AAA-SHAPE Pivotal Trial: Abdominal Aortic Aneurysm Sac Healing and Prevention of Expansion

An abdominal aortic aneurysm (AAA) is an enlarged area in the lower aorta. Over
time, this enlargement (often called an aneurysm sac) can become weak, and the
force of normal blood pressure can cause it to expand and rupture. This can
lead to hemorrhage and death.

The prevalence of AAA is 4-8% worldwide and increases in people >60 years. The
main risk factors for AAA are increased age, male gender, smoking,
hypertension, atherosclerosis and a family history of AAA. As men are 4 times
more likely to develop an AAA, it is recommended that men should be screened
for AAA beginning at 65 years of age. AAAs are difficult to detect as they are
largely asymptomatic unless they are rapidly expanding or ruptured. They are
mostly detected during abdominal imaging for another indication.

Left untreated, an AAA is at risk of continued growth and rupture. AAA risk
factors include smoking, high salt intake, high blood pressure, concomitant
peripheral arterial disease and cerebrovascular disease, and family history of
AAA. Elective repair is recommended for AAA >=5.5 cm in diameter in men and >=5.0
cm in women.

Left untreated, the aneurysm will continue to grow and will eventually rupture.
Ruptures are harder to treat, and 80% of ruptures result in death.
Biomechanical stresses on the artery, such as greater flow lumen volume and
lower thrombus burden (defined as the percentage of the AAA sac volume occupied
by thrombus), increase the risk of rupture. Aneurysms with higher thrombus
burden are less likely to grow. Therefore, thrombus burden is a factor that
could be used for risk stratification when planning how and when to treat AAA.

The decision to treat an AAA is based on several factors, including the size of
the aneurysm and comorbidities of the patient. AAAs can be managed medically if
they are small (*watch and wait*), but when the risk of rupture outweighs the
risk of treatment, they can be treated with open surgical repair or with the
less invasive option of endovascular aortic repair. When the decision has been
made to treat the aneurysm, there are two options, namely open surgical repair
and EVAR. Open surgical repair (OSR) of AAA is a common and durable treatment
option for patients with AAA; however, this invasive operation is associated
with increased short-term morbidity and mortality.

EVAR, a less invasive alternative to OSR, employs a covered stent graft to
exclude the aneurysmal sac from blood flow and pressure and prevent the walls
of the aneurysm from further expanding and potentially rupturing. Nearly half
of the aneurysms treated with EVAR do not regress, which continues to place the
aneurysm at risk of rupture. This failure to regress, or continued sac
expansion, can occur after EVAR either because of the natural history of the
aneurysm disease process and the aneurysm*s failure to heal, or from Type II
endoleaks (persistent filling and pressurization of the aneurysm sac that
originates from collateral arteries that branch off of the aorta). Therefore,
changes in dimension of the aneurysm sac should be monitored following EVAR. As
changes in sac size occur in 3 dimensions, both changes in sac diameter and
volume can be used to define aneurysm size according to the reporting standards
for EVAR.
When the aneurysm sac continues to expand, whether or not associated with Type
II endoleak, increased imaging surveillance is required. Often, continued
aneurysm sac expansion results in a significant rate of secondary procedures,
rehospitalizations, and an increased risk of all-cause mortality. The following
points highlight the primary risks when the aneurysm sac fails to regress after
EVAR:
• Sac expansion (> 5 mm) at 1 year was independently associated with late
mortality, regardless of the presence or absence of endoleak. This data was
obtained from all patients (n=2,437) undergoing EVAR between 2003 and 2011.
• A follow-up study using data from the full Vascular Quality Initiative
between 2003 and 2017 from 14,827 patients found that patients with both
expanding and stable sacs are at a greater risk of all-cause mortality, not
aneurysm-related mortality. This affects the majority of EVAR patients, as the
majority of aneurysms fail to regress (i.e., 60%).
• The ENGAGE global post market study between 2009 and 2011 of the world*s most
commonly used stent graft, the Medtronic Endurant, showed again that sac
expansion and stable sacs at one year were associated with an increase in late
mortality compared to those with sac regression.
• An analysis in 2020 of the latest data collected from the ENGAGE post market
registry showed that patients with regressing sacs at 1 year had statistically
significant better freedom from all-cause mortality and freedom from secondary
endovascular reinterventions than patients with stable or expanding sacs.
• A recently published meta-analysis from 17,096 patients in the UK showed that
patients without sac shrinkage, which was seen in 52% of all patients, had a
significantly higher hazard of all-cause and AAA-related death, secondary
intervention, late complications, and rupture.
• Real world data prospectively collected from 1997 through 2011 from 1,412
patients shows 35% to 50% of EVAR patients undergo secondary intervention
within 2 to 5 years.
• At the recent public advisory meeting of the Circulatory System Devices Panel
of the Medical Devices Advisory Committee hosted by the Food and Drug
Administration (FDA) on November 2-3, 2021, a retrospective review of 1,835
EVARs performed between 2000-2016 from the University of Pennsylvania was
presented. In this review, the overall re-intervention rate was 7.5%.
Importantly, 55% of re-interventions were due to Type II Endoleak , and the
most common cause of open conversions was sac expansion.

The need for reinterventions remains the Achilles heel of EVAR. However, there
is strong evidence to show that sac regression is associated with reduced
reintervention rates as well as aneurysm-related and cardiovascular morbidity
and mortality. Strategies to increase the likelihood of sac regression will
improve EVAR outcomes.

As mentioned above, reinterventions are EVAR*s weak spot. Endoleaks are the
most frequent complications of EVAR and the main cause for clinical failure,
with frequency reported rates ranging from 2.4 to 45.5%. Lifelong follow-up is
necessary for patients who underwent EVAR, for monitoring of changes in sac
size, possible undesirable side-effects (including endoleaks), and for the
assessment of long-term success of EVAR. Computed tomography (CT) is commonly
used for patient follow-up and is highly accurate in the detection of endoleaks.

CT imaging is used to monitor changes in aneurysm sac size and can be used to
measure both diameter and volume. Diameter is commonly used to monitor changes
in sac size. However, changes in sac volume are critically important as they
indicate the long-term success of EVAR by taking into account that variations
in size occur in 3 dimensions, and small changes in diameter may not reflect
the overall change in shape of the aneurysm. Reconstructive volumetric
measurement can be used to combine two-dimensional axial sections taken from
different reference levels, and these section are then converted into a
three-dimensional image to obtain volumetric measurements. Using volume
analysis, Figure 3 (see protocol p. 23) shows that a 25 % increase in aneurysm
volume can be associated with an insignificant increase in diameter (<5 mm),
and diameter can vary greatly depending on the measurement technique and the
choice of plane. Since volumetric measurements are three-dimensional, they are
able to detect minor changes compared to two-dimensional diameter changes.
Two-dimensional measurements would be especially inadequate in areas with an
irregular aneurysm wall. Therefore, both volume and diam

The purpose of the pivotal study is to determine the safety and efficacy of
IMPEDE-FX RapidFill for increasing the percentage of subjects with shrinkage of
the abdominal aortic aneurysm sac when used as an adjunct to on-label EVAR
stent graft treatment in subjects eligible for elective EVAR.

The clinical trial is a prospective, multicenter, randomized, pre-procedure,
single-blind, open-label study. This study is a pre-procedure, single-blinded
study, i.e. subjects are blinded to the treatment arm before the procedure;
after the procedure, they will be unblinded prior to discharge to prevent
unintentional unblinding due to imaging.
The randomized study has two arms, as described below:
- Treatment arm: Subjects in the treatment arm will have both an EVAR device
and IMPEDE-FX RapidFill implants implanted.
- Control arm: Subjects in the control arm will have only an EVAR device
implanted.
Subjects will be randomized in a 2:1 ratio (treatment: control).
In the treatment arm, a minimum of 10 grafts from each EVAR manufacturer (see
procedural exclusion criteria #1 for details) must be used throughout the
study.

The procedure at which the Aortic Stent Graft (for the Control arm) and the
IMPEDE-FX RapidFill System (for the Treatment arm) is considered the index
procedure/treatment for this clinical trial. The IMPEDE-FX RapidFill System
procedure will be completed under fluoroscopic guidance; refer to the
corresponding device IFU regarding the specific steps for device access,
deployment, and withdrawal.

Subjects enrolled in the trial will participate for a duration of 5 years with
visits at 30 days, 6 months, 1 year and annually thereafter through 5 years
after the index procedure.

Each potential subject will be evaluated as to whether they meet all of the
inclusion criteria and none of the exclusion criteria for enrollment in the
trial. Assessments included for screening/baseline assessment are those that
are generally done as part of standard of care.
The following screen/baseline assessments will be completed at the screening
visit prior to the index procedure. All data from these assessments must be
reported on the respective case report form.
• Demographic information
• Health Related Quality of Life Questionnaire
o Pre-procedure Dartmouth (*People Living with an Abdominal Aortic Aneurysm*)
o SF-12
• Medical history, including any risk factors.
• Physical exam, including abdominal and peripheral pulse examination.
• Contrast enhanced CT
o CT slice size: 1.5 mm or thinner
o CT characteristics: contrast
o Location: from the level of the diaphragm to the common femoral bifurcations
o Timing of the imaging: CT that is completed within 4 months of the index
procedure.
• Blood count (CBC, creatinine, CRP)
o Timing: within 3 months maximum from the index procedure

The procedure at which the Aortic Stent Graft (for the Control arm) and the
IMPEDE-FX RapidFill System (for the Treatment arm) is considered the index
procedure/treatment for this clinical trial. The IMPEDE-FX RapidFill System
procedure will be completed under fluoroscopic guidance; refer to the
corresponding device IFU regarding the specific steps for device access,
deployment, and withdrawal.
The following data (not an all-inclusive list) will be recorded on the
respective Treatment Case Report Form:
• Total Endovascular time; from initial catheter introduction to last catheter
removal
• Total IMPEDE-FX RapidFill procedure duration from catheter introduction to
catheter removal (for the Treatment Arm)
• Anesthesia time
• Fluoroscopy time (contrast volume, time, radiation exposure)
• Contrast volume
• Access method and site
• Total radiation exposure
• Additional imaging
• Presence of intraprocedural endoleak, prior to IMPEDE-FX RapidFill Implant
insertion (for the Treatment Arm) and at the conclusion of the index procedure
• Technical success
• Additional procedures performed during the index procedure, including type of
device(s) used and reason for use
• Additional (ancillary) devices implanted/utilized during the index procedure
that are related to the trial treatment
• Identification numbers for all investigational components
• Estimation of blood loss
• Procedural complications
• Time in ICU
A copy of the procedural angiogram may be requested by Shape Memory Medical.
Subjects who consent, are randomized into the treatment arm, have any part of
the IMPEDE-FX RapidFill System introduced into their body but either treatment
is not attempted or is unsuccessful (zero IMPEDE-FX RapidFill Implants
inserted), will be considered *Intent to Treat* subjects. These subjects will
be followed for 30-days for safety only, and thereafter per institutional
standard of care. Intent to Treat subjects will count towards the total
enrollment number of up to 180 subjects and will be included in the analysis of
safety data.
If a subject is converted to open surgical repair at any point in the trial,
and the IMPEDE-FX RapidFill Implants are removed, the subject will be followed
for 30-days for safety only, and thereafter per institutional standard of care.

Subjects will be evaluated from the time that the IMPEDE-FX RapidFill System
(for the Treatment Arm) and the endovascular graft (for the Control Arm) is
implanted through hospital discharge. The following information will be
captured on the respective CRF:
• Duration of hospital stay (in hours)
• Adverse event assessment
• Duration of intensive care unit after index procedure (in hours)
• Groin evaluation
• Abdominal examination
• Post-implantation Syndrome assessment
o CBC, temperature, CRP

Subjects will complete follow-up visits at 1 month (30 days ± 14 days), 6
months (180 days ± 4 weeks), 1 year (365 days ± 4 weeks), and annually
thereafter through 5-years post procedure (± 4 weeks).
At each of these visits, the following will be obtained:
• Physical exam (including incision site assessment for the 1-month follow-up)
• Health Related Quality of Life Questionnaire
o Post-Procedure Dartmouth (*People who have had surgery to Repair an Abdominal
Aortic Aneurysm*)
o SF-12
• CT scan with contrast will be obtained.
• Abdominal X-ray will be obtained (3 view KUB). Only required at the 1 year, 3
year, and 5 year visits.
• Duplex Ultrasound will be obtained.
In the case that a CT scan is performed before the 1-month follow-up, the first
post-procedure CT can substitute for the 1-month CT, as long as it is acquired
within 37 days.
Requirements of the CT imaging will be as follows:
• CT slice size: 1.0 mm or thinner
• CT characteristics: three-phase study (non-contrast, contrast, and delayed)
• Location: from the level of the diaphragm to the common femoral bifurcations
Based off of the CTA, at each of these visits, the following assessments will
be completed by both the site and Core Lab:
• Assessment for EVAR stent graft integrity (fracture) which will be evaluated
by abdominal X-ray with at least 2 obliquities.
• Evaluation for the following:
o EVAR-related observations, including endoleaks, patency and migration
(measured against the 30-day CT)
o Evaluation for IMPEDE-FX RapidFill Implant migration (implants outside of the
aneurysm sac)
o Aneurysm diameter
o Graft limb patency
o Renal artery patency
Additionally, the following assessments will be completed by sites:
• Collection of any adverse event information.
• Post-implantation syndrome assessment at the 1-month visit.
o CBC, temperature
• C-reactive protein

After the index procedure, additional interventions may be needed that may be
related to the Aortic Stent Graft, the IMPEDE-FX RapidFill System (for the
Treatment Arm), and/or the underlying lesion. Information regarding these
interventions will be captured on the respective CRF.
The following information regarding any secondary interventions completed will
be captured:
• type of secondary intervention
• reason of secondary intervention
• time from index procedure
• collection of any adverse event information
• any device(s) used during the secondary intervention
If a subject requires explantation of the IMPEDE-FX RapidFill Implants, the
subject will be followed for 30-days or until hospital discharge, whichever is
longer, for safety and then will exit the trial.

If a subject returns for an unscheduled visit (i.e., between the protocol
defined follow-up visits) regarding the treated aneurysm, the specific
assessments completed will be at the discretion of the treating physician. The
following will be documented on the respective CRF, as well as the following:
• Reason for unscheduled visit
• Date of the visit
The following additional information will be documented on the respective CRF,
as applicable:
• Assessment of the Aortic Stent Graft, as well as the IMPEDE-FX RapidFill
Implants (for the Treatment Arm)
• Evaluation for the following based on contrast enhanced CT and adjudicated by
the Core Laboratory:
o Graft device-related observations, including endoleaks, and patency,
o Evaluation for Aortic Stent Graft and/or IMPEDE-FX RapidFill Implant migration
o Aneurysm diameter
o Graft limb patency
o Renal artery patency
• Collection of any adve