STUDY OF LONG-TERM ADMINISTRATION OF NATEGLINIDE AND VALSARTAN

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究是一项多国、随机、双盲、安慰剂对照、强制滴定2 x 2析因设计研究，旨在评价长期服用那格列奈和缬沙坦预防糖耐量异常（IGT）受试者糖尿病和心血管结局的有效性和安全性。此外，我们将进行一项子研究，以确定内皮功能和身体成分是否可预测IGT患者糖尿病和心血管事件的发生。将邀请来自所有6家新奥尔良Navigator研究中心的患者参加此项子研究（也可能在愿意/能够进行这些程序的其他研究中心纳入为子研究）。 OGTT筛选时糖耐量受损且存在1种以上心血管风险因素（RF）或1种以上心血管疾病（CVD）的男性和女性受试者有资格参加研究。每个治疗组将随机分配约1875例受试者。 在核心阶段结束时，将分析数据至进展至糖尿病终点的时间，同时试验将以设盲方式继续进行。如果一种或两种药物的作用具有统计学显著性，将考虑提交注册档案。如果任何药物均未达到统计学显著性，则试验将继续进行，心血管发病率/死亡率终点的分析将是探索性的。 来自约40个国家的600-800家中心的约7500例受试者将接受随机化。合格性筛选将在治疗开始前1个月进行，需要口服葡萄糖耐量试验（OGTT）确认合格性。在收到适当的基线数据和心血管疾病状态后，合格受试者将使用计算机交互式语音应答系统（IVRS）随机分配至4个治疗组之一（比例1：1：1：1），即那格列奈60 mg ac、缬沙坦160 mg od、那格列奈60 mg ac和缬沙坦160 mg od联合治疗、那格列奈60 mg ac和缬沙坦160 mg od联合治疗或安慰剂。 研究累积预计需要约18个月。对于进展至糖尿病终点，研究随访的持续时间固定为自末例患者首次访视（LPFV）起至少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例发生事件的患者。预计FPFV后的总随访时间为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.