Received December 22, 2006
Accepted on June 25, 2007

ORIGINAL ARTICLES

Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): Rationale and Design Overview

Glenn M. Chertow ^*, Lara B. Pupim , Geoffrey A. Block , Ricardo Correa-Rotter , Tilman B. Drueke ^||, Jürgen Floege ^¶, William G. Goodman ^**, Gerard M. London , Kenneth W. Mahaffey , Sharon M. Moe , David C. Wheeler ^||, Moetaz Albizem , Kurt Olson , Preston Klassen , and Patrick Parfrey ^¶¶1

*Departments of Medicine and Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Amgen Inc., Thousand Oaks, California; Denver Nephrologists PC, Denver, Colorado; Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; ||INSERM Unit 845 and Nephrology, Hopital Necker, Paris, France; ¶Department of Nephrology, University Hospital, Rheinisch Westfälische Technische Hochschule University of Aachen, Aachen, Germany; **Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California; Service de Néphrologie Hôpital Manhès, Fleury-Mérogis, France; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Indiana University School of Medicine and Roudebush VAMC, Indianapolis, Indiana; || ||Center for Nephrology, Royal Free and University College Medical School, London, United Kingdom; and ¶¶Health Sciences Centre, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada

¹ To whom correspondence should be addressed. E-mail: pparfrey{at}mun.ca.

	Abstract

Background and Objectives: The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events. However, no prospective trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes.

Design, Setting, Participants, & Measurements: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global, phase 3, double-blind, randomized, placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism. Approximately 3800 patients from 22 countries will be randomly assigned to cinacalcet or placebo. Flexible use of traditional therapies will be permitted. The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event (myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular disease, including lower extremity revascularization and nontraumatic amputation).

Results: The study will be event driven (terminated at 1882 events) with an anticipated duration of approximately 4 yr.

Conclusions: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients.