Rationale for use of an exercise end point and design for the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial.
BACKGROUND: Exercise intolerance is a primary characteristic of chronic congestive heart failure. Exercise testing is therefore widely used to evaluate the degree of functional impairment, prognosis of underlying cardiac disease, and response to treatment. Historically, studies that used exercise tolerance as an end point to evaluate the efficacy of pharmacologic interventions have been confounded by methodologic differences involving protocols, exercise end points, absence or misuse of gas exchange data, and study design. METHODS: The purpose of this study was to outline the methodology and rationale of a unique cardiopulmonary exercise trial. The design was based on prior experience from evaluation of ACE inhibitors and other interventions. The ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial is a multicenter, double-blind, placebo-controlled, randomized trial investigating the effects of a vasopressin antagonist, conivaptan, on functional capacity in patients with heart failure. RESULTS: The primary end point is change in the exercise time to reach 70% of peak oxygen consumption during an incremental exercise test. Secondary end points include changes in peak oxygen consumption and other exercise parameters as well as quality-of-life indicators. The study incorporates several unique features to lessen potential methodological errors of exercise testing in heart failure, including use of a core laboratory to evaluate exercise tests, a computer program to determine the exercise end points, and validation of each site before patient enrollment. CONCLUSIONS: The results of this study will have value not only for the further use of vasopressin antagonists for heart failure therapy but also for the use of exercise testing and gas exchange determination for the evaluation of new drug therapies.
Russell, SD; Selaru, P; Pyne, DA; Ghazzi, MM; Massey, KD; Pressler, M; Serikoff, A; Coats, AJS
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