Lessons learned from EVOLVE for planning of future randomized trials in patients on dialysis

Patrick S. Parfrey, Geoffrey A. Block, Ricardo Correa-Rotter, Tilman B. Drueke, Jurgen Floege, Charles A. Herzog, Gerard M. London, Kenneth W. Mahaffey, Sharon M. Moe, David C. Wheeler, Glenn M. Chertow

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Issue number3
StatePublished - Mar 7 2016

Bibliographical note

Publisher Copyright:
© 2016 by the American Society of Nephrology.


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