Pragmatic Randomized Trial of Calcitriol in Patients with Chronic Kidney Disease

描述（由申请人提供）：慢性肾脏疾病（CKD）是一种常见的疾病，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。骨化三醇（1,25-二羟基维生素D3，活性维生素D激素）是一种特别有前途的治疗方法，可以降低CKD的心血管发病率和死亡率。肾脏是骨化三醇产生的主要部位，CKD患者循环骨化三醇浓度急剧下降，即使服用了标准的维生素D补充剂。骨化三醇的心脏保护作用已在动物实验模型中得到证实，对CKD患者的观察性研究一致表明，骨化三醇的使用与降低死亡率有关。然而，没有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

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.