Candesartan antihypertensive survival evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: Rationale, design, and methods
Candesartan antihypertensive survival evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: Rationale, design, and methods
复制标题
DOI：
10.1291/hypres.26.979
复制
发表时间：
2003-12-01
影响因子：
5.4
通讯作者：
Fukiyama, K
中科院分区：
文献类型：
--
作者：
Fukui, T;Rahman, M;Fukiyama, K
高血压仍然是世界上主要的公共卫生问题。为了解决这个问题，在过去的半个世纪，已经开发了许多抗高血压药物，并证明其在控制血压方面有效。近几十年来，抗高血压药物已被证明具有心血管益处，而不仅仅是降低血压，重点已经转移到澄清这些作用。血管紧张素II受体拮抗剂和钙通道阻滞剂是日本最广泛使用的抗高血压药物。然而，这两类药物尚未就其治疗心血管事件的疗效进行比较。本文所述的坎地沙坦抗高血压生存评价在日本（CASE-J）试验是一项前瞻性、多中心、随机、开放标签、活性对照、在接受血管紧张素II受体拮抗剂（坎地沙坦酯）或第三代钙通道阻滞剂（阿苯磺酸）治疗的高危高血压患者中进行反应依赖性剂量滴定和终点盲态评估的双臂平行组比较。本研究的合格标准为：1）年龄在20 - 85岁之间; 2）在门诊连续两次测量收缩压（SBP）≥ 140 mmHg（70岁以下）或≥ 160 mmHg（70岁以上）或舒张压（DBP）≥ 90 mmHg;和3）至少一种以下心血管事件的高风险因素：a）连续两次访视时SBP ≥ 180 mmHg或DBP ≥ 110 mmHg，B）2型糖尿病（空腹血糖大于或等于126 mg/dl，偶然血糖大于或等于200 mg/dl，HbA 1c大于或等于6.5%，2、75 g口服葡萄糖耐量试验（OGTT）时血糖大于或等于200 mg/dl，或目前用低血糖治疗），c）直到筛选前6个月有脑出血、脑梗塞或短暂性脑缺血发作史，d）超声心动图或ECG显示左心室肥大，心绞痛，或筛选前6个月的心肌梗塞史，e）蛋白尿或血清肌酐大于或等于1.3mg/dl，和f）动脉阻塞的症状。血压控制的治疗目标设定为：60岁以下患者SBP < 130 mmHg且DBP < 85 mmHg，60岁以上患者SBP < 140 mmHg且DBP < 90 mmHg，70岁以上患者SBP < 150 mmHg且DBP < 90 mmHg，80岁以上患者SBP < 160 mmHg且DBP < 90 mmHg。根据双侧α水平0.05和90%把握度，共需要3，200例患者，平均分配至两个治疗组。CASE-J也是第一个使用新开发的自动条形码数据采集/分配、预订和试用编码、数据管理（TM）系统进行数据收集和管理的研究。患者入组开始于2001年9月，结束于2002年12月。将每6个月收集一次随访数据，直至2005年12月。CASE-J试验将提供重要证据，证明坎地沙坦酯和苯磺酸氨氯地平对日本人心血管发病率和死亡率的比较有效性。此外，ABCD（TM）系统的使用预计将有助于为大规模临床试验开发更有效的数据管理系统。
Hypertension continues to be a major public health issue in the world. To combat this problem, many antihypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, anti hypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used anti hypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Anti hypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) greater than or equal to 140 mmHg in those below 70 years of age or greater than or equal to 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) greater than or equal to 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP greater than or equal to 180 mmHg or DBP greater than or equal to 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose greater than or equal to 126 mg/dl, casual blood glucose greater than or equal to 200 mg/dl, HbA1c greater than or equal to 6.5%, 2,h blood glucose on 75 g oral glucose tolerance test (OGTT) greater than or equal to 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine greater than or equal to 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management(TM) (ABCD(TM)) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD(TM) system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.