title: Design and rationale of a real-life study to compare treatment strategies for cardiovascular risk factors: the CRUCIAL study.
abstract: The CRUCIAL trial was designed to compare the relative reduction in calculated Framingham coronary heart disease risk when a multiple risk factor intervention strategy, based on single-pill amlodipine besylate/atorvastatin calcium, was compared with a usual-care strategy. Eligible patients had treated or untreated hypertension, >or=3 additional cardiovascular risk factors, and baseline total cholesterol<or=6.5 mmol/L, but no coronary heart disease. The CRUCIAL trial was a 12-month, international, multicenter, prospective, stratified, cluster-randomized, parallel-design, open-label trial conducted in 20 countries in Asia, the Middle East, Europe, and Latin America. We anticipate the results of this study will be available in mid to late 2010. In this article we report the rationale for and design of the CRUCIAL trial and discuss how the challenges in the design and conduct of this cluster-randomized trial were addressed. The cluster-randomized trial design, with the investigator as the unit of randomization, was chosen to minimize contamination between the trial arms. The intent of the study was to compare the new therapeutic strategy with customary treatment practices, so no recommendation was made regarding the choice of antihypertensive or lipid-lowering drugs in the usual-care arm. It was considered that if the investigator managed both arms of the trial it would be difficult to prevent crossover of treatment strategies. Patients were enrolled in the study before the investigators were randomized to avoid selection bias. Investigators were randomized in a 1:1 ratio within each country to explicitly balance the treatment arms with respect to potential confounding factors. The cluster effect was taken into account in the sample size calculation. The findings from the CRUCIAL trial have the potential to inform current thinking on how to effectively reduce the cardiovascular risk of patients with hypertension and additional risk factors but only modestly elevated total cholesterol.
authors.affiliation: Servicio de Cardiología, Hospital Clínico San Carlos, Madrid, 28040, Spain. zamorano@secardiologia.es
authors.forename: José
authors.initials: J
authors.lastname: Zamorano
authors.forename: Serap
authors.initials: S
authors.lastname: Erdine
authors.forename: Abel Pavia
authors.initials: AP
authors.lastname: Lopez
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Ayman
authors.initials: A
authors.lastname: Al Khadra
authors.forename: Mogens
authors.initials: M
authors.lastname: Westergaard
authors.forename: Santosh
authors.initials: S
authors.lastname: Sutradhar
authors.forename: Carla
authors.initials: C
authors.lastname: Yunis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D016000:Cluster Analysis; D004338:Drug Combinations; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000517:prevention & control; D006973:Hypertension / Q000188:drug therapy / Q000517:prevention & control; D038622:Internationality; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D006538:Heptanoic Acids; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin