Designs of RADIANCE 1 and 2: carotid ultrasound studies comparing the effects of torcetrapib/atorvastatin with atorvastatin alone on atherosclerosis.
ABSTRACT OBJECTIVE: The RADIANCE studies were designed to assess the effects of torcetrapib/atorvastatin (T/A) compared with atorvastatin alone on slowing atherosclerotic progression in patients with heterozygous familial hypercholesterolemia (RADIANCE 1) or mixed hyperlipidemia (RADIANCE 2), as measured by change in carotid intima-media thickness (CIMT). RESEARCH DESIGN AND METHODS: RADIANCE 1 and 2 were randomized, double-blind, controlled trials with a duration of 2 years. In both studies, eligible subjects began treatment with atorvastatin during a run-in period and were titrated to target LDL-C levels defined by NCEP ATP III guidelines. Subjects then proceeded to a double-blind randomized treatment period where they received one of two regimens: (i) fixed combination T/A (torcetrapib dose, 60 mg), or (ii) atorvastatin alone. In both regimens, the dose of atorvastatin was established during the run-in period (20-80 mg, RADIANCE 1; 10-80 mg RADIANCE 2). B-mode ultrasonography was performed in duplicate at baseline and at end of study, and every 6 months in between. MAIN OUTCOME MEASURES: The primary efficacy measure in both studies was the annualized rate of change in maximum CIMT of 12 pre-defined carotid segments. Further outcome measures included lipid and safety assessments. Current status: The number of subjects randomized was 904 in RADIANCE 1 and 752 in RADIANCE 2. Results are anticipated in 2007.
Article: Lessons from the torcetrapib trials
Conference Paper: Transparent tone-in-band (TTIB) aided GMSK/MSK modem systems[Show abstract] [Hide abstract]
ABSTRACT: The authors propose a scheme which employs BBC (binary block code) coding to allow carrier pilot insertion in GMSK/MSK (Gaussian minimum-shift keying/minimum-shift keying) modems for tone calibration and coherent detection. They analyze the performance of the BBC-coded GMSK/MSK modem and derive a closed-form expression for its performance under Rayleigh fading. The effect of carrier phase noise on the modem's performance in a nonfading channel is investigated. it is found that, in the absence of fading, GMSK signalling with small bandwidth-time product ( BT ) value is more sensitive to carrier phase jitter than that with larger BT . The authors also investigated the performance of a BBC-coded GMSK modem with tone calibration over a Rayleigh fading channel. It is found that the modem is capable of delivering good performance in a Rayleigh fading environment where the more conventional coherent detection would cease to be practical due to its relatively high error floorVehicular Technology Conference, 1989, IEEE 39th; 06/1989
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ABSTRACT: Torcetrapib, an inhibitor of cholesteryl ester transfer protein, may reduce atherosclerotic vascular disease by increasing levels of high-density lipoprotein (HDL) cholesterol. A total of 850 patients with heterozygous familial hypercholesterolemia underwent B-mode ultrasonography at baseline and at follow-up to measure changes in carotid intima-media thickness. The patients completed an atorvastatin run-in period and were subsequently randomly assigned to receive either atorvastatin monotherapy or atorvastatin combined with 60 mg of torcetrapib for 2 years. After 24 months, in the atorvastatin-only group, the mean (+/-SD) HDL cholesterol level was 52.4+/-13.5 mg per deciliter and the mean low-density lipoprotein (LDL) cholesterol level was 143.2+/-42.2 mg per deciliter, as compared with 81.5+/-22.6 mg per deciliter and 115.1+/-48.5 mg per deciliter, respectively, in the torcetrapib-atorvastatin group. During the study, average systolic blood pressure increased by 2.8 mm Hg in the torcetrapib-atorvastatin group, as compared with the atorvastatin-only group. The increase in maximum carotid intima-media thickness, the primary measure of efficacy, was 0.0053+/-0.0028 mm per year in the atorvastatin-only group and 0.0047+/-0.0028 mm per year in the torcetrapib-atorvastatin group (P=0.87). The secondary efficacy measure, annualized change in mean carotid intima-media thickness for the common carotid artery, indicated a decrease of 0.0014 mm per year in the atorvastatin-only group, as compared with an increase of 0.0038 mm per year in the torcetrapib-atorvastatin group (P=0.005). In patients with familial hypercholesterolemia, the use of torcetrapib with atorvastatin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides. (ClinicalTrials.gov number, NCT00136981 [ClinicalTrials.gov].).New England Journal of Medicine 05/2007; 356(16):1620-30. DOI:10.1056/NEJMoa071359 · 54.42 Impact Factor