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Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.

ABSTRACT: 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.

SUBMITTER: Parfrey PS

PROVIDER: S-EPMC4791832 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.

Parfrey Patrick S PS Block Geoffrey A GA Correa-Rotter Ricardo R Drüeke Tilman B TB Floege Jürgen J Herzog Charles A CA London Gerard M GM Mahaffey Kenneth W KW Moe Sharon M SM Wheeler David C DC Chertow Glenn M GM

Clinical journal of the American Society of Nephrology : CJASN 20151127 3

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 ...[more]

PMID: 26614406

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Dataset Information

Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.

Publications

Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.

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