Rationale and design of a randomized clinical trial to assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy: the Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial

Abstract

Objective: The aim of the study was to describe the rationale, design, and end points of a randomized, double-blind, controlled trial evaluating frequent systematic optimization of atrioventricular (AV) and interventricular (VV) delays in patients receiving cardiac resynchronization therapy (CRT).

Methods: One thousand five hundred eighty heart failure patients, with standard clinical indications for CRT, were enrolled at 178 sites in 16 countries. Within 2 weeks after implantation of a CRT system capable of using a new device-based algorithm for AV and VV optimization, patients were randomly assigned to frequent optimization arm versus empiric device programming or any other non-device-based method of CRT optimization (standard of care arm). In patients in the frequent optimization arm, the AV and VV delays were calculated, reevaluated, and, if necessary, reprogrammed every 3 months. In patients in the standard of care arm, device programming was left to the implanting physician's discretion and remained unchanged throughout the trial unless mandated by a change in clinical status. The primary end point of the trial is the heart failure clinical composite, which classifies patients as worsened, unchanged, or improved based on prespecified definitions. Secondary end points include hospitalizations for cardiovascular reasons and all-cause mortality. End points are adjudicated by an independent committee blinded to study assignment.

Conclusions: The FREEDOM trial, expected to conclude late in 2009, will determine whether frequent optimization of CRT, using a new device-based algorithm, is associated with better clinical outcomes than current standard of care. In addition to improving patient care, this approach might alleviate the workload and economic burden imposed by current approaches to optimization of CRT devices.

Trial registration: ClinicalTrials.gov NCT00418314.