Trial DesignPrevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: Rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial
Section snippets
Overview of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial
The NAVIGATOR trial is a multinational, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial investigating whether treatment with nateglinide or valsartan will reduce progression to diabetes (PD) and new CV events in subjects with impaired glucose tolerance (IGT) who have established CVD or are at high risk for CVD. A total of 9,306 of the 9,518 patients enrolled (Table I) and randomized were included in the final analysis. Patients were allocated randomly in a 1:1:1:1 ratio to
Key issues in trial design
Numerous recent studies in CVD and diabetes underscore the complexity and risk of using biochemical measures to predict which therapies are preferable for treating long-term diseases.35, 36, 37 Rather than simply attempting to determine whether nateglinide and valsartan reduce diabetes incidence or delay PD, NAVIGATOR directly addresses the effect of interventions on the CV mortality and morbidity that dominate clinical decision-making, thus markedly increasing the sample size required to
Conclusion
The enormous burden of diabetes worldwide is leading to an increase in prevalence of CVD.3 The resulting excess morbidity, mortality, and costs will overburden many health care delivery systems unless action is taken. The NAVIGATOR trial is unique in addressing both the relationship between the metabolic abnormalities in IGT and diabetes and the later development of CVD by testing 2 distinct but unified hypotheses. The nateglinide treatment arm tests whether reducing postprandial hyperglycemia
References (49)
- et al.
Diabetes and ischemic heart disease
Am Heart J
(1999) - et al.
Determining the most appropriate components for a composite clinical trial outcome
Am Heart J
(2008) - et al.
Effect of angiotensin-converting–enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial
Lancet
(1999) - et al.
Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial
Lancet
(2004) - et al.
Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial
Lancet
(2005) - et al.
Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial
Lancet
(2004) - et al.
Global burden of diabetes, 1995-2025. Prevalence, numerical estimates, and projections
Diabetes Care
(1998) - et al.
Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults
Diabetes Care
(1998) - et al.
Global and societal implications of the diabetes epidemic
Nature
(2001) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus
N Engl J Med
(1993)
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
N Engl J Med
Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial
JAMA
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance
N Engl J Med
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
N Engl J Med
Report of the expert committee on the diagnosis and classification of diabetes mellitus
Diabetes Care
Definition, diagnosis, and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus
The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus
J Clin Invest
Aspects of the pathogenesis of type 2 diabetes
Endocrine Rev
Nateglinide prescribing information
Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166)
Diabetes Care
Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the studies of left ventricular dysfunction (SOLVD)
Circulation
Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients
N Engl J Med
Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic
JAMA
Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD)
Circulation
Cited by (86)
Postprandial effect of fresh and processed orange juice on the glucose metabolism, antioxidant activity and prospective food intake
2019, Journal of Functional FoodsHeart Failure: Epidemiology, Pathophysiology, and Management of Heart Failure in Diabetes Mellitus
2018, Endocrinology and Metabolism Clinics of North AmericaUpdated risk factors should be used to predict development of diabetes
2017, Journal of Diabetes and its ComplicationsCitation Excerpt :Comparatively little is known about the impact of change in common risk factors over time on risk prediction.8 Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study (ClinicalTrials.gov NCT00097786), we investigated the incremental benefit to diabetes risk prediction of updating risk factors after 1 year of follow up.9–11 The NAVIGATOR study design and results have been previously published.9–11
Venous thromboembolism and cardiovascular risk: Results from the NAVIGATOR trial
2015, American Journal of Medicine
This study is funded by Novartis Pharma AG, Basel, Switzerland.
- *
See Appendix A for executive committee members. As chair of the trial, Dr Califf takes responsibility for the content of this article.