Multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT): design and clinical protocol

Abstract

The planned MADIT-CRT trial is designed to determine if CRT-D will reduce the risk of mortality and HF events by approximately 25% in subjects with ischemic (NYHA class I-II) and non-ischemic (NYHA class II) cardiomyopathy, left ventricular dysfunction (EF<or=0.30), and prolonged intraventricular conduction (QRS duration>or=130 ms).

Figure 1

Schematic presentation of the group‐sequential design and the associated stopping boundaries (dashed lines). The vertical axis is a measure of the observed treatment differences (efficacy). The horizontal axis is a measure of information collection (mortality or heart failure events, whichever comes first). Stopping boundaries are prespecified for benefit of CRT‐D or ICD‐only, or no difference. Examples of possible outcomes are provided by the three arrows: A = early termination for CRT‐D benefit; B = termination for no difference between the two treatments; C = early termination for ICD‐only benefit. Reaching the upper (lower, respectively) boundary will result in an estimated hazard ratio of <0.85 (>1.18, respectively); an estimated hazard ratio between 0.85 and 1.18(1/0.85) is consistent with a “no difference” conclusion. The 20 prespecified analyses are scheduled at approximately equal information times.

Figure 2

Flow diagram of enrollment cascade.

Figure 3

MACIT‐CRT organizational chart.