Use Instructions

63
Primary Safety Endpoint
The primary safety endpoint was the composite endpoint of the percentage of subjects in
the OPTIMIZER group who experienced either an OPTIMIZER device or OPTIMIZER
procedure related complication through the 24-week follow-up period, as determined by
an independent events adjudication committee (EAC). The EAC reviewed all serious
adverse event reports (SAEs), confirmed the classification of “serious”, and adjudicated
the relationship of the event to the OPTIMIZER System device or procedure. SAEs that
the EAC determined to be definitely related to either the OPTIMIZER System or the
OPTIMIZER Procedure were considered a Complication.
There was only 1 complication observed in the FIX-HF-5C2 subjects. This was in a
subject who had a minor hematoma at the OPTIMIZER IPG implant site and was kept in
the hospital overnight for observation following the device implantation. The hematoma
resolved without treatment, and there were no further complications in this case. The
EAC adjudicated the event as a procedure related complication to account for the index
hospital stay being prolonged an additional day for observation. There was no
OPTIMIZER device-related SAE reported in the 2-lead device subjects.
Thus, the complication rate in FIX-HF-5C2 study ITT group was 1.7% (1/60) with exact
95% CI (0.0%, 8.9%). As can be seen in Table 20, the rate of complications in the FIX-
HF-5C2 study was nominally lower than seen in the previous study although not
statistically significant. The small sample size for the FIX-HF-5C2 study renders it difficult
to show a statistical difference in percentage points. However, the absolute difference
between the complication rate for the FIX-HF-5C2 study (1.7%) and the FIX-HF-5C study
(10.3%) is clinically relevant.
We can therefore conclude that the primary safety endpoint of the FIX-HF-5C2 study was
met and that delivery of CCM through a 2-Lead device is just as safe as delivery of CCM
therapy through a 3-Lead device. These results may, in part, be due to a reduction in the
number of leads implanted with the 2-Lead device as well as the reduction in the total
volume of leads introduced in the venous vasculature.
Table 20: Safety: ITT Population
FIX-HF-5C2
FIX-HF-5C
Variable
OPTIMIZER 2-
lead
OPTIMIZER 3-
lead
P-value
1
Primary Safety
OPTIMIZER device- or
procedure-related
complication through 24
Weeks
N (%)
1 (1.7%)
7 (10.3%)
0.0660
[95% CI]
(0.0%, 8.9%)
(4.2%, 20.1%)
Secondary Safety
PVC or VT SAEs
N (%)
0 (0.0%)
0 (0.0%)
PVC
N (%)
0 (0.0%)
0 (0.0%)
VT
N (%)
0 (0.0%)
0 (0.0%)
1
Compared to FIX-HF-5C2 OPTIMIZER Group via Fishers exact test.
*Values are number and percent of subjects. Subjects are counted only once within each
category.