Common use of Study Objectives Clause in Contracts

Study Objectives. The primary endpoint of this sub-study was the change in CRP between 24 months and baseline. The relationship between CRP and MS score was a secondary endpoint. Patients returned to the study site after 12 hours fast at 3, 6, 12, 18 and 24 months when blinded lipid and safety measurements (creatinin kinase, ALT) were performed. CRP was measured at baseline and at 24 months. Lipid and safety measurements were performed at the Department of Clinical Chemistry and Hematology of the HAGA Hospital, according to ISO 15189 standard procedures. Blood samples were collected from the subjects after a 12 hour fast. EDTA tubes were used for the determination of HbA1c. Liver enzymes and lipids were measured in serum. A urine sample was collected for the determination of the albumin-to-creatinin ratio. The high sensitive CRP assay was performed in the Leiden University Medical Center with the Tina Quant C-reactive protein (latex) high sensitive assay from Roche using particle en- hanced immunoturbidimetry on a Roche Module P(Basel, Switzerland). The lower detection limit (analytical sensitivity) is 0.03 mg/L and the functional sensitivity 0.11 mg/L. The intra- assay CV is 1.34% at 0.55 mg/L and the inter-assay CV is 5.70% at 0.52 mg/L. All CRP assays were performed after completion of the study. The primary treatment comparison was between placebo and statin therapy in patients com- pleting the study, as on-treatment analysis. CRP values more than 15 mg/L were excluded. As CRP values were not normally distributed, logarithmic transformations were used. Changes within each treatment group were analyzed using Student’s paired t-test. Comparisons of the effects between the treatment groups were performed using Student’s independent samples t-test. Analysis of the baseline data was performed in all randomized patients. Step- wise regression techniques were used to investigate the effect of baseline characteristics on baseline CRP and on changes in CRP. ANOVA was used to investigate the relation between the MS score (1 point for every criterion (waist, triglycerides, HDL cholesterol and blood pres- sure) according to the NCEP/ATPIII criteria25) and baseline CRP. In addition, the effect of statin treatment on CRP was analyzed in a high-risk patient group with 3 or 4 additional MS criteria on top of their diabetes and LDL cholesterol levels > 2.6 mmol/L26. To test the equivalence of cerivastatin 0.4 mg and simvastatin 20 mg, LDL levels before and after the switch to simvas- tatin were compared using Student’s paired t-test. Correlation between changes in CRP and changes in other parameters were evaluated with Pearson’s correlation coefficients. Analyses were performed using SPSS 11.0 for Windows software. All analyses were 2-sided, with a level of significance of α = 0.05.