38 Stratos LV/LV-T Technical Manual

Primary Effectiveness Endpoint Analysis and Conclusions

The primary effectiveness endpoint evaluated CRT effectiveness (Groups 1 and 2) compared to RV only effectiveness (Group 3), as measured by the composite rate of the six minute walk test and QOL improvement from Baseline to the Six-Month follow-up (Table 8). For this analysis, both six minute walk test and QOL were equally weighted at 50%. Due to the small number of patients with data available for the analysis of the primary endpoint, the results lack power to demonstrate that biventricular pacing with either the Protos DR/CLS or Stratos LV device is statistically different from RV only pacing with the Stratos LV device in patients undergoing an “ablate and pace” procedure.

Multi-site Poolability and Gender Analysis

The AVAIL CLS/CRT clinical report included data from multiple centers with centralized coordination, data processing, and reporting at BIOTRONIK. All of the clinical centers followed the requirements of an identical clinical protocol, and all of the clinical centers used the same methods to collect and report the clinical data, including New York Heart Association evaluation, six-minute walk test, Minnesota Living with Heart Failure questionnaire, and echocardiographic measurements. In order to justify pooling of the data from multiple centers, several analyses were completed. All of the centers were divided into two groups (Small and Large sites) based on implant volume. Comparisons were then made between the patient populations based on the results of the safety and effectiveness endpoints. Additionally, analyses were performed on the data collected in the AVAIL clinical investigation in order to compare results between males and females. The first type of analysis compared enrollment by patient gender in each of the study groups. The second type of analysis compared effectiveness and safety outcomes in each gender.

The results of these analyses demonstrated poolability of the data between sites. There were no significant differences in the primary safety or effectiveness endpoints between high and low volume implant centers.