Operational aspects of terminating the doxazosin arm of The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, practice-based trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The double-blind, active-controlled component of ALLHAT was designed to determine whether the rate of the primary outcome-a composite of fatal coronary heart disease and nonfatal myocardial infarction-differs between diuretic (chlorthalidone) treatment and each of three other classes of antihypertensive drugs: a calcium antagonist (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin) in high-risk hypertensive persons ages 55 years and older. In addition, 10,377 ALLHAT participants with mild to moderate hypercholesterolemia were also enrolled in a randomized, open-label trial designed to determine whether lowering serum LDL cholesterol with an HMG CoA reductase inhibitor (pravastatin) will reduce all-cause mortality as compared to a control group receiving "usual care." In January 2000, an independent data review committee recommended discontinuing the doxazosin treatment arm. The NHLBI director promptly accepted the recommendation. This article discusses the steps involved in the orderly closeout of one arm of ALLHAT and the dissemination of trial results. These steps included provisional preparations; the actual decision process; establishing a timetable; forming a transition committee; preparing materials and instructions; informing 65 trial officers and coordinators, 628 active clinics and satellite locations, 313 institutional review boards, over 42,000 patients, and the general public; reporting detailed trial results; and monitoring the closeout process. Control Clin Trials 2001;22:29-41
Pressel
S L
SL
The University of Texas Health Science Center School of Public Health, Houston, TX, USA. pressel@utsph.uth.tmc.edu
Davis
B R
BR
Wright
J T
JT
Geraci
T S
TS
Kingry
C
C
Ford
C E
CE
Piller
L B
LB
Bettencourt
J
J
Kimmel
B
B
Lusk
C
C
Parks
H
H
Simpson
L M
LM
Nwachuku
C
C
Furberg
C D
CD
D016907:Adverse Drug Reaction Reporting Systems; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D003327:Coronary Disease / Q000401:mortality / Q000517:prevention & control*; D016208:Databases, Factual; D004311:Double-Blind Method; D017292:Doxazosin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D006937:Hypercholesterolemia / Q000401:mortality / Q000517:prevention & control*; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States
D000959:Antihypertensive Agents; D017035:Pravastatin; D017292:Doxazosin