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Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research



Protocol

Trial governance

NAVIGATOR is managed by Novartis Pharmaceuticals.  Academic oversight is provided by Executive and Steering Committees, co-chaired by Professor Rury Holman (diabetologist) and Professor Robert Califf (cardiologist).  An independent Data Monitoring Committee (DMC) provides oversight of the safety of enrolled participants

Sponsor

Novartis Pharmaceuticals

Study title

A multinational, randomized, double-blind, placebo-controlled, forced-titration, 2.2 factorial design study of the efficacy and safety of long term administration of nateglinide and valsartan in the prevention of diabetes and cardiovascular outcomes in subjects with impaired glucose tolerance (IGT)

Study Drug

Participants in NAVIGATOR are randomized in a 2x2 placebo-controlled fashion to

and

Patient Population

Eligible participants are aged 50 years or older with

Scope

NAVIGATOR enrolled 9518 participants between January 2002 and January 2004 in 39 countries.

Study design

Valsartan
comparison
Nateglinide
comparison
Valsartan
Nateglinide
Placebo
Nateglinide
Valsartan
Placebo
Placebo
Placebo

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 cardiovascular (CV) events in subjects with impaired glucose tolerance (IGT) who have established CVD or are at high risk for CVD.  Patients were allocated randomly in a 1:1:1:1 ratio to receive 1 of 4 possible treatment combinations (see Figure).  In addition, subjects receive clinic-based and telephone-based lifestyle intervention aimed at reducing body weight and dietary fat intake and increasing physical activity.
After an initial drug-titration phase, participants are seen every 6 months for the remainder of the trial, which has an expected median duration of 8 years. Fasting plasma glucose concentrations (FPGs) are measured every 6 months for the first 3 years and annually thereafter. An oral glucose tolerance test (OGTT) is performed annually to ascertain PD. All putative PD and CV end points are adjudicated by independent committees.

Primary Objective

To compare the impact of long-term use of nateglinide and valsartan on three co-primary endpoints:

These events are reported by investigators and reviewed by an independent end point adjudication committee.

Study Timelines

NAVIGATOR completed enrollment between January 2002 and January 2004.  Study follow up is ongoing and is anticipated to be completed in late 2009.  Study results are anticipated in 2010.