TY - JOUR
T1 - Design of the DEFINE trial
T2 - Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib
AU - Cannon, Christopher P.
AU - Dansky, Hayes M.
AU - Davidson, Michael
AU - Gotto, Antonio M.
AU - Brinton, Eliot A.
AU - Gould, A. Lawrence
AU - Stepanavage, Michael
AU - Liu, Sherry Xueyu
AU - Shah, Sukrut
AU - Rubino, Joseph
AU - Gibbons, Patrice
AU - Hermanowski-Vosatka, Anne
AU - Binkowitz, Bruce
AU - Mitchel, Yale
AU - Barter, Philip
N1 - Funding Information:
E. Brinton has received research grant support from Abbott, Merck, Pfizer, Sanofi-Aventis, and Takeda Pharmaceuticals and has served on the advisory board and/or speakers' bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Merck, Novartis, Novo-Nordisk, Bagsværd, Denmark, Pfizer, New York, NY, Takeda, and Wyeth-Ayerst Pharmaceuticals, Madison, NJ.
PY - 2009/10
Y1 - 2009/10
N2 - Background: Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date. Methods: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study. Results: A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.
AB - Background: Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date. Methods: Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study. Results: A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.
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U2 - 10.1016/j.ahj.2009.07.028
DO - 10.1016/j.ahj.2009.07.028
M3 - Article
C2 - 19781408
AN - SCOPUS:70349213361
VL - 158
SP - 513-519.e3
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 4
ER -