Pre-Clinical Study; Published Clinical Data - ZOLL AED Plus Administrator's Manual

"... the task force suggests that to demonstrate superiority of an alternative waveform over standard
waveforms, the upper boundary of the 90% confidence interval of the difference between standard and
alternative waveforms must be < 0% (i.e., alternative is greater than standard)."

Pre-Clinical Study

To support pediatric usage for the ZOLL Rectilinear Bi-Phasic Waveform, ZOLL submitted
pre-clinical data to the FDA as part of a 510(k) submission for its AED Plus device (cleared by the
FDA under K033474). The protocol for this pre-clinical study, along with a summary of the results,
have been submitted to FDA under AED Plus PMA application (P160015). A summary of this study
is presented below.
To demonstrate the safety and efficacy of our Rectilinear Bi-Phasic Waveform when used to treat
pediatric VF patients, ZOLL conducted a study using a porcine model of pediatric patients less than
8 years of age. This study included 18 piglets in three (3) size groups (two (2) animals weighing 4 kg,
eight (8) animals weighing 8 kg, and eight (8) animals weighing 16 kg) and compared the
defibrillation dose/response curves observed using proposed biphasic waveform with those observed
using a standard monophasic damped sine wave (DSW) defibrillator to treat short duration (~ 30
seconds) ventricular fibrillation. The study demonstrated that the biphasic waveform defibrillates
pediatric pigs with equal efficacy but lower energy (on a Joules/kg basis) than traditional monophasic
damped sine wave defibrillators. To confirm the safety of the proposed biphasic waveform in
pediatric patients, we studied and compared measures of cardiac function before and after both DSW
and Rectilinear Bi-Phasic Waveform defibrillation shocks over a range of relevant energies. The
study demonstrated that the biphasic defibrillation produced equivalent or milder disturbances of
cardiac function when compared to traditional DSW defibrillation at the same energies.
Another animal study compared the ZOLL rectilinear biphasic (RLB) waveform to a biphasic
truncated exponential (BTE) waveform. The study, using an immature porcine model (n=21), was a
prospective, randomized, controlled design to determine the dose response curves for the RLB and
BTE defibrillation waveforms. A weight range from 4 to 24 Kg for an animal represented a pediatric
patient. The weight ranging from 4 to 8 Kg represented a patient less than 1 year old (infant subgroup),
and the weight range from 16 to 24 Kg represented a pediatric patient between the ages of 2 and 8
years (young children subgroup).
The ZOLL RLB waveform demonstrated a superior capability to defibrillate a porcine pediatric model
with < 90% of the D50 energy required for a BTE waveform (D50 energy: RLB 25.6 ± 15.7 J, BTE
28.6 ±17.0 J, P ? 0.0232; D90 energy: RLB 32.6 ± 19.1 J, BTE 37.8 ± 23.2 J, P ? 0.0228).
The ECG ST segment changes (mV) and LV pressure changes (dP/dt) following a defibrillation shock
were compared between the RLB waveform to the BTE waveform. The RLB waveform had an
average ST segment increase above baseline of 0.138 ± 0.136 mV (N=401 shocks) compared to the
BTE waveform's average increase of 0.146 ± 0.148 mV (N=396 shocks). The RLB waveform had an
average dP/dt at the 40 mmHg threshold (the point in time when an animal's blood pressure exceeded
40 mmHg spontaneously) of 1987 ± 411 mmHg/s (N=496 shocks) compared to the BTE waveform's
average dP/dt of 2034 ± 425 mmHg/s (N=496 shocks).

Published Clinical Data

Additional clinical data was included with PMA application P160015 to support out-of-hospital use
of ZOLL's Rectilinear Bi-Phasic defibrillation waveform. The data reported by Hess et al in
Resuscitation (82 (2011) 685–689) is considered sufficient to support ZOLL's defibrillation waveform
in the out-of-hospital environment. The resulting clinical paper, "Performance of a rectilinear biphasic
ZOLL AED PLUS Administrator's Guide 41