Design of the Wegener's Granulomatosis Etanercept Trial (WGET).

Wegener's granulomatosis (WG) is among the most common forms of systemic vasculitis. WG is associated with a high mortality in patients who do not receive appropriate treatment. Substantial morbidity results from standard disease therapies, however, and there is a high risk of relapse (exceeding 50%) following the taper of standard medications. The greatest challenges in the management of WG are the maintenance of disease remission and the avoidance of treatment-related morbidity and mortality. The Wegener's Granulomatosis Etanercept Trial (WGET) is a randomized, double-masked, placebo-controlled trial designed to test the ability of etanercept, a soluble inhibitor of tumor necrosis factor, to maintain disease remission when used with conventional treatments. Eight WGET clinical centers plan to enroll 180 patients over a 30-month period. The randomization is stratified by clinic and by disease severity. Patients are assigned randomly to receive etanercept or placebo in an allocation ratio of 1:1. They continue to receive standard WG therapies in regimens defined by the protocol. Upon the achievement of remission, these standard medications are tapered according to protocol guidelines. The primary outcome is sustained remission. Secondary and tertiary outcomes include a number of disease- and treatment-related measures. The trial will have a common closing date 12 months after the last patient is randomized. The primary analysis will be performed on an intention-to-treat basis. WGET is the first randomized trial in WG in the United States and the first multicenter trial of a biologic agent in WG. One year after the start of enrollment, 106 patients have been randomized. The objectives of this paper are: (1) to describe the design of the WGET; (2) to discuss issues related to the trial's development; and (3) to review some aspects of its conduct to date.