Search

In the United States, glucosamine is marketed as a dietary supplement therefore subject to less stringent manufacturing, labeling and marketing regulations than pharmaceuticals. The glucosamine product selected for the NIH-sponsored Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) was required to satisfy Investigational New Drug (IND) application (and therefore pharmaceutical manufacturing requirements). This review describes the procedure that was developed by the authors to identify a high-quality glucosamine product for GAIT and to clarify confusing product information and nomenclature. Proprietary glucosamine products and bulk glucosamine powders of various salt forms were evaluated. Both the published literature and information provided by suppliers of bulk glucosamine powders were evaluated. No proprietary glucosamine product was selected due to manufacturing practices that did not meet the pharmaceutical standards mandated by GAIT; i.e., no practices that control and document the quality issues of product purity and content variability. At the time this study was initiated dietary supplements were not required to meet these standards. Other problems identified with proprietary products included the presence of other dietary supplements and/or trace elements and the inability of a manufacturer to provide the appropriate quality of product within the time constraints of the study. A bulk powder of glucosamine hydrochloride was identified and capsules were manufactured for the trial in compliance with pharmaceutical Good Manufacturing Practices. [ABSTRACT FROM AUTHOR]

Objectives: This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. Background: Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. Methods: All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. Results: The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked ≥150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 ± 0.13 kg/m2 to 29.3 ± 0.23 kg/m2 (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 ± 0.49 mm Hg to 123 ± 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 ± 0.83 mg/dl to 72 ± 0.88 mg/dl. Conclusions: Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) [Copyright &y& Elsevier]

Major improvements in medical therapy and percutaneous coronary intervention for coronary artery disease (CAD) have emerged during the previous 2 decades, but no randomized trial in patients with stable CAD has been powered to compare these 2 strategies for the hard clinical end points of death or myocardial infarction (MI), and previous studies have not evaluated the effect of coronary stents and intensive medical therapy on cardiac events during long-term follow-up. Between 1999 and 2004, 2,287 patients with documented myocardial ischemia and angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a principal hypothesis that a strategy of percutaneous coronary intervention plus intensive, guideline-driven medical therapy would be superior to a strategy of intensive medical therapy alone. The primary end point was a composite of all-cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median 5) follow-up. Baseline characteristics were a mean age of 62 ± 5 years, 85% men, and 86% Caucasian. Mean duration of angina before randomization was 26 months (average 10 episodes/week), and 29% of patients were smokers, 67% had hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27% had previous revascularization, and 69% had multivessel CAD. Approximately 55% of patients met established criteria for the metabolic syndrome. In conclusion, baseline characteristics of the COURAGE trial study population indicate a highly symptomatic group of patients with CAD who have a significant duration and frequency of antecedent angina pectoris and a high prevalence of cardiac risk factors. [Copyright &y& Elsevier]