Pragmatic Randomized Trial of Calcitriol in Patients with Chronic Kidney Disease

描述（由申请人提供）：慢性肾病（CKD）很常见，并且与大量的发病率和死亡率相关，这主要是由于心血管疾病的发病率增加所致。骨化三醇（1,25-二羟基维生素 D3，活性维生素 D 激素）是一种特别有前景的治疗方法，可降低 CKD 的心血管发病率和死亡率。肾脏是骨化三醇产生的主要场所，即使服用标准维生素 D 补充剂，CKD 患者的循环骨化三醇浓度也会急剧下降。骨化三醇的刺激性心脏保护作用已在动物实验模型中得到证实，并且对 CKD 患者的观察性研究一致证明了骨化三醇的使用与死亡率降低之间的关联。然而，尚无临床试验测试骨化三醇对临床结果的影响。拟议研究的目的是 在一项随机临床试验中确定使用骨化三醇（每天口服 0.25 微克）是否可以降低 CKD 患者（估计肾小球滤过率 20-59 mL/min/1.73m2）心血管疾病事件的风险。在我们研究的 UH2 阶段，我们的目标是证明将精心设计的骨化三醇临床试验整合到大型综合医疗保健系统 Group Health Cooperative 的临床护理基础设施中的可行性。在我们研究的 UH3 阶段，该研究的目的是在 4,370 名患有 CKD 的健康人群中测试骨化三醇加常规护理与单独常规护理相比对临床相关心血管结局（心肌梗死、急性冠状动脉综合征、中风、住院心力衰竭或心血管死亡的主要复合结局）发生的影响。次要结局将包括主要复合结局的组成部分以及 CKD 进展为终末期肾病。我们组建了一个由 Group Health 和华盛顿大学的多学科合作者团队来开发和开展这项务实的临床试验。该研究将通过应用最低资格标准并利用广泛的电子资源来识别参与者、提供和监测研究干预以及确定研究结果，从而最大限度地提高效率、经济性和外部有效性。个体层面的随机化、促进保留和坚持的标准化方案以及对研究结果的严格确定将增强内部有效性。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is common and is associated with substantial morbidity and mortality, which is largely due to an increased incidence of cardiovascular diseases. Calcitriol (1,25-dihydroxyvitamin D3, the active vitamin D hormone) is a particularly promising treatment to reduce cardiovascular morbidity and mortality in CKD. The kidneys are the major site of calcitriol production, and circulating calcitriol concentrations fall dramatically in CKD, even when standard vitamin D supplements are administered. Provocative cardioprotective actions of calcitriol have been demonstrated in animal-experimental models, and observational studies of people with CKD consistently demonstrate associations of calcitriol use with reduced mortality. However, no clinical trial has tested the effects of calcitriol on clinical outcomes. The objective of the proposed research is to determine, in a randomized clinical trial, whether calcitriol use (0.25 mcg by mouth daily) reduces the risk of cardiovascular disease events among people with CKD (estimated glomerular filtration rate 20-59 mL/min/1.73m2). During the UH2 phase of our study, we aim to demonstrate the feasibility of integrating a well-designed pragmatic clinical trial of calcitriol ito the clinical care infrastructure of Group Health Cooperative, a large integrated health care system. During the UH3 phase of our study, the study aim is to test the effect of calcitriol plus usual care, compared with usual care alone, on the occurrence of clinically relevant cardiovascular outcomes (primary composite outcome of myocardial infarction, acute coronary syndrome, stroke, hospitalized heart failure, or cardiovascular death) among 4,370 Group Health patients with CKD. Secondary outcomes will include components of the primary composite outcome and progression of CKD to end stage renal disease. We have assembled a multidisciplinary team of collaborators from Group Health and the University of Washington to develop and conduct this pragmatic clinical trial. The study will maximize efficiency, economy, and external validity by applying minimal eligibility criteria and by utilizing an extensive array f electronic resources to identify participants, deliver and monitor the study intervention, and ascertain study outcomes. Individual-level randomization, standardized protocols to promote retention and adherence, and rigorous ascertainment of study outcomes will enhance internal validity.