A Randomized, Controlled Trial for Homocysteine

描述（改编自应用程序） 这项多中心、随机、双盲对照的临床试验已被 旨在确定是否总同型半胱氨酸（tHcy）降低治疗， 一种标准的多种维生素，加上高剂量的叶酸， 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，降低了复发率和死亡率。 新发心血管疾病结果（即，非致死性和 致命性动脉炎结局，包括冠心病、脑血管疾病和 外周血管疾病事件=主要结局），在临床稳定 轻度至中度tHcy水平升高的肾移植受者。 基本合格标准是年龄35至75岁，肾功能正常， 同种异体移植超过6个月，血清肌酐为基础的肌酐 清除率大于30 mL/min，且筛选随机tHcy水平大于 高于12 μ M/L。患者将根据以下情况进行分层： 临床CVD，并随机分配到标准复合维生素治疗组 含有叶酸、维生素B6和维生素B12的高剂量组合， 或不含这三种微量营养素的相同复合维生素。随机 患者还将进行甲硫氨酸负荷试验。所有患者将接受 降低传统CVD危险因素的标准临床管理。的 研究设计在2年内招募4000例患者（每组2000例） 83%的把握度检测25%的治疗效果。继续随访 直至发生新发或复发性非致死性CVD，或死亡，或 四年。数据分析将在原始数据的基础上进行 随机化（意向治疗），使用对数秩检验差异 无终点生存曲线。 在当前的时代，谷物面粉强化了生理量的 叶酸，RTR包括特别适合测试的患者群体， 降低tHcy治疗将减少CVD结果的合理假设， 考虑到：a）他们轻度高同型半胱氨酸血症的持续过度患病率 与之相反，例如， 具有正常肾功能的患者; B）经证实的 B族维生素治疗方案具有超生理量的叶酸 成功地使RTRs中的tHcy水平“正常化”。此外，总体而言， RTR群体中的“条件”（即，轻度至中度肾损害 可通过超生理剂量B族维生素使其正常化的高同型半胱氨酸血症 补充剂和高CVD事件发生率）代表了较大的 慢性肾功能不全患者人群，尚未 透析依赖性。因此，拟议审判的结果非常 可能会推广到更大规模的患者人群， 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.