STUDY OF LONG-TERM ADMINISTRATION OF NATEGLINIDE AND VALSARTAN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究是一项多国、随机、双盲、安慰剂对照、强制滴定的2 × 2因子设计研究，目的是研究长期服用那格列奈和缬沙坦在糖耐量受损（IGT）受试者中预防糖尿病和心血管结局的有效性和安全性。此外，我们将进行一项亚研究，以确定内皮功能和身体成分是否能预测IGT患者糖尿病和心血管事件的发展。来自所有6个新奥尔良领航员研究站点的患者将被邀请参加本子研究（也可以在其他愿意/能够执行这些程序的站点合并为子研究）。在OGTT筛查中糖耐量受损且大于或等于1个心血管危险因素（RF）或大于或等于1个心血管疾病（CVD）的男性和女性受试者均有资格参加。每个治疗组将随机抽取大约1875名受试者。在核心阶段结束时，将对进展到糖尿病终点的时间进行数据分析，同时将以盲法方式继续进行试验。如果一种或两种药物的统计显著性效果，将考虑提交注册档案。如果任何药物没有达到统计学意义，试验将继续进行，心血管发病率/死亡率终点的分析将是探索性的。来自约40个国家600-800个中心的约7500名受试者将被随机化。资格筛查将在治疗开始前1个月进行，并需要进行口服葡萄糖耐量试验（OGTT）以确认资格。在收到适当的基线数据和心血管疾病状态后，符合条件的受试者将被随机分配到四个治疗组中的一个（比例1:1:1:1），即那格列奈60mg ac，缬沙坦160mg od，那格列奈60mg ac和缬沙坦160mg od，那格列奈60mg ac和缬沙坦l60mg od，或安慰剂，使用计算机交互式语音应答系统（IVRS）。预计需要大约18个月的学习收益。研究随访的持续时间是固定的，从患者最后一次就诊（LPFV）起进展到糖尿病终点至少3年。这个持续时间也定义了核心阶段的持续时间。对于心血管终点，需要1000名有事件的患者。预计FPFV术后总随访时间为5年零9个月。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is a multinational, randomized, double-blind, placebo-controlled, forced-titration 2 x 2 factorial design study of the efficacy and safety of long term administration of nateglinide and valsartan in the prevention of diabetws and cardiovascular outcomes in subjects with impared glucose tolerance (IGT). In addition, we will conduct a substudy to determine whether endothelial function and body composition predict the development of diabetes and cv events in patients with IGT. Patients from all 6 New Orleans Navigator study sites will be invited to participate in this sub study (which may also be incorporated as a substudy at other sites willing/able to carry out these procedures). Male and female subjects with impaired glucose tolerance on OGTT screening and greater than or equal to 1 cardiovascular risk factors (s) (RF) or greater than or equal to 1 cardiovascular disease (CVD) are eligible to participate. Approximately 1875 subjects will be randomized per treatment group. At the end of the core phase, the data will be analyzed for the time to progression to diabetes endpoint while the trial will continue in a blinded fashion. In case of a statistically significant effect of one or both drugs, submission of a registration dossier will be considered. If no statistical significance is reached by any of the drugs the trial will continue and the analysis of the cardiovascular morbidity/mortality endpoint will be exploratory. Approximately 7500 subjects from 600-800 centers in approximately 40 countries are to be randomized. Screening for eligibility will take place 1 month prior to treatment start and requires an oral glucose tolerance test (OGTT) to confirm eligibility. After receipt of the appropriate baseline data and cardiovascular disease status, eligible subjects will be randomly assigned to one of the four treatment groups (ratio 1:1:1:1), i.e. nateglinide 60 mg ac, valsartan 160 mg od, the combination of nateglinide 60 mg ac and valsartan 160 mg od, the combination of nateglinide 60 mg ac and valsartan l60 mg od, or placebo, using a computerized interactive voice response system (IVRS). Study accrual is expected to require approximately 18 months. The duration of study follow-up is fixed for the progression to diabetes endpoint at a minimum of 3 years from last-patient first-visit (LPFV). This duration also defines the duration of the core phase. For the cardiovascular endpoint, 1000 patients with an event are required. A total duration of follow-up of 5 years and 9 months after FPFV is anticipated.