cady, PharmD; William H. Stewart, PhD

JAMA. 1990;263(11):1507-1512.

Abstract
This multicenter, factorial-design trial assessed the safety and additive antihypertensive efficacy of a slow-release (SR) formulation of diltiazem hydrochloride given alone or in combination with hydrochlorothiazide for treatment of mild to moderate hypertension. After a 4- to 6-week placebo run-in period, 297 qualifying patients were randomized to receive placebo, 1 of 4 doses of diltiazem SR monotherapy, 1 of 3 doses of hydrochlorothiazide monotherapy, or 1 of 12 possible combinations of diltiazem SR and hydrochlorothiazide for 6 weeks. A dose-related reduction in blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Absolute blood pressures of patients who received combination therapy were lower by an overall mean of 3.0 mm Hg diastolic and 8.0 mm Hg systolic vs diltiazem SR used alone and 3.5 mm Hg diastolic and 4.0 mm Hg systolic vs hydrochlorothiazide used alone. At the largest doses used, 50% of patients achieved goal blood pressure while taking hydrochlorothiazide, 57% while taking diltiazem SR, and 75% while taking combination therapy. Combination therapy was well tolerated. This trial clearly demonstrates that diltiazem SR and hydrochlorothiazide have additive antihypertensive effects.

(JAMA. 1990;263:1507-1512)

Author Affiliations
From the Hypertension Research Unit, Veterans Administration Medical Center, Washington, DC (Dr Burris); the Clinical Research Unit and Division of Nephrology, the Department of Medicine, University of Maryland Hospital, Baltimore (Dr Weir); the Division of Cardiovascular Disease, University of Alabama at Birmingham (Dr Oparil); the Hypertension Center, Veterans Administration Medical Center, Long Beach, Calif (Dr Weber); and Marion Laboratories Inc, Kansas City, Mo (Drs Cady and Stewart). Dr Burris has held contracts with Marion Laboratories; Drs Burris and Weber have spoken at meetings sponsored by Marion Laboratories; and Drs Cady and Stewart are employees of Marion Laboratories.

Footnotes
Reprint requests to NE120 Med-Dent, Georgetown University Medical Center, 3900 Reservoir Rd NW, Washington, DC 20007 (Dr Burris).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Use of diuretics in cardiovascular disease: (2) hypertension
Shah et al.
Postgrad. Med. J. 2004;80:271-276.
ABSTRACT | FULL TEXT  

Effects of low dose versus conventional dose thiazide diuretic on insulin action in essential hypertension
Harper et al.
BMJ 1994;309:226-230.
ABSTRACT | FULL TEXT  

A Multifactorial Trial Design to Assess Combination Therapy in Hypertension: Treatment With Bisoprolol and Hydrochlorothiazide
Frishman et al.
Arch Intern Med 1994;154:1461-1468.
ABSTRACT  

Single-Drug Therapy for Hypertension in Men
Johnston et al.
NEJM 1993;329:1043-1045.
FULL TEXT  

The Effects of Thiazides Plus Calcium Channel Blockers
Cappuccio et al.
JAMA 1990;264:971-972.
ABSTRACT  

Calcium Channel Blockers as Second-Line Therapy in Thiazide-Resistant Hypertension
Prisant and Carr
Arch Intern Med 1990;150:1758-1760.
ABSTRACT