A Randomized, Controlled Trial for Homocysteine

说明(改编自应用程序) 这项多中心、随机、双盲对照临床试验 旨在确定通过以下方法降低总同型半胱氨酸(THcy) 一种标准的复合维生素，添加了高剂量的叶酸组合， 维生素B12和维生素B6，与标准复合维生素治疗相比 缺乏这三种B族维生素，可降低复发率和死亡率 新的心血管疾病结果(即，非致命性和非致命性 致命的动脉硬化结果，包括冠心病、脑血管和 外周血管疾病事件=主要结果)，临床稳定 THcy水平轻度至中度升高的肾移植受者。 基本的资格标准是年龄在35岁到75岁之间，肾脏功能正常 同种异体移植6个月以上，以血肌酐为基础 清除量大于30毫升/分钟，筛查随机tHcy水平较大 超过12微米/升的患者将根据有无 临床脑血管病，随机分配标准复合维生素治疗 含有高剂量的叶酸、维生素B6和维生素B12， 或者不含这三种微量营养素的完全相同的复合维生素。随机化 患者还将接受蛋氨酸负荷测试。所有患者都将收到 降低传统心血管疾病危险因素的标准临床管理。这个 这项研究计划在两年内招募4000名患者(每组2000名) 治疗期间以83%的功率检测25%的疗效。后续行动仍在继续 直到发生新发或复发的非致命性脑血管病，或死亡，或最高 四年的时间。数据分析将在原始的基础上进行 随机化(意向处理)使用差异的对数等级检验 无终点生存曲线。 在当前的谷物面粉时代，添加了生理剂量的 叶酸，RTRS构成了一个特别适合测试的患者群体 降低tHcy治疗将减少心血管疾病预后的假设是站得住脚的， 给予：a)轻度高同型半胱氨酸血症的持续超常流行 相比之下，防御工事后，例如，对于冠心病 肾功能正常的患者；b)证明有能力 以超生理剂量叶酸为特征的B-维生素治疗方案 成功地使RTRS中的tHcy水平“正常化”。此外，总体来说， RTR人群的“状况”(即肾功能损害，轻至中度 高同型半胱氨酸血症可通过超生理剂量维生素B恢复正常 补充剂和高心血管事件发生率)代表较大的 慢性肾功能不全患者的人口，他们还没有 依赖透析。因此，拟议的试验结果非常 很可能推广到更大规模的患者群体 肾功能不全进展为终末期肾病。

DESCRIPTION (Adapted from the application) This multicenter, randomized, double-blind controlled clinical trial has been designed to determine whether total homocysteine (tHcy)-lowering treatment with a standard multivitamin augmented by a high dose combination of folic acid, vitamin B12, and vitamin B6, versus treatment with a standard multivitamin devoid of these three B-vitamins, reduces the pooled rate of recurrent and de novo cardiovascular disease outcomes (i.e., pooled occurrence of non-fatal and fatal arteriosclerotic outcomes, including coronary heart, cerebrovascular, and peripheral vascular disease events= primary outcome), among clinically stable renal transplant recipients who have mild to moderately elevated tHcy levels. The basic eligibility criteria are age 35 to 75 years old, functioning renal allograft for greater than six-months with serum creatinine based creatinine clearance greater than 30 mL/min, and a screening random tHcy level greater than12 uM/L. Patients will be stratified based on the presence/absence of clinical CVD, and randomly assigned to treatment with a standard multivitamin containing a high dose combination of folic acid, vitamin B6, and vitamin B12, or an identical multivitamin devoid of these three micronutrients. Randomized patients will also undergo a methionine loading test. All patients will receive standard clinical management for traditional CVD risk factor reduction. The study is designed to recruit 4000 patients (2000 in each group) over a two-year period for 83% power to detect a 25% treatment effect. Follow-up continues until occurrence of de novo or recurrent non-fatal CVD, or death, or a maximum of four-years. Data analysis will be performed on the basis of original randomization (intention to treat) using the log-rank test of difference in survival-without-endpoint curves. In the current era of cereal grain flour fortified with physiologic amounts of folic acid, RTRs comprise a patient population particularly well-suited to test the tenable hypothesis that tHcy-lowering treatment will reduce CVD outcomes, given: a) their persistent excess prevalence of mild hyperhomocysteinemia post-fortification, in contrast, for example, to coronary heart disease patients with normal renal function; b) the demonstrated capability of B-vitamin treatment regimens featuring supraphysiologic amounts of folic acid to successfully "normalize" tHcy levels in RTRs. Furthermore, overall "conditions" in the RTR population (i.e., renal impairment, mild to moderate hyperhomocysteinemia which can be normalized by supraphysiologic dose B-vitamin supplements, and high CVD event rates) are representative of the larger population of patients with chronic renal insufficiency, who are not yet dialysis-dependent. Accordingly, findings from the proposed trial are very likely to be generalizable to the much more sizable population of patients with renal insufficiency progressing to end-stage renal disease.