Performance of Centargo: A Novel Piston-Based Injection System for High Throughput in CE CT * The PerCenT Study

The number of contrast-enhanced CT examinations is increasing all over the
world each year. Reasons are easy access, short time to conduct a scan, and
robustness and reproducibility of the examination. Due to the development of
the scanner technology and the availability of Multislice/Multidetector CT, the
time to conduct the scan itself has become shorter and can be less than one
minute depending on the CT system used.

Power injection systems used for contrast-enhanced CT are well-understood
technology with consistent technical capabilities, including ranges of flow
rates, volumes, and pressures. Most common are syringe-based systems, where
empty, disposable syringes are filled from contrast media (CM) bottles and
saline bags. Tubing sets are then used to connect the syringes to the patient*s
cannula/catheter in order to deliver the fluid. The injection system pushes a
piston forward through each syringe, generating sufficient pressure to
administer the programmed injection protocol, which is determined based on a
variety of patient and procedure specific factors. The commercially available
Stellant CT Injection System, which has been on the market for approximately 15
years, is an example of a syringe-based system and will be used as the
comparator device in this study.

While performance of such devices is well-accepted, there are limitations from
an efficiency perspective. The time to prepare the contrast media injection
often takes longer than the image acquisition itself. There are *syringeless*
systems that instead utilize peristaltic pumps to deliver the fluid, which have
been shown to shorten setup and changeover time, but the performance is not
necessarily comparable to a piston-based system. Maximum pressures can be
lower, leading to smaller achievable space, and the pulsatility of the flow is
higher.

The Centargo CT Injection System has been designed to maintain the advantages
of a piston-based system but with the highest possible efficiency, allowing the
radiographer to spend less time handling the injector and disposables and more
time focusing on the patient. This is accomplished with the new disposable
design, which comprises a 24 hour Day Set and a single-use Patient Line. The
Day Set has 3 fluid reservoirs, with 3 corresponding inlet lines (2 for
contrast media and 1 for saline), a manifold, and an outlet line. Instead of
manually assembling the disposables as with Stellant MP (loading syringes onto
the injector, removing dust caps, connecting transfer sets and connector
tubing), Centargo*s Day Set is fully pre-assembled in the package. Reduction
in handling is considered an improvement in hygiene, reducing the risk of
contamination of the fluid path. The patient line, which has dual check valves
to prevent backflow for both Centargo and Stellant MP, has been updated to a
single-click, one-handed insertion for Centargo. The patient end of the
patient line remains connected to the injector until it is time to connect to
the patient.

Other improvements with Centargo compared to Stellant include features to help
prevent air injection and extravasation. Vascular air embolism is a known
risk during a contrast-enhanced CT scan. For systems where fluid path is
visible, it is up to the user to fill, prime appropriately, and check for air.
Other systems, such as those with peristaltic pumps, have inlet and outlet air
detectors. Detected air will lead to an interrupted injection and a potential
repeat of the procedure (including exposure to additional radiation). Centargo
has therefore taken this concern into account in the design. Similar to the
peristaltic pumps, it uses inlet air detectors to prevent filling the Day Set
from an empty bottle, and an outlet air detector will stop an in-progress
injection if it detectors air. However, two other features help to reduce the
risk of an interrupted injection. Air is automatically removed from the Day
Set during filling (using a *vacuum cleaning* procedure), and the differences
in compressibility between fluid and air are used to detect if any air remains
in the reservoir. The Patient Line is also automatically primed as soon as it
is inserted into the injector, eliminating the chance that the radiographer
inadvertently connects an unprimed line to the patient.

For extravasation, the risk is largely related to catheter placement and
patient characteristics and is unrelated to the injector itself. However,
supporting features can aid the radiographer in detecting and preventing
contrast media extravasations. Centargo, unlike Stellant, has a display in the
scan room, so the radiographer can monitor the injection site while
simultaneously viewing the pressure graph. It also allows for live adjustment
of the flow rate up and down during the saline test injection.

Overall, with Centargo, the expected fluid delivery performance is comparable
to other state of the art injection systems, but it also brings improvements in
efficiency and opportunity for greater patient safety.

The aim of the study is to compare an investigational injection system
(Centargo) to the currently available Stellant CT injection system (with
Multipatient disposable kit), in terms of efficiency, cost, performance, and
user satisfaction (phase 1). It is also testing the overall reliability of
the new injection system (phase 2).

This is a randomized multi-center, multi-country prospective clinical study.
Patient population will be adults (* 18 years) already referred for Contrast
Enhanced CT.

The centers* normally defined contrast injection and scan protocols will be
used, with the only difference being injector group * Injector A (Centargo) vs.
Injector B (Stellant MP). Because of the difference in equipment, it will be
clear to which group the subject belongs; therefore it is not possible for the
study to be blinded. No additional injections or scans beyond usual clinical
practice will be performed. Patient participation is only for the time period
of the procedure; the study does not require follow-up measurements or patient
monitoring. The enrollment duration of the study at each center will be
approximately 5 months, with a minimum of 100 subjects per group in the first
phase of the study (see sample size rationale).

For each of the endpoints, data in the eCRF will be used to generate metrics
comparing the two injection systems. Touch time is measured by subtracting
start time from end time for each MP set setup, patient changeover, and MP set
teardown. This will be summed over the course of a 24 hour period for each
injection system and averaged over the length of the study.

Based on the number of MP sets, single patient disposables, and spikes consumed
per day, the total waste will be calculated by volume and by weight, including
packaging. Contrast waste will be measured by the residual contrast in the
system at the end of the day (as recorded by the injection system) and averaged
over the length of the study.
Similarly, each of the disposables has an associated cost, which will be
multiplied by the number of each consumed. This will be divided by the total
number of subjects to obtain a per-patient cost.

For the second phase of the study, testing hardware and software reliability,
no comparator is required. Centargo will be used to perform the power
injection for study subjects. Any error requiring a reboot of the system to
continue will be recorded. Assuming a failure rate of 0.1%, approximately
2000 subjects total are required (see sample size justification); 100 from
phase 1 of the study and an additional 1900 from this second phase.

Known potential risks:
Potential risks of the investigational device are consistent with those of any
commercially available CT power injection system, which are primarily venous
air injection, extravasation, repeat of exam, and infection due to
contamination. Based on verification testing of the requirements for injector
performance and safety, there should be no additional risk to the patient with
use of the investigational device. Testing has been performed to establish
volume and flow rate accuracy, pressure behavior, electrical safety, and
compliance other relevant standards. Any requirements not yet tested have been
assessed with regards to potential patient risk. Detailed risk assessments are
included in the Investigator Brochure. Additionally, onsite training will be
provided to all study sites on the use of the new injection system to ensure
radiographer understanding of labeling and workflow.

Known potential benefits:
Potential benefit to the study population would be increased safety due to new
features available on the injector, such as air detection, automatic priming,
and minimization of handling. While currently marketed power injectors have
excellent safety profiles and are considered well-established, low-risk
devices, the safe use of the device relies on operator expertise, vigilance and
careful handling. Diligence in checking for air, using aseptic technique,
assembling disposables correctly, and setting up the injector are all
required. Centargo provides the opportunity to automate many of those manual
steps. For example, the disposable kit is pre-assembled, does not require
removal of multiple dustcaps and attaching individual tubing sets in the
correct order. The patient line is automatically primed. The number of touch
points and handling is reduced. Ultimately, the potential time and cost
savings in the design of this device could benefit society as a whole,
increasing the accessibility of CT by reducing the time required for
preparation of contrast injections and decreasing costs.

Risk/benefit analysis:
Based on verification testing of the requirements for injector performance and
safety, the risk to the patient with the investigational device should be no
different from the control arm. The study population is subjects already
referred for contrast-enhanced CT. Contrast injection protocols, scanner
settings, and safety precautions in the case of an adverse event are according
to the site*s typical practice, based on the indication for which imaging is
being performed and any patient-specific needs, and will not be affected based
upon which group a patient is randomized.