A Study of the Safety, Efficacy, Longitudinal Costs and Patient-Centered Outcomes Using a TAAA Debranching Device
Phase: NA
Conditions: Thoracoabdominal Aortic Aneurysm
Sponsor: Johns Hopkins University

Study Title  
A study of the Safety, Efficacy, Longitudinal Costs and Patient 
Centered Outcomes using a TAAA Debranching Device 
Sponsor-Investigator 
James Black, MD 
NCT Number  
NCT03637374 
Document Description  
Study Protocol and Statistical Analysis Plan 
Document Date  
30-Jun-20 
 

Date: June 30, 2020    
Principal Investigator: James Black 
Application Number: IRB00075706 
 
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JHM IRB - eForm A – Protocol Version 5.0 
 
 
 
A study of the Safety, Efficacy, Longitudinal Costs and Patient-Centered Outcomes  
using a TAAA Debranching Device 
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1. 
Abstract 
a. Provide no more than a one page research abstract briefly stating the problem, the research 
hypothesis, and the importance of the research. 
 
 
This study seeks to define longitudinal one year costs of delivery of care for patients who undergo 
care for complex aortic aneurysm disease.  While surgery remains a standard treatment for complex 
abdominal and thoracoabdominal aneurysms (TAAA), the tolerance of the older patient to recover such 
extensive and brutally invasive open aortic reconstructions is poor.  Endovascular may offer the 
opportunity to reduce patient risk with less invasive approaches, improve quality of life, and serve to 
reduce the cost burden to payors which encumbers such difficult surgeries.  In this study, we will compare 
the one year costs of inpatient and outpatient care associated with complex aortic repairs, comparing both 
the open surgical and endovascular approach with a TAAA debranching technology to solve this difficult 
clinical scenario, in our hospital wherein we have established expertise in management of patients with 
aortic diseases and it protean manifestations.   
 
 
The results of this study will serve to identify safety endpoints of endovascular technology of a 
TAAA debranching system, provide transparent data concerning both inpatient and outpatient costs of open 
and endovascular surgery in the older patient group, and patient perceptions about their care and its impact 
on their quality of life. Commensurate with goals of the Affordable Care Act provisions to examine clinical 
effectiveness and cost containment, this study may form the basis for refinement of technology used in 
aortic care which can motivate episode-based payment methods and further develop proper risk adjustment 
assessments for open and endovascular surgery considerations in the future. 
 
2. 
Objectives (include all primary and secondary objectives) 
 
Primary 
 
The primary safety endpoint is freedom from major adverse events (MAE) at 30 days or during 
hospitalization if this exceeds 30 days. Major adverse events include death, bowel ischemia, 
myocardial infarction, paraplegia, renal failure, respiratory failure, and stroke. 
 
The primary effectiveness endpoint is the proportion of study subjects with treatment success at 1 
year. Treatment success is defined as a composite of technical success and freedom from the 
following:  
• Aneurysm enlargement i.e., >5mm as compared to any previous CT measure using orthogonal (i.e, 
perpendicular to the centerline) measurements 
• Aneurysm rupture 
• Aneurysm-related mortality 
• Conversion to open repair 

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• Secondary intervention for migration, Type I and III endoleaks, device integrity failure (e.g., 
fracture), and patency-related events (i.e., device component stenosis or occlusion and embolic 
events) 
 
The primary non-technical endpoint is improvement in quality-of-life scores (by SF36) and reduced 
1 year costs for patients who undergo endovascular repair vs open surgery.Secondary 
 
 
Secondary endpoints include: 
• Technical success and the individual components of technical success: 
o Successful delivery 
o Deployment at the intended implantation site 
o Patency of all endovascular graft and stent components 
o Absence of device deformations requiring unplanned placement of an additional 
device 
o Absence of inadvertent covering of aortic branch vessels 
o Successful withdrawal 
• Freedom from the individual components of the primary safety endpoint at 30 days.   
o Death 
o Bowel ischemia 
o Myocardial infarction 
o Paraplegia 
o Renal failure 
o Respiratory failure 
o Stroke 
• Freedom from paraparesis at 30 days 
• Treatment success and the individual components of treatment success including freedom 
from the following at each follow-up interval: 
o Aneurysm enlargement 
o Aneurysm-related mortality  
o Aneurysm rupture 
o Conversion to open repair 
o Secondary intervention for: 
o Migration 
o Type I endoleak 
o Type III endoleak  
o Device integrity failure (e.g., fracture)  
o Patency-related events (i.e., device stenosis or occlusion and embolic events)  
o Renal failure 
o All-cause mortality 
o Endoleaks 
o Device integrity failure (e.g., fracture) 
o Patency –related events (i.e., endovascular graft or stent component stenosis or 
occlusion and embolic events) 
o Other device-related events 
 
 
3. 
Background (briefly describe pre-clinical and clinical data, current experience with procedures, 
drug or device, and any other relevant information to justify the research) 

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Purpose 
The primary objective of the clinical investigation is to assess the use of the Valiant 
Thoracoabdominal Stent Graft System to repair thoracoabdominal aortic aneurysms in patients having 
appropriate anatomy, as measured by device safety and preliminary effectiveness, costs of delivery of 
aortic surgery care, and patient quality of life domains. The study titled:   A study of the Safety, Efficacy, 
Longitudinal Costs and Patient-Centered Outcomes using a TAAA Debranching Device. Within this 
objective is the primary technical intent of the study is to assess safety acutely (i.e. freedom from major 
adverse events (MAE) at 30 days) and preliminary effectiveness (i.e., treatment success and technical 
success) of the device (i.e., the proportion of treatment group subjects that achieve and maintain treatment 
success at one year).   Additionally, the study will assess technical success and treatment success at each 
follow-up interval.  
 
The primary non-technical endpoint of the study will also measure patient quality of life by validated 
SF36 surveys at treatment and each follow-up interval and the cost to deliver the care of aortic surgery. 
 
Report of Prior Investigations. 
Anatomy 
The aorta is the main artery that originates in the left heart chamber, ascends to the arch, and 
descends through the thoracic cavity and diaphragmatic muscle into the abdomen. The aorta gives a 
number of side branches throughout its trajectory from the mediastinum to the chest and abdomen. These 
branches include the coronary arteries, innominate artery, left common carotid artery, left subclavian artery, 
celiac axis (CA), superior mesenteric artery (SMA), renal arteries and inferior mesenteric artery (IMA) and 
various lumbar arteries. The aorta terminates at the aortic bifurcation where it divides into the common iliac 
arteries. Several smaller parietal side branches originate throughout the length of the aorta and include 
bronchial, intercostal, phrenic and lumbar arteries. A number of anatomical variants and accessory 
branches have been described. Approximately 15% to 30% of individuals have one or more accessory renal 
arteries. The hepatic arteries can originate as a separate branch from the aorta, or as replaced branches from 
the left gastric or SMA in 5% to 15% of individuals1. In addition to accessory or replaced anatomy, the 
diameter, location and angle of the visceral arteries have significant variation, which may have implications 
with respect to arterial hemodynamics.  
Pathophysiology 
Aortic aneurysm is a progressive disease characterized by structural deterioration, gradual 
expansion, and eventual potential for rupture of the aorta if left untreated. The definition of aortic aneurysm 
is a localized or diffuse dilatation encompassing all three layers of the aorta with diameter >50% larger than 
the expected normal aortic diameter.   
An aneurysm which spans both the thoracic and abdominal cavities defines a thoracoabdominal 
aortic aneurysm.  The expansion rate of thoracoabdominal aneurysms ranges from 2-4mm per year and is 
not influenced by the size of the aneurysm at the time of diagnosis2,3.  The expansion rate of 
thoracoabdominal aneurysms does not appear to increase as individual aneurysms enlarge.  The presence of 
COPD and hypertension are factors associated with an increased rate of enlargement4,5.  Thoracoabdominal 
aortic aneurysms become a risk for rupture if they are above 5.5-cm in diameter or if they are less than 5.5-
cm in diameter and are growing more rapidly than 0.5-mm in 6 months.  The 5-year survival of 
thoracoabdominal aneurysm patients ranges from 7-20% depending on the percentage of aneurysms 
secondary to aortic dissection3,6.  Half of the thoracoabdominal aneurysm deaths are attributed to rupture 

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and the other half are due to some sort of comorbidity such as myocardial infarction.  The overall survival 
of thoracoabdominal aortic aneurysm patients is often overestimated, because the patients with advanced 
comorbid medical illness are not included and account for 46-68% of the patients reported in past natural 
history studies3,6-9.  Dissecting aneurysms have a higher rate of rupture and have a worse prognosis without 
intervention. 
Most patients with a descending thoracic or thoracoabdominal aneurysm do not have symptoms 
when first diagnosed7,10.  They are likely diagnosed with a CT scan for another disease.  Some patients 
have vague chest, back, flank, or abdominal pain.  The pain may increase in severity as the aneurysm 
enlarges, or it may be sudden due to rapid expansion and impending rupture.  Symptoms can result from 
compression of or erosion into adjacent intra-thoracic structures or bony thorax7,11,12.  Hoarseness from 
stretching or compression of the left recurrent laryngeal nerve, tracheal deviation, persistent cough, or other 
respiratory symptoms are sometime seen.  Patients with a thoracoabdominal aortic aneurysm may have a 
palpable pulsatile mass in the upper abdomen.   
 
Emergent/Urgent/Ruptured Aneurysms 
A ruptured aneurysm is either an emergent or urgent situation and many times is fatal carrying an 
overall mortality rate of 90%.  Ruptures present in many different ways.  One study states that 80% of 
ruptures present as a retroperitoneal rupture13.  A retroperitoneal rupture can lead to slow progressive 
bleeding which forms a large hematoma that is contained by the periaortic tissues.  Approximately 4% of 
ruptured aneurysms are contained ruptures.  Surgical treatment is recommended within 24 hours of 
presentation of a contained rupture.  An acute ruptured aneurysm requires immediate intervention and it is 
said that endovascular techniques may improve the survival for patients with ruptured aneurysms13.   
In a combination of retrospective and prospective IDE data from other sites (G140207), there have 
been 3/33 subjects treated emergently and 3/33 subjects treated urgently.  Of the three treated emergently, 
there were no intraoperative deaths.  All of the emergent subjects had prior open repair that failed and were 
left with at least one major complication from prior open surgery.  One died on day 14, one was discharged 
and presented with an acute onset of paraplegia and passed away at 30 days, and one survived to 3 months.  
Recent results have reported the mortality rate of emergent/urgent open repair to be 43% with the average 
visceral ischemic time of 36 minutes with average blood loss of 2875cc14.  Another center reported a 36.8% 
30-day mortality in patients treated with a hybrid approach15.  Comparison of this study with prior results 
of open repair and the fact that there was no ischemic time and an average blood loss of 1250 cc in 
emergent cases from prospective IDE data, the probable risk of the using the investigational device is no 
greater than the probable risk of open repair or from the disease.   
Three subjects were treated urgently requiring repair within one week of presentation.  One subject 
treated urgently was doing well at his 30 day visit and succumbed to a hemorrhagic stroke at 35 days, one 
died of leukemia at 14 months, and one is nearing her three year visit and is doing well.  Of the subjects 
treated urgently, none of them died of aneurysm or device related deaths and all but one survived past one 
year.     
Presentation of a subject requiring emergent treatment needs to be treated immediately while urgent 
treatment needs to be completed within a week of presentation.  Due to the many comorbidities of these 
subjects, an open repair is not recommended for the same reasons as an elective open procedure.  
Therefore, we feel that treatment with this investigational device is warranted to minimize the risks 
associated with open repair.  This device is an endovascular option that can be used off the shelf and 
delivered quickly to treat an emergent case while reducing the procedure time and overall blood loss.  Due 

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to the high overall mortality of open repair, the probable risk of the investigational device is no greater than 
the probable risk from the subject’s condition.  While these subjects would benefit from the investigational 
device, these subjects should not be included in the primary study arm as the expanded selection criteria 
could present confounding results making it challenging to separate the safety and effectiveness of the 
device from the underlying disease process.   
Type B Dissections 
A Stanford type B dissection begins distal to the brachiocephalic artery.  We plan on treating both 
type B dissections that are subacute and chronic with aneurysmal changes.  Treating dissection subjects 
involves determining the true and false lumens and which lumen feeds the visceral vessels.  The visceral 
manifold device design does not mimic natural anatomy and has the ability to cross between true and false 
lumen to treat the dissection, feed the visceral vessels, and accommodate the device even in a small true 
lumen by utilizing both the true and false lumen as conduits to complete the case.  Our device can cross 
between naturally occurring fenestrations or a laser may be used to create a fenestration between the true 
and false lumen.  The risks of using a laser to create fenestrations include perforating the aorta or branch 
vessels, extension of the dissection, vascular trauma, embolism, pseudoaneurysm, and bleeding.  These 
risks will be mitigated by utilizing the smallest possible laser and using fluoroscopic guidance to locate and 
create the area for the fenestration.  The risk of potential dissection extension in chronic type B dissections 
is very low.  The risk of potential dissection extension is higher in subacute type B dissections and would 
be mitigated by controlling blood pressure while deploying, conservative oversizing of the stent graft, and 
having a cardiothoracic surgeon available if there is a retrograde dissection.   
A large number of these patients have been excluded from that study for dissection. 15% (5/33) of 
subjects were treated electively for TAAA with a dissection (G140207). A laser was used to perforate the 
aortic wall between the lumens to allow for placement of the graft and limbs when a natural fenestration is 
not found.  All of the procedures were successful and there were no device related events or disease related 
mortalities. Type II endoleaks were observed in 2 of the 5 subjects, but have not required intervention or 
lead to aneurysm enlargement. 60% (3/5) of these subjects are doing well at two years post procedure. Of 
the two that are deceased, one died of a CVA at four months while the other death was self-induced due to 
alcohol abuse post procedure.  Literature cites an in-hospital mortality rate of 29% for open surgical repair 
of type B dissection.  Given the small population treated with the branched endograft to date with no 
mortalities related to the device or the dissection, we believe the patient population presenting with type B 
aortic dissection involving the visceral segment could benefit from the use of this device over currently 
available options.  These subjects should be included in the expanded selection arm rather than the primary 
study arm due to presentation with a concomitant disease process that falls outside the study’s intended use.   
Aneurysm with Renal Insufficiency 
Subjects with known renal insufficiency and renal failure are excluded from the primary study arm 
due to underlying renal insufficiency that increases their risk of peri-operative renal failure confounding the 
differences between the efficacy of the device and the underlying disease process.  This device would still 
be beneficial for this subject population because it allows for continued perfusion of the renal arteries and 
may in some instances treat underlying causes for renal insufficiency.   
A 2004 report that evaluated the outcomes of aneurysm repair in patients with established renal 
failure reported that subjects presenting with chronic renal impairment have a high incidence of concurrent 
cardiovascular morbidity and are at high risk for aneurysm disease.  They also reported that aneurysm 
subjects with renal dysfunction that were non-operative had a 20% 5-year survival rate, with 39% of 
subjects dying from rupture of their aneurysm.  One study cited a 25% mortality in subjects on 

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hemodialysis and 67% of subjects with renal insufficiency (creatinine >4 mg/dl) requiring post-operative 
dialysis16.  Several precautions are put into place to protect renal function during the procedure including 
hydration, a minimal volume of nonionic contrast agent, and continual monitoring of post procedure 
creatinine levels.  Subjects undergoing dialysis at the time of procedure will be dialyzed before and after 
the procedure to protect any remaining renal function. One research study indicates that elevated creatinine 
levels don’t indicate post-op renal failure and that the creatinine level may not be a contraindication for 
EVAR treatment if proper precautions are used17.      
Aneurysms with Small Branch Vessels <5 mm 
Small branch vessels less than 5 mm are excluded from the primary study arm due to an increased 
risk of increased intimal hyperplasia, branch occlusion, and potential end organ failure.  These same 
principles are true even in open bypass surgery.  These subjects would still benefit from the use of this 
device due to the gradual sweeping endobypasses that deliver more developed flows to reduce the risk of 
branch vessel occlusion.  Additionally, it is extremely rare to see a SMA with a diameter less than 5 mm 
therefore reducing the risk of fatal branch occlusion.  These subjects will still benefit from exclusion of the 
aneurysm and reduced risk of aortic rupture.  Due to the significant mortality associated with rupture or 
open repair, this patient population is willing to assume a higher risk of renal insufficiency or renal failure.    
When treating subjects with impaired renal function, there is an increased probability of subjects 
having renal arteries < 5 mm or underlying significant stenosis.  While this is our current requirement, there 
have been eight subjects treated with a renal artery less than 5 mm at other sites and one subject with a 
celiac artery measuring less than 5 mm.  These subjects had no adverse events related to the treatment of a 
smaller vessel.  As we open the criteria to increased comorbidities, there will be more subjects presenting 
will smaller vessels.  Current technologies, including T-branch and fenestrated stent grafts, treat vessels 
with diameters ranging from 4-8 mm. 
 
Aneurysms with Prior Repair  
The need for a redo procedures in TAAA repair is common and is primarily due to extension of the 
aneurysmal disease18.  Other causes for a late redo procedure include including para-anastomic aneurysms, 
pseudo-aneurysms, stent graft migration, type I endoleaks, graft infection, or fistulas19.  Natural history 
studies and literature reviews cite an incidence rate of 25-60% for patients developing further aneurysmal 
changes after aortic repair.  One center reported the rate of redo operations on TAAA repair to be 14%18.   
 
Aneurysms with Obstructive Stenting 
 
 
Patients suffering from thoracic and abdominal aortic aneurysms can benefit from the proven safety and 
efficacy of open surgical and endovascular stent grafting. However, the repair does not halt disease progression 
and may lead to future aneurysmal formation in adjacent segments of the aorta. The continued expansion 
necessitates revision to mitigate the risk of pending rupture. The incidence of revision following aneurysm 
repair is between 2.4-5.2%20 in abdominal aortic aneurysms and 14% in thoracoabdominal aortic aneurysms 
(TAAA)18. 
 
Treatment Options 
 
Medical Management 
 

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 Medical management of both fusiform thoracoabdominal aneurysms and type B aortic dissections 
includes normalizing blood pressure to prevent further dilation or dissection.  Close monitoring should be 
performed.  Operation should be limited to patients whose aneurysms are at least 5.5-cm in diameter, 
whose symptoms persist, whose aneurysms enlarge and are at least 4.5-cm in diameter, or who develop 
evidence of bleeding.  But if any of those conditions are observed (persistent symptoms, aneurysm 
enlargement, and evidence of bleeding), the patient should be offered repair.  For dissections operation is 
suggested for symptomatic patients and those with complications including malperfusion syndrome or 
active hemorrhage.  For prior repair, if there are persistent endoleaks, loss of seal, or device integrity issues 
of previously placed graft material repair should be offered. 
Open Surgical Repair 
Open repair of thoracoabdominal aneurysms, especially in patients with preexisting comorbidities, 
is fraught with complications. A meta-analysis of 7,833 open repairs of thoracoabdominal aneurysm repairs 
from 2000 to 2010 found a 30 day mortality rate of 7%, in-hospital mortality of 10%, spinal cord ischemia 
rates of 7.5%, renal failure rates of 19%, and pulmonary dysfunction rates of 36%21.  Predictors of adverse 
events after elective open repair based on pre-existing comorbidities have been established.  Advanced age 
(>70 years)22-25, respiratory disease24, renal insufficiency26, coronary artery disease22,25, symptomatic 
aneurysms, extent 1 and 2 aneurysms27-30, and diabetes31 are reported to be a predictor of 30-day mortality.  
Cardiac function32, extent 1 and 2 aneurysms28,33-35, symptomatic cases35, and diabetes31 are reported to be 
predictors of paraplegia.  The outcomes reported above are in a low- to moderate- risk patient population.  
It is a logical extension to assume the outcomes in moderate- to high- risk patients would be worse. 
 
Open Surgical Repair of Ruptured, Urgent, and Emergent TAAAs 
Open repair of any thoracoabdominal aneurysms, especially in patients with preexisting 
comorbidities, is fraught with complications. A recent review of emergent patients with a ruptured TAAA 
looked at the overall mortality of 51 emergently treated patients with TAAA between 1994 and 2014.  The 
study evaluated Crawford Type I, II, III, and IV presenting hemodynamically unstable (94%) and 
hemodynamically stable (3%).  In this study 54.9% (28/51) had true aneurysms and 45% (23/51) had 
dissecting aneurysms.  These were further broken into 94% (48/51) that presented emergently requiring 
treatment in 2-6 hours and 6% (3/51) that presented urgently and required treatment within 24 hours.  The 
overall mortality in this study was 43% (23/51); 15% (8/51) of these occurring during the procedure and 
27% (14/51) occurred post-operatively.  Of the 84% (43/51) that survived the initial procedure, 16% (6/42) 
developed paraplegia/paraparesis, 18.6% (8/43) had acute renal failure, 35% (15/43) had pulmonary 
insufficiency, and 18.6% (8/43) with post-operative bleeding.  The average visceral ischemic time was 36 
minutes and the average blood loss was 2875cc14.   
 
Open Surgical Repair of Chronic Type B Dissections 
Open repair of chronic type B dissections is known to have a higher mortality and morbidity rate.  A 
2014 review of open and endovascular outcomes for patients with chronic type B dissections cited an 
operative mortality of 6%, stroke rate of 16%, and paraplegia of 9%.  The one year major morbidity or 
mortality in these open repair patients was 25%36.   Another large study evaluating open repair results in 
1542 subjects reported a 30-day mortality of 17.8% 37.  One advantage of open repair compared to 
endovascular repair of type B dissections is a lower re-intervention rate36.   
Open Surgical Repair of TAAAs with prior repair  
 

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Open repair of any thoracoabdominal aneurysm, especially in patients with preexisting repair, is 
fraught with complications. The outcomes of redo open repair are typically worse compared to the index 
procedure.  If the open repair requires a redo left side thoracotomy this is associated with an increased risk 
of post-operative respiratory failure, longer operation time, and reduced long-term survival.  Additionally, 
if retroperitoneal redissection is required it increases the risk of major bleeding and damage to abdominal 
organs.  In a literature review of open repair of visceral aortic patch  aneurysms with reinclusion technique 
on the redo open procedure, centers reporting more than one case had a mortality rate ranging from 20-40% 
and a renal failure rate ranging from 0-50%19.  Another site evaluating 266 redo open TAAA repair 
procedures cited a 30-day mortality rate of 23%, post-operative coagulopathy 23%, stroke 6%, respiratory 
failure 44%, and renal failure 37%. The 5 year mortality was also determined to be 58.1% in redo patients, 
which is significantly higher than non-redo TAAA patients18.    
 
Open Surgical Repair of TAAAs with prior repair and obstructive stenting 
While revision with open surgical techniques can be an option in certain cases, the outcomes are 
poor in most patients given the advanced nature of their disease and associated comorbidities. 38,39  Given 
the extensiveness of these secondary repairs, most patients are either deemed not a surgical candidate or 
their repair is postponed longer than recommended by the Society of Vascular Surgeons.  Others have 
demonstrated the use of fenestrated and branched stent grafts to revise previous open and endovascular 
surgery.  40 
Endovascular Repair 
Parallel Grafts 
Parallel grafts (often referred to as snorkels, chimneys, periscopes, or CHIMPs) are combinations of 
aortic and branch stent grafts deployed simultaneously.  They are typically all straight-tube grafts where the 
open end is either on the proximal or distal extent (and sometimes both) of the aortic component.  The 
combination of straight tube stent grafts allows for the physician to treat emergent patients beings the 
assembly does not need to be custom made.  There are some criticisms though about the lack of 
circumferential seal and fixation though with parallel grafts.  This lack of circumferential seal and fixation 
may leave the patient vulnerable to endoleak. 
There have been case reports which describe two parallel stent graft techniques used to repair 
thoracoabdominal aneurysms.  The first ‘terrace technique’ has two chimney stents in contact with a more 
proximal thoracic graft and two chimney stents in contact with a more distal thoracic graft41.  The second 
has two chimney stents going to the celiac and superior mesenteric arteries.  Then there are two snorkel 
stents pulling retrograde flow and going to the renal arteries42-44.  
Snorkel and chimney grafts can be implanted with good technical success rates if care is taken, but 
long term renal function is in question.  Seal and fixation are also in question, so the parallel graft 
techniques should be avoided in elective settings and reserved for emergent settings45.  A recent review 
found that 10.7% of patients in the literature treated for thoracoabdominal aneurysm with parallel grafts 
experienced type 1 endoleak.  The investigator thought the approach would be useful for a recovery 
maneuver or for emergent cases where fenestrated grafts are not readily available, but long term durability 
and proximal fixation remain in question46.  
Sandwich Techniques 

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Two sandwich techniques have been proposed in order to care for patients with an off-the-shelf 
approach.  The first used dual bifurcated infrarenal grafts in the descending thoracic aorta47.  The second 
used 3-4 bridging stents sandwiched with a thoracic graft in the descending thoracic aorta48.  While these 
sandwich techniques can be used off-the-shelf, they do not provide for circumferential seal and fixation, 
and long term durability is in question. 
Fenestrated Stent Grafts 
While combinations of branched and fenestrated endografts can be specified and ordered from 
manufacturers to be customized for the patient in Europe, there are few studies of purely fenestrated 
endografts used in the repair of thoracoabdominal aneurysms.  A study showed the technique by which 
endografts can be modified in order to treat urgent cases of thoracoabdominal aneurysms49.  These authors 
recently published a case where this technique was used to repair a thoracoabdominal aneurysm in a 74 
year old male patient with very asymmetric visceral and renal vessels.  The repair was done by sewing 
Gore Viabahns to the fenestrations as ‘mini cuffs’ which helped to increase the amount of seal obtained.  
The patient had been followed for two months50.  Also a retrospective study in 2011 which reviewed the 
cases done in Paris, France and Cleveland, Ohio for type 4 thoracoabdominal aneurysms with custom 
manufactured fenestrated grafts was reported.  All patients were considered high risk for open repair.  Over 
a six year period, 231 patients were treated.  Thirty day mortality was 2.6% and 2 year survival was 83%.  
Freedom from secondary intervention was 93% at 30 days and 73% at 2 years51.   
Cook t-Branch Stent Grafts 
Branched stent grafts have been used for juxtarenal and pararenal aneurysms.  Modified branched 
stent grafts have only been reported to be used with thoracoabdominal aneurysms to date50,52.  There are no 
large scale studies of unibody axially-oriented multi-branched grafts for pararenal aneurysms as they are 
more frequently used for thoracoabdominal aneurysms.   
Branches have been attached to the aortic component to provide for bridging stent overlap, 
increased overlap encouraged seal and fixation.  It also allowed for the use of self-expanding stent grafts 
which help accommodate tortuosity.  Several variations of branch orientation exist including axial, helical, 
antegrade, and retrograde.  Axial branches were deployed proximal to the target vessels.  The branches 
were cannulated from an arm approach, and mating stents were deployed.  Bard Fluencies were commonly 
used and the length of overlap was typically 10-mm.  These were sometimes lined with balloon-expandable 
stents to prevent component separation.  Alignment between the axial branch stent and target vessel was 
noted as a problem if it caused angulation in the bridging stent, potentially leading to bridge stent kink.  To 
increase durability, self-expandable bare metal stents such as Boston Scientific Wallstents were 
occasionally used.  The helical branches exit the aortic component posteriorly and wrap around the main 
body.  The distal end landed 10-mm from the ostium of the target vessel.  The longer overlap and gentle 
sweeping centerline made lining the stents less critical.  The branch stent curved to become in-line with the 
target vessel.  The drawback was that the helical stents make for a bulky construct requiring a large 
diameter delivery system. 
Flow Diverting Devices 
Flow diverting stents are used in limited applications for repairing thoracoabdominal aortic 
aneurysms in Europe. They provide for more simplified implant in that the branch vessels do not need to be 
stented.  Instead the three layer micro-woven nitinol mesh significantly slows and alters the flow of blood 
into the aneurysm sac encouraging thrombus formation.  All the while, flow channels are developing to the 
branch vessels53-55.  The IFU must be followed very closely so that the stents do not overlap graft cloth, that 

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20-25% oversizing is followed, and so that larger stents are always deployed within smaller stents.  If these 
instructions are not followed, devastating ruptures may follow56-58.  Data is limited and largely 
retrospective in nature59.  The one registry reported had 380 patients but showed a technical success rate of 
0% when the IFU was not adhered to (n=38/38)60. 
 
Endovascular Repair of Ruptured, Urgent, and Emergent TAAAs 
There are no reports we found describing branched grafts being used for TAAA repair in a ruptured 
or emergent setting.  This is likely due to either manufacturer control of the use of the devices or control of 
the publication of information.  However there are several studies of parallel grafts being used in this 
setting.  A meta-analysis published revealed 15 reports of 93 such patients.  24.7% were operated on in an 
urgent setting, but the results were not compared to results of patients treated in a non-urgent setting.  
Because of this we cannot draw any conclusions46.    A further study examined parallel grafts used in 
ruptured thoracoabadominal aortic aneurysms and pararenal aneurysms used in 9 patients (6 
thoracoabadominal aortic aneurysms, 2 pararenal aortic aneurysms, and 1 short neck infrarenal aneurysm).  
The study mentions stable renal function in all patients and a very low 30-day mortality rate44.    Yet 
another study examined 29 patients treated with the parallel graft technique of these14 patients were 
ruptures and 15 patients were symptomatic.  Nine lesions were in the aortic arch, ten were in the 
descending aorta, and ten were in the branched visceral segment.  Twenty two were treated in the first 24 
hours and 7 were treated in the first 3 days.  Median follow-up was 2 years.  There were four 30 day deaths 
(1 cerebral infarct, 1 visceral ischemia, 1 multiple organ failure, and 1 heart failure).  The authors remarked 
that this technique is promising with low rates of early mortality when considering that the patients were 
emergent61.  Three additional cases were reported but the cases focused mainly on technical feasibility and 
endoleaks, as a means of demonstrating the technique with little focus on the clinical sequelae that may 
develop during urgent repair of thoracoabadominal aortic aneurysms with endovascular techniques62-64.    
From this limited data set coupled with our current understanding of the outcomes of patients treated with 
open repair in the urgent setting, it appears that the benefit of endovascular repair may outweigh the risks.   
 
Endovascular Repair of Chronic Type B Dissections 
Incidence rates of aortic dissection is estimated to be roughly 3 per 100,000 people per year65,66.  
Until recently acute Stanford type B aortic dissections were managed with blood pressure control67,68.  If 
endovascular intervention is offered in acute dissections the goal is typically to cover the proximal entry 
tear in order to block antegrade flow to the false lumen. This starts the process of aortic remodeling by 
depressurizing the false lumen69.  If only the thoracic aorta is to be treated, growth of the true lumen and 
shrinking of the false lumen are generally not associated with distal reperfusion or endoleak – meaning 
there is a lower rate of reintervention70.   As endovascular repair is becoming more prevalent, we are 
learning that chronic dissections tend to have a thicker fixed septum which leaves the aorta less susceptible 
to remodeling after repair71.  Therefore, treating acute Type B dissections with blood pressure management 
may not be the best approach, because if endovascular repair is needed later the process of remodeling may 
not happen.  If the aneurysm and dissection extend distally beyond the diaphragm, the types of 
fenestrations that are found in extensive Stanford type B dissections leave the patient prone to distal 
reperfusion of the false lumen even after cover of the proximal entry tear 72,73.  These patients will require 
some sort of branched or fenestrated repair.  If the patient has an aneurysm complicated by type B 
dissection where visceral branches arise from both true and false lumen the treatment options are even 
further limited, and bridging stents will have to cross the septum increasing the technical difficulty of 
completing the case.  Small true lumens and visceral arteries arising from either true- or false- lumen and 
dissection extending to branches have made endovascular repair sometimes near impossible.   

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Endovascular Repair of TAAAs with prior aortic repair  
The risk of increased mortality and complications in redo open TAAA repair suggest that a less invasive 
approach such as endovascular repair is warranted.  Numerous single site articles have been published 
regarding branched or fenestrated aneurysm repair following a prior aortic repair.  The prior repairs 
documented include endoluminal abdominal aortic aneurysm repair, aorto-bifemoral bypass, and open 
repair with a tube prosthesis for post-operative complications including Type I endoleak, suprarenal 
extension of the aneurysm, and anastamotic aneurysms 20.  The most common risks and complications 
documented in the endovascular repair of a previous intervention include Type III endoleaks at the modular 
joint and the increased graft on graft friction making graft maneuverability and repositioning difficult.  
Despite the risks, it was determined that the option of endovascular repair may be advantageous to this 
group of patients with a history of multiple abdominal operations or with serious cardiopulmonary risk 
factors as compared with the more invasive open surgical repair74.   
Endovascular Repair of TAAAs with prior repair and obstructive stenting 
While revision with open surgical techniques can be an option in certain cases, the outcomes are poor in 
most patients given the advanced nature of their disease and associated comorbidities. 38,39  Given the 
extensiveness of these secondary repairs, most patients are either deemed not a surgical candidate or their 
repair is postponed longer than recommended by the Society of Vascular Surgeons.  Others have 
demonstrated the use of fenestrated and branched stent grafts to revise previous open and endovascular 
surgery.  40 
Staged Endovascular Repair 
Planned Staged Procedures 
Staged procedures have been used in endovascular repair of thoracoabdominal aortic aneurysms in an effort 
to limit the incident and severity of spinal cord ischemia.  The hypothesis behind this is the staging of 
procedures allows for the development of a collateral network.  The collaterals would maintain some 
perfusion and allow other vessels to compensate reducing the overall impact of spinal cord ischemia.  One 
center studying 87 Type II subjects found that staging reduced the overall SCI rates significantly 57.75.  The 
SCI rate in single stage procedures was 37.5% (12/32) and 11% (3/27) in two-stage procedures.   The rate 
was slightly higher in unintentionally staged procedures at 14% (4/28).  Unintentional staging was defined 
as prior aortic repair, 21% (6/28) had prior thoracic repair and the remainder were abdominal aortic repair.  
In the staged procedures, the two-stage repair SCI events were all temporary and resolved by discharge and 
the unintentional staging had 10% (3/28) that resulted in permanent SCI.  This study had a median time 
between stages of 5 months (range 1-60 months), but the investigators believe 2-3 weeks to be 
optimum57.optimum75.  The investigators also noted that symptomatic patients should be monitored and 
considered for earlier repair.  While there is no specific length of aortic coverage to determine the threshold 
where one should consider staging, this study cites that aortic coverage of 200 cm or greater may indicate 
the threshold where subjects would benefit from staging.   
There are several techniques used for staging endovascular TAAA repair.  Techniques include coverage of 
the proximal thoracic aorta up to the celiac artery in a staged procedure with visceral stenting performed at 
the completion procedure.  Other techniques reference placing the main aortic stents, but allowing 
perfusion from an open celiac branch, perfusion branches, or unstented contralateral iliac limb58.limb76.  
The use of perfusion branches may be preferred to allow for better hemodynamics and avoid excessive 
pressurization of the aneurysm sac.   

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Bail-out Staged Procedures 
 
There is limited information available on use of staging as a bail-out procedures.  Several sites and 
investigators discuss alternative techniques such as chimney and snorkels as alternative techniques to be 
used in technically challenging cases complicated by anatomy59anatomy77, but fail to reference the use of 
staging and outcomes.  Literature also cites several intra-operative techniques for bail-out maneuvers in the 
operating room60room78, but currently available TAAA technologies do not allow for staging of the aortic 
components and limited data is available on the outcomes of these cases.   
Summary of Alternative Treatments 
A few endovascular options are available for treating thoracoabdominal aneurysms.  A limited 
number of centers have access to commercially available branch-fenestrated devices, but they typically 
require customization.  This customization has an associated lead time of several weeks.  The endovascular 
options present a real problem of patients not being able to either travel to the select sites or being emergent 
and not having the time to wait for a custom graft.  In these instances it may appropriate for the patients to 
be treated either with off-label devices (sandwich approach) or with physician-modified endografts.   
Sandwich configurations tend to have excellent patency rates but lack circumferential seal and fixation.  
Branch-fenestrated grafts have good seal and fixation but tend to have high frequency of reintervention and 
can be limited by patient anatomy.  In all instances careful case planning is in order and all aspects of 
parallel grafts as well as branch-fenestrated grafts should be carefully considered relative to individual 
patient anatomy. 
Summary of Treatments for Staged Procedure or Staged Bail-out Procedure 
Due to the proximal seal zone of this device, several options are available to stage patients with 
either a planned procedure or as a bail-out procedure.  Literature supports the hypothesis that a controlled 
endoleak or perfusion branch can be protective for SCI events by helping create a protective collateral 
network.  When planned visceral artery bridge endoleak can be provided via a low-risk staged procedure 
that does not put the patient at significant risk from the intervention.  The use and experience with staged 
procedures as a bail-out method is not widely understood, but still allows the patient to maintain perfusion 
to the visceral vessels and lower extremities while they recover and prepare for completion of the 
procedure.  The bail-out staging method is only intended to be used in extreme circumstances when patient 
status declines intraoperatively or unforeseen technical challenges are encountered.   
Benefits and Risks of Treatment Options 
Open Surgical Repair 
Contemporary series have shown that open repair of thoracoabdominal aneurysms, is associated 
with a significant mortality risk and increase in major complications. One report describes 7,833 open 
TAAA repairs from 2000 to 2010 found a 30 day mortality rate of 7%, in-hospital mortality of 10%, spinal 
cord ischemia rates of 7.5%, renal failure rates of 19%, and pulmonary dysfunction rates of 36%21.  The 
risks of open repair are significantly higher than any other option for repair.  Open repairs are durable but 
have substantial perioperative mortality and postoperative morbidity.  Additionally, due to existing 
comorbidities and the high risk for complications this is not an option for many patients.   
Endovascular Techniques 
There is limited availability of data reporting the results of endovascular repair of thoracoabdominal 
aneurysms.  Many of these techniques require off-label use or modification of the grafts, which bring into 

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question the safety and long-term durability. The literature suggests that snorkel and chimney grafts can be 
performed with decent technical success rates, but seal and fixation and long term durability are in question 
and have not been formally evaluated45.  A recent review found that 10.7% of patients in the literature 
treated for thoracoabdominal aneurysm with parallel grafts experienced type 1 endoleak.   
A 2004 to 2006 study of the novel t-branch device (Cook Medical) was studied in high risk 
subjects.  The study showed a technical success of 93%, thirty-day mortality of 5.5%, major perioperative 
complications 14% including paraplegia 2.7%, new onset dialysis 1.4%, respiratory failure 6.8%, 
myocardial infarction 5.5%, and stroke 1.4%.  All-cause mortality at twelve months was 6 subjects.  There 
was no evidence of stent migration or aneurysm growth over the twelve month period75.79.     
In a study of type 4 thoracoabdominal aneurysms with custom manufactured fenestrated grafts over 
a six year period, 231 patients were treated.  Thirty day mortality was 2.6% and 2 year survival was 83%.  
Freedom from secondary intervention was 93% at 30 days and 73% at 2 years51.   
Experience with the t-branch device evaluating 22 patients between 2010 and 2013 reported a 
technical success of 100%.  The re-intervention rate at 6 months was 90%, branch occlusion was 14%, 
paraplegia was 5%, and paraparesis in 5%.  Again, these lack long-term data to address the durability of the 
stent grafts.  In all endovascular options, close surveillance is mandatory for early identification of visceral 
or branched vessel stenosis or pre-occlusion.   
A retrospective study reported by Sanford Health (IDE Application G140207, Clinical Use 
Summary) reports the only subjects that would not be ideal candidates include subjects with prior 
suprarenal fixation stents, dissection, present emergently.  The retrospective study examines 12 patients 
which meet the clinical study criteria that were treated between 2012 and 2014.  In this patient population, 
there was one subject with renal failure and one subject with a respiratory event in the first 30 days.  There 
was one unrelated patient death and one CVA in the first year.  Additionally, in this study there was one 
instance of branch vessel occlusion and secondary intervention.   
A large number of subjects may benefit from alternative endovascular treatments that may be 
performed with less risk of complications and shorter recovery time.  For these subjects, endovascular 
repair with a manifold system that is not based on patient anatomy may be the only treatment option.   
Proximal Extension 
 The overlapping or layering of Valiant stent grafts has been a standard practice in clinical care of 
subjects with thoracic aortic disease.  Data reported by Sanford Health (IDE Application G140207/S034, 
Clinical Use Summary) include 23 patients treated between 2012 and 2017 using a combination of the 
Valiant stent graft with the Thoracic Bifurcation no evidence of migration.  There were three 
reinterventions (3/23, 13%)  including one for a dissection distal to the thoracic graft and two for 
endoleaks.  There has been a follow-up of over 5 years supporting the safety of this device when layered to 
extend the proximal landing zone of the thoracic bifurcation. The one year survival of a non-emergent TAA 
is 82% at one year76The one year survival of a non-emergent TAA is 82% at one year80 and 55.8% at 5 
years77.81. This proximal extension is done in two layers to mitigate the risks of material fatigue and wear. 
Either Valiant Captivia or Valiant Navion may be used as a proximal extension. 
 
Staged Procedures 

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With the Valiant Thoracoabdominal Stent Graft System, the risks of planned staging via the visceral artery 
bridge endoleak are comparable to the single stage procedure in the current protocol. We do not believe 
staging presents any new risks that are not currently covered under the risk profile for the VTAAA system, 
but these risks may happen at a higher frequency.  These risks still present no greater risk than the probable 
risk from the progression of the patient’s condition.  The increased risks for a planned stage procedure 
(visceral artery bridge endoleak or delayed distal seal) are risks from an additional procedure including 
anesthetic and contrast exposure, compounded physiologic insult from multiples procedures, access site 
complications, wire injury, device integrity issues from component interaction, paraplegia, spinal cord 
ischemic event, aneurysm enlargement, aneurysm rupture, and death.  Increased risks for a bail-out staged 
procedure include the above risks and increased procedure time or failure to treat.    
Stent graft designs 
 
The manifold system has the advantage of being independent of patient anatomy allowing for use 
off-the-shelf.  It can also adapt to numerous anatomical variations including tortuosity and vessel location.  
The design allows for continuous flow to the visceral and infrarenal segments throughout the procedure.  
Additionally, the proximal deployment and delayed distal seal allows for more flexibility in stenting the 
visceral vessels, multiple bail outs, or staging of the procedure throughout device deployment.  The 
importance of proximal deployment and gradual sweeping branch stents has been reported as a critical 
element for maintaining vessel patency82.   
Analysis of bridging stent characteristics 
 It has become evident that the use of the appropriate bridging stent including placement and stent 
is necessary to minimize risk of target vessel occlusion and kinking82.  The ideal stent has not been 
determined or standardized, but currently a balloon expandable stent covered is preferred.  The use of a 
covered stent has the advantages of optimal seal, minimizing risk of endoleak, and improved patency 
rates83.  The two most widely used stents are the iCAST covered stent (Atrium Medical) and the JoMed 
stent (Abbott).  The iCAST covered stent has been widely used and reported in the literature, and was the 
most frequently used stent in the recent GLOBALSTAR registry, with only five of 889 visceral arteries lost 
during follow up84.  The JoMed stent has been also widely used and it is the balloon expandable covered 
stent of choice by the Cleveland Clinic group, with recent report of >95% 5-year visceral artery patency 
among 632 subjects treated by fenestrated endografts85.  The long-term risks of stent fracture and 
dislodgment have not been systematically reported but seem to be exceptionally low with adequate 
selection of proximal landing zone.  The Fluency stent (Bard Peripheral Vascular, Tempe, AZ) has been 
used by one investigator, with excellent patency rates and low risk of kinking or stent fracture86. 
Justification for Specific Patient Selection Criteria Relevant for this Study   
Treatment of TAAA aneurysms in all patients that meet entry criteria will be considered for this 
study.  All patients diagnosed with a TAAA repair are considered high risk due to the natural history of a 
patient with a TAAA.  Their options are limited for endovascular repair and due to the comorbidities in this 
population they are all high risk open repair.  Additionally, all patients undergoing open surgical repair of a 
thoracoabdominal aneurysm are considered to be at high risk for comorbidities and complications.  Based 
on initial clinical experience, we believe that we can treat all patients with outcomes better to those of open 
surgical repair with less cost over the year.  The current approach is an endovascular repair with lower 
surgical morbidity and mortality rate compared to open repair.  Endovascular repair may also decrease the 
recovery time and length of hospital stay.  From the initial clinical evaluation, certain patients may not be a 
good candidate for this approach have been identified.  This patient population includes patients presenting 
emergently, with compromised renal access, or dissections.  The inclusion and exclusion criteria for this 
study has been refined to present a patient population that we feel may significantly benefit from this 

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procedure without undue risk.  The inclusion criteria listed in section 6 including aneurysm characteristics, 
access vessel morphology, minimum neck length, diameter of aneurysm, branch vessel size, patency of the 
four major visceral vessels, and size of distal fixation site are required as inclusion criteria to achieve an 
adequate seal zone and optimal placement with the stent graft and branches.   
The patient population being excluded from this study includes patients with a ruptured aneurysm 
(or contained rupture), obstructive stenting of the visceral vessels, or a dissection in the treated portion of 
the aorta.  Also patients with thrombus or excessive calcification within the neck of the aneurysm will be 
excluded as they put the patient at high risk of aneurysmal rupture or embolic event during surgical 
manipulation.  Anatomy that does not allow for primary or assisted patency of the left subclavian artery 
will be excluded because it is required for access.  Additionally, anatomy that would not allow for 
maintenance of at least one patent hypogastric artery will be excluded in order to prevent organ and/or 
pelvic ischemia and paraplegia.     
 
In reference to the objective of cost of TAAA delivery, prior studies suggest the one-year costs 
associated with open TAA repairs are approximately $150,000+/-$10,000. 56Assuming a power of 80% and 
alpha=0.05, we would need 20 patients per group to detect a difference of $20,000 between the mean one-
year costs of open TAA repair vs TEVAR.  Longitudinal costs over a one year period, inclusive of global 
healthcare costs (readmission, outpatient care, rehabilitation stays) are not available from the literature, but 
would be analyzed in this study, and thus inform healthcare policy, reimbursement strategies, and hospital 
administrators. 
 
 
 
Cost allocation for Open Thoracic Aortic Surgery (left) versus Thoracic Endovascular Surgery (right).  
Total cost for open surgery $64,531 vs. 61,909 for endovascular surgery (p=0.4) 
 
 
There are significant differences in the cost allocations to deliver open surgery versus endovascular TAAA 
repair, with device charges being central drivers to cost for endovascular TAAA repair and bed charges 
related to long hospitalization driving cost for open surgery.57 These costs allocations yield a similar 
hospitalization cost, yet don’t account for substantive differences in post-hospital disposition, wherein 
further costs may be rapidly accrued by need for subacute or rehabilitation facility more often with open 
surgery. This study will capture such critical information and inform payor structure. 
 
Rationale for Exposing Target Population to Potential Risks of Staging 

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The planned staged method via the visceral artery bridge endoleak and delayed distal seal has been used 
successfully in 6 cases under PS-IDEs G170048 and G170024; 4 patients had their aneurysm successfully 
excluded (3 via the visceral artery bridge endoleak and 1 via delayed distal seal) in a staged fashion with 2 
patients awaiting completion (1 via the visceral artery bridge endoleak and 1 via delayed distal seal). (Dr. 
Murray Shames, IDE G170024 and Dr. Thomas Maldonado, IDE G170048).   There were no intra-
operative deaths or SCI events, supporting that the device when used in planned staged procedure can be 
implanted safely and repeatedly.  When compared to literature reported SCI rates for single stage TAAA 
procedures, this is a viable option for patients at higher risk for SCI events.  Given the success we have 
experienced with patients treated to date and the low risk of the completion procedure, we feel that it is 
justified to expose the target patient population to the potential risk.   
Device Description and Drawings 
The Valiant Thoracoabdominal Stent Graft System is made up of two main body components and 
makes use of several off-the-shelf FDA-approved stent graft components (see Appendix B for system 
drawing).  The two custom main body grafts are the thoracic bifurcation (Figure 1A) and the visceral 
manifold (Figure 1B).  The thoracic bifurcation is deployed in the thoracic aorta and provides the proximal 
seal for the device.  For a Type I or II thoracoabdominal aneurysm the proximal seal is in zone 3, for Type 
III and V the device seals in zone 4.  The two limbs of the thoracic bifurcation allows for continued aortic 
flow while deploying the visceral segment.  The visceral manifold is deployed within the larger 20 mm 
limb of the thoracic bifurcation to set the stage for the visceral debranching.  The branches of the visceral 
manifold extend to the visceral vessel with the use of covered bridging stents and provide distal seal of the 
manifold.   The smaller 16 mm limb of the thoracic bifurcation extends to the infrarenal segment to either 
seal in zone 9 for a Type I and V and in zone 10 for Type II and III.  All other connections in the device 
make use of sizes that are modular and independent of patient anatomy. 
Figure 1: Valiant Thoracoabdominal Stent Graft System 
 
A 
B 
Figure 1: Images of the manufactured device A) the thoracic bifurcation main 
body graft and B) visceral manifold main body graft 
Aortic components 
The thoracic bifurcation stent graft (Medtronic) seals to the native aorta/healthy tissue/prior surgical 
graft and bifurcates blood flow in the descending thoracic aorta.  The distal end bifurcates into two smaller 

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legs (20 mm and 16 mm) suitable for modular connection to the visceral manifold stent graft and the 
visceral bypass stent graft.  The thoracic bifurcation is composed of a self-expanding, metallic spring 
scaffold made from nitinol stents sewn to a polyester fabric graft with nonresorbable sutures and is 
manufactured in the following sizes:  
 
 
Table 2.  Thoracic bifurcation dimensions 
 
The proximal end of the visceral manifold stent graft (Medtronic) deploys into the 20 mm leg of the 
thoracic bifurcation and quadfurcates to perfuse the celiac, SMA, right, and left renal arteries via bridging 
stents.  The visceral manifold is composed of a self-expanding, metallic spring scaffold made from nitinol 
stents sewn to a polyester fabric graft with nonresorbable sutures and is manufactured in the following 
sizes: 
Table 3.  
Visceral manifold dimensions 
Branch components 
 
The limbs of the visceral manifold are extended to the target branch vessel with 9-mm balloon 
expandable stents (Atrium, iCast).  The Atrium iCasts are a stainless steel stent covered with a PTFE film 
and these are not modified by the physician.  The balloon expandable stents are overlapped to reach the 
target branch vessel and the distal end is appropriately sized to the branch vessel.  The interfaces between 
the branch components are lined with self-expanding bare metal nitinol stents (Medtronic, Complete SE) to 
improve resistance to kinking and stent graft separation.   
Iliac extension components 
The visceral bypass (Medtronic) deploys into the 16 mm limb of the thoracic bifurcation to perfuse 
the iliac segment.  The visceral bypass is composed of a self-expanding, metallic spring scaffold made from 
nitinol stents sewn to a polyester fabric graft with nonresorbable sutures and is manufactured in the 
following sizes: 

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Table 4.  Visceral bypass dimensions 
 
The infrarenal bifurcation (Medtronic) deploys into the visceral bypass to bifurcate aortic flow to 
the iliac segments.  The infrarenal bifurcation is composed of a self-expanding, metallic spring scaffold 
made from nitinol stents sewn to a polyester fabric graft with nonresorbable sutures and is manufactured in 
the following sizes: 
 
Table 5. Infrarenal bifurcation dimensions 
 
 
The iliac limbs and extenders (Medtronic, Endurant II) will be utilized from a commercially 
available Endurant II limb or appropriately sized iliac limb extension stent graft.  These will be deployed in 
the infrarenal bifurcation and will provide distal seal of the stent graft system.  The iliac limbs will be 
available in the commercially manufactured sizes and appropriately oversized for implantation in the 
infrarenal bifurcation.   
Principles of Operation 
The Valiant Thoracoabdominal Stent Graft System works to bifurcate aortic flow upstream of the 
target visceral vessels.  This bifurcation has a two-fold benefit.  First it allows for aortic flow to be 
compartmentalized into a visceral segment and an infrarenal segment providing for uninterrupted flow to 
the visceral vessels as well as the infrarenal segment throughout the procedure.  If any of the connections 
cannot be made or the patient status declines during the procedure, then it can be staged and the 
connections can be made at a later date.  Second, the upstream bifurcation encourages more favorable flow 
conditions in the bridging stents and target vessels which may prevent target vessel occlusion.  This is due 
to the fact that the bifurcations are upstream providing a sweeping transition into the renal arteries that is 
smooth providing for relatively laminar flow conditions.  The design demonstrates that more central aortic 
flow is obtained with this design increasing flow rates in the visceral vessels to potentially increase target 
vessel patency (Figure 2). 
The device can be used as an off-the-shelf system, negating the need for lead times associated with 
custom-built devices.  The critical sizing that will need to be done is with the proximal end of the thoracic 
bifurcation, distal landing zone in the aorta or iliac arteries, and the bridging stents.  The proximal end of 
the thoracic bifurcation can be sized by choosing any of the available sizes of the Medtronic TAAA 
thoracic bifurcation stent grafts, and the sizes of the bridging stents can be manipulated by choosing any of 
the commercially available sizes of the Atrium iCast.  The Atrium iCasts are added to the system in-vivo 
and connected with passive fixation which negates the need to size the main body components based on the 

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target vessel sizes.  All other connections in the device make use of sizes that are the same, independent of 
patient anatomy. 
The deployment of this device is also independent of device alignment.  Angular alignment of the 
thoracic bifurcation and the visceral manifold has very little impact on the outcome of the case.  
Longitudinal alignment is more important, but a safety factor has been built-in by calling for the distal ends 
of the visceral manifold to be deployed above their target vessels by 1-2 cm.  The longitudinal landing 
should be optimized so that the graft is not landed too low so that the connection with the visceral vessels is 
challenging to make. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intended Use/Indications for Use 
The Valiant Thoracoabdominal Stent Graft System is indicated for the endovascular treatment of 
thoracoabdominal aortic aneurysm (Crawford Type 1, 2, 3 and5) in patients with the following 
characteristics: 
• An aneurysm with a maximum diameter of > 5.5 cm or 2 times the normal diameter just proximal to 
the aneurysm using orthogonal (i.e., perpendicular to the centerline) measurements 
• Aneurysm with a history of growth  > 0.5 cm in 6 months 
• Saccular aneurysm deemed at significant risk for rupture 
• Symptomatic aneurysm greater than or equal to 4.5 cm 
• Axillary or brachial and iliac or femoral access vessel morphology that is compatible with vascular 
access techniques, devices or accessories, with or without use of a surgical conduit 
o Proximal landing zone for the thoracic bifurcation stent graft that has: 
Figure 2: Assembly drawing showing the thoracic bifurcation, the 
visceral manifold, the branch stents, and the infrarenal grafts, all 
deployed within an idealized aneurysm sketch. 

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• 
≥ 2.5 cm of healthy/nondiseased tissue including both native tissue and previously 
placed graft, (neck) distal to the left subclavian artery (LSA) with a diameter in the range 
of 26-42 mm 
• 
Adequate distance from the celiac artery, in order to accommodate cannulation from the 
antegrade access point when considering the total deployed length of the thoracic 
bifurcation and visceral manifold 
• Iliac artery or aortic distal fixation site, including both native tissue and previously placed graft, 
greater than or equal to 15 mm in length and diameter in the range of 8 – 25 mm 
• Age: ≥ 18 years old 
• Life expectancy: > 1 year 
 
Reference to Regulatory Submissions for Nonclinical Testing Information 
This device is currently under clinical investigation in the United States under IDE #G140207.  The 
proposed device is manufactured and tested by Medtronic.  Non-clinical data to support the investigational 
device is listed in the Medtronic Valiant Thoracoabdominal Stent Graft System Master File, MAF-2551.   
Summary of Nonclinical Information to Support Study Initiation 
All non-clinical testing to support the manufactured device was performed by Medtronic and is 
reported in the Valiant Thoracoabdominal Stent Graft System Master File, MAF-2551.   
Rationale for the Selection of Tests 
The rationale for the selection of tests is described in a device evaluation strategy table describing 
the Valiant Thoracoabdominal Stent Graft System as a whole.  This device evaluation strategy table 
describes the device procedure, performance, and basic safety-related attributes and addresses the potential 
failure modes and subsequent clinical mitigation strategies for the proposed investigational device.  This is 
attached in Appendices.  
Report of Prior Investigations Synopsis 
The outcomes from prior clinical evaluation of the study device, including successfully treating 
99% (84/85) of the intended target vessels and 96% (27/28) limb patency observed at one year, demonstrate 
the potential benefits of the device.  When contrasted with open repair’s significant complication rates and 
branch fenestrated device’s significant anatomic and logistic limitations, the potential risk of the proposed 
novel graft does not outweigh the potential benefit of widened anatomic availability and improved patency 
rates.  Given the potential benefits, we feel that it is justified to expose the target patient population to the 
potential risk.  The non-clinical testing performed by Medtronic and the clinical results reported by Sanford 
Health show adequate safety of the device to support a durable comparison of longitudinal cost and patient 
centered outcomes for patients treated with the Medtronic Valiant Thoracoabdominal Stent Graft System, 
and provide a valid comparison of open and endovascular surgical outcomes for TAAA patients.   

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4. 
Study Procedures 
 
a. Study design, including the sequence and timing of study procedures   
(distinguish research procedures from those that are part of routine care). 
 
Patient Population 
The study will evaluate 16 patients with type I, II, III, and V thoracoabdominal aneurysms 
meeting protocol inclusion criteria.  The patient population includes both male and female 
patients greater than 18 years old with a life expectancy of at least one year.   
 
Study Type and Duration 
This study is a prospective, single-center, non-randomized, multi-arm study to evaluate the 
therapeutic benefit of the Valiant Thoracoabdominal Stent Graft System.  A total of 16 patients 
(10 in the primary ptudy arm; 6 in the expanded selection criteria arm) will be enrolled in the 
study for treatment with the Valiant Thoracoabdominal Stent Graft System.  The duration of the 
Investigation is anticipated as follows: 
• 
Time to Complete Enrollment: 24 months 
• 
Subject Follow-up Time: 5 years from last subject enrollment 
• 
Total Duration Time: 7 years 
 
Intended Use 
The Valiant Thoracoabdominal Stent Graft System is indicated for the endovascular treatment 
of thoracoabdominal aortic aneurysm (Crawford Type 1, 2, 3 and 5) in patients with the 
following characteristics: 
o An aneurysm with a maximum diameter of  > 5.5 cm or 2 times the normal diameter just 
proximal to the aneurysm using orthogonal (i.e., perpendicular to the centerline) measurements 
o Aneurysm with a history of growth >  0.5 cm in 6 months  
o Saccular aneurysm deemed at significant risk for rupture 
o Symptomatic aneurysm greater than or equal to 4.5 cm 
o Axillary or brachial and iliac or femoral access vessel morphology that is compatible with 
vascular access techniques, devices or accessories, with or without use of a surgical conduit 
o Proximal landing zone for the thoracic bifurcation stent graft that has: 
• ≥ 2.5 cm of healthy/non-diseased tissue including both native tissue and previously 
placed graft, (neck) distal to the left subclavian artery (LSA) diameter in the range of 
26-42 mm 
• Adequate distance from the celiac artery, in order to accommodate cannulation from 
the antegrade access point when considering the total deployed length of the thoracic 
bifurcation and visceral manifold 
o o 
Iliac artery or aortic distal fixation site, including both native tissue and previously 
placed graft, greater than or equal to 15 mm in length and diameter in the range of 8 – 25 mm 
o Age: ≥ 18 years old 
o Life expectancy: > 1 year 
 
Patient Enrollment and Screening 
The investigator will assess potential study subjects with thoracoabdominal aortic 
aneurysms for their suitability for enrollment into the clinical study.  If the patient appears to meet 
eligibility criteria, either for the primary study arm or the expanded selection arm, then the 
investigator or clinical study coordinator will discuss the study with the patient and provide patient 
education materials to adequately inform the patient of potential risks and benefits, required follow-
up procedures, and answer any questions.  The clinical study coordinator will facilitate the informed 

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consent process.  After the patient has been properly consented, the patient will complete additional 
screening procedures that need to be completed.  If the patient does not sign the informed consent, 
they will not be enrolled in the study.  Information to be collected for screening includes: 
 
o Patient demographics 
o Medical history 
o Current health status 
o Physical examination 
o Ankle Brachial Index (ABI) 
o Pregnancy test (for female patients of childbearing age) 
o CTA or CT with contrast of the chest, abdomen and pelvis if renal function allows.  If renal 
function does not allow CT with contrast, an alternative contrast-enhanced imaging modality or, at a 
minimum, CT non-contrast in conjunction with Duplex ultrasound will be used at physician 
discretion to evaluate: 
• Access vessels for compatibility with vascular access techniques 
• Obstructive stenting of the visceral vessels 
• Vessels diameters suitable for use with the Valiant Thoracoabdominal Stent Graft System 
• Aneurysm rupture 
• Dissection 
• Patency of left subclavian artery, hypogastric arteries, lumbar arteries, and all four visceral 
vessels 
• Thrombus or excessive calcification in the neck of the aneurysm 
• Presence and location of any previously placed graft material 
o Complete blood count to evaluate white blood cells, hemoglobin, and platelets 
o Basic metabolic panel to evaluate creatinine 
o For patients with a history of smoking a pulmonary function test  
o Cardiac clearance 
Case Planning 
From the pre-op CT, the surgeon will make the following measurements to size the endografts. 
1. Length of the proximal seal zone, the distance required to land the thoracic bifurcation stent 
graft, this requires ≥ 2.5 cm section of healthy aorta or previously placed graft material, distal to 
the left subclavian artery or ≥ 2.5cm of surgical graft.   
2. Diameter of the proximal landing zone to define the required diameter of the thoracic 
bifurcation stent graft.  The diameter of the thoracic bifurcation stent graft should be 10-15% 
larger than the diameter of the aorta to proper oversize the stent graft.   
3. Maximum aortic diameter within the treated aorta 
4. Distance from the top of the celiac to the top of the most cephalic renal.   
5. Distance from the top of the proximal seal zone to the takeoff of the celiac.   
6. Distance from the top of the celiac to the SMA.   
7. Angulation at the mid-thoracic aorta. 
8. Angulation at the diaphragm. 
9. Angulation at the renal arteries. 
10. Distance from the right renal to the ispilateral internal iliac artery. 
11. Distance from lower renals to aortic bifurcation.    
12. Diameter of the branch vessels (celiac, SMA, left renal, and right renal) to determine the 
diameter bridging stents needed and percent patency.   
13. Diameter of the right and left common iliac to secure the distal seal of the infrarenal bifurcation.   
14. Diameter of the distal aorta to secure the distal seal in aorta 

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15. Minimum diameter of the access sites (right and left femoral and brachial access site).   
16. Length from the access sites to the target treatment zone (right and left femoral and brachial 
access site).   
17. Length between distal edge of LSA and start of aneurysm 
18. Length of proximal seal zone 
19. Length of aneurysm 
Note: If treating a dissection under the expanded selection arm the true and false lumen as well as any 
naturally occurring fenestrations will be evaluated to determine placement of the device and which lumen 
feeds the branch vessels.   
Note: If treating a patient with previously placed graft material, either proximally or distally, it must be 
determined if the landing zones will be within the previously placed graft material or if it the landing zones 
extend beyond the limits of the previously placed graft material. 
Pre-operative procedures 
The patient will be removed from anti-coagulants prior to surgery.  The day of surgery the 
following labs will be taken: 
o Complete blood count to evaluate white blood cells, hemoglobin, and platelets 
o Basic metabolic panel to evaluate creatinine 
o Prothrombin time (at physician discretion) 
o Partial thromboplastin time (at physician discretion) 
o Pregnancy test (for female patients of childbearing age) 
The patient will be treated with general anesthesia under standard medical practices along with 
placement of a lumbar drain when possible.  The management of anesthesia and the lumbar drain will be 
performed by the staffed anesthesia team.  Standard heparinization practices will be followed and active 
clotting time will be monitored throughout the procedure.  The patient will be prepped in normal sterile 
fashion from the clavicle to mid-thigh.  Additionally contrast will be diluted 50/50 in saline to reduce 
contrast exposure.  Radiation reduction procedures will be followed as allowed.   
 
Thoracic Grafts as a method of staging. 
Use of thoracic grafts as a method of staging as a pre-operative adjunct procedure. 
a. Thoracic Graft Placement 
i. This refers to implanting stent-grafts into the thoracic aorta prior to enrollment into 
the IDE clinical study.  
ii. Device Visualization and Preparation 
Refer to the Instructions for use provided for the thoracic components to be used.   
iii. Device Placement 
Ensure that the distal edge of the thoracic graft is 5-7 cm proximal to the celiac artery. 
iv. Thoracic Aorta Component Deployment 
Follow the study protocol or IFU for deploying the thoracic graft components. 
v. Completion  
The date of the index procedure will be targeted for within 6 weeks of the thoracic graft placement, 
but will be based on physician discretion, clinical presentation, and patient compliance.   
 
Implant Procedures 
Note: The design of the Valiant Thoracoabdominal Stent Graft System is modular in nature and 
allows for bailouts and staging of the procedure following the deployment of each device.  The procedure 
can be stopped at the completion of deployment of each component of the system and the patient has the 
opportunity for alternate endovascular, open repair techniques, or completion of the procedure at a later 
date if such conditions arise.   

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A. The implantation of the Valiant Thoracoabdominal Stent Graft System is conducted under 
fluoroscopic/angiographic guidance.  Refer to the Medtronic Valiant Thoracoabdominal Stent Graft 
System Instructions for Use (IFU) for techniques and methods for device deployment and 
implantation.   
B. The Valiant Thoracoabdominal Stent Graft System may be implanted in a staged procedure per 
physician discretion (in either a planned or bail-out fashion).  The physician may choose to perform 
the procedure in two or more stages due to the following conditions/scenarios including but not 
limited to: hypogastric patency, LSA patency, visceral vessel patency, decreased MEP/SEP 
potentials, at risk dominant segmental arteries, pulmonary status, or any patient whose physiologic 
limitations places them at risk  because of the expected length of surgery. The preferred method for 
planned staging is to create a controlled endoleak which provides limited and temporary perfusion 
to the aneurysm sac.  These methods include but are not limited to placing a bare metal stent in the 
celiac artery bridge, placing a bare metal stent in the bridge to an alternate visceral artery (ie:SMA 
or renal), or not completing distal seal in the aorta or iliac arteries.      
a. Planned Staged Procedure: Visceral artery bridge endoleak 
i. This refers to leaving open a portion of the covered stent bridge between the visceral 
manifold and target vessel. This is achieved by combining bare metal stents with 
covered stents to leave ~1-2cm of uncovered conduit along the pathway. This 
intentional endoleak is resolved in a subsequent intervention where the open portion 
is covered over by an additional covered stent. It is preferable to achieve this 
configuration with the bridge to the celiac artery but it can be done in analogous 
fashion with either the SMA or renal arteries.  
ii. Device Visualization and Preparation 
Refer to the Instructions for use provided for the bare metal stent for visualization 
and preparation instruction.  
iii. Bridging Stent Deployment 
Follow directions in the IFU when deploying bridging stents. Always deploy a 
covered stent in the leg of the visceral manifold per the Valiant Thoracoabdominal 
Stent Graft System IFU (9mm iCast at 8atm inflation pressure). When possible, 
covered stents should be used in the target vessel. The chain of covered stents should 
be non-continuous in nature with at least one bare metal balloon expandable stent 
connecting them. The segment of completely bare stent should be short (~1-2cm) 
with 2-3cm overlapping with covered stent on either side. Creation of the uncovered 
segment in as straight a configuration as the anatomy allows will facilitate wire 
passage during the completion procedure below.   
Note: The controlled endoleak should never be created by leaving a visceral 
manifold limb unconnected to a visceral vessel or with an uncovered segment >2cm 
due to the pressurization of the aneurysm sac.  If a visceral vessel is occluded, the 
corresponding visceral manifold limb should be plugged with a vascular plug and an 
alternative (patent) vessel utilized for the staging procedure.  The placement of the 
non-continuous chain of covered bringing stents and a bare metal stent helps direct 
flow while creating a controlled endoleak.   
iv. Completion  
Completion of the staged procedure is targeted for 4-6 weeks following the index 
procedure, but will be based on physician discretion, clinical presentation, and 
patient compliance.   
Note: The physician may choose to complete the procedure earlier if the patient is 
symptomatic or has other concerns for aneurysm sac growth or rupture.   

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Completion procedure may be performed under local or general anesthesia.  
Vascular access will be established in the brachial or axillary artery. The staged limb 
of the visceral manifold will be cannulated and the bare segment will be covered 
over by at least one iCast.  
b. Planned Stage Procedure: Delayed distal seal 
i. This refers to completing the visceral debranching (manifold to target arteries) with 
covered stents and subsequently leaving out one or more of the distal aortic/iliac 
components.  
ii. Device Visualization and Preparation 
Refer to the Instructions for use provided for the distal aortic/iliac components to be 
used.   
iii. Distal Aortic/Iliac Component Deployment 
Follow the study protocol or IFU for deploying the distal aortic/iliac components.   
iv. Completion  
Completion of the staged procedure is targeted for 4-6 weeks following the index 
procedure, but will be based on physician discretion, clinical presentation, and 
patient compliance.   
Note: The physician may choose to complete the procedure earlier if the patient is 
symptomatic or has other concerns for aneurysm sac growth or rupture.   
Completion procedure may be performed under local or general anesthesia.   
c. Bail-out Stage Procedure 
i. A bail-out method may be used for staging in the event patient status declines during 
the case or inability to technically complete the case.   
ii. Device Visualization and Preparation 
Refer to the Instructions for use provided for the components to be used.   
iii. Device Deployment 
Refer to the Valiant Thoracoabdominal Stent Graft System (IFU) for device 
deployment and implantation of the remaining components.   
iv. Completion due to patient status decline 
Completion of a bail-out staged procedure due to patient status should be completed 
as soon as clinically feasible following the index procedure, but will be based on 
physician discretion, clinical presentation, and patient compliance.   
Note: The physician may choose to delay staging if the patient has complications or 
there are concerns with completing the secondary procedure.   
v. Completion due to inability to technically complete the case 
Completion of a bail-out procedure due to technical challenges have the following 
options that present no more risk than the alternative of no treatment.   
a. Complete case at another date 
b. Medical management 
c. Convert to open surgical repair 
d. Referral to another facility/investigator that can complete the 
procedure 
 
Note:  If treating a dissected aorta, naturally occurring fenestrations will be utilized first, and if 
necessary, there may be the additional use of an excimer laser or perforating needle and catheter to 
perforate the intimal membrane.  This perforation will be used to enter either the false or true 
lumen in order to accommodate placement of the device. 

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Note:  Caution should be taken when relining previously placed graft material to prevent 
complications from graft on graft friction including decreased graft maneuverability and challenges 
repositioning. 
Note: For type 1 and 5 aneurysms the distal end of visceral bypass (VB) should be sized to provide 
the distal seal with the aorta and then proceed to Completion Procedures, listed below.  For type 2 
and 3, proceed to deployment of the infrarenal bifurcation and Endurant II limb stent graft 
instructions in the Medtronic Valiant Thoracoabdominal Stent Graft System IFU.   
Note: For proximal extension of the thoracic bifurcation, two Valiant thoracic grafts, either Valiant 
Captivia or Valiant Navion,  can be used.  One to extend the landing zone more proximally and one 
to layer to prevent wear. Deploy the Valiant  Captiva or Navion thoracic grafts according to their 
respective manufacturer’s IFU and continue according to the Medtronic Valiant Thoracoabdominal 
Stent Graft System IFU. 
Note: If the VB is too short or too small to provide distal seal, a Valiant Captivia Free-Flo stent 
graft or Endurant Limb may be used in place or in conjunction with the Visceral Bypass to provide 
adequate distal seal. For type 2 and 3 proceed to deployment of the infrarenal bifurcation and 
Endurant II limb stent graft instructions in the Medtronic Valiant Thoracoabdominal Stent Graft 
System IFU. If a commercially available Endurant limb or Valiant stent graft is used as the Visceral 
Bypass a commercially available Endurant mainbody stent graft with suprarenal fixation and a 
Gore cuff is required for adequate fixation.  See below for deployment procedures. 
Note: If treating a subject with an occluded visceral vessel, a vascular plug may be used to occlude 
the extra limb of the TAAA Visceral Manifold stent graft. 
 
C. Surgical Decision Pathway and Bailouts 
 

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Figure 4: Surgical decision path and possible bailouts  
 
D. Visceral Bypass (VB) Instructions (Endurant Long Limb) 
1. Insert a guidewire from the groin through the 16-mm limb of the thoracic bifurcation. 
2. Refer to the manufacturer’s IFU (Endurant) for visualization and preparation instructions.   
3. The proximal radiopaque marker of the VB stent graft should be aligned with the bifurcation of 
the thoracic bifurcation.   
4. Verify there is a 5 cm overlap with the 16 mm leg of the thoracic bifurcation.  
5. Deploy the VB according to the manufacturer’s IFU (Endurant).   
6. Leave the guidewire in place and remove the delivery system according the to manufacturer’s 
IFU (Endurant).   
 
E. Infrarenal Bifurcation (IB) Instructions (Endurant Mainbody)  
1. Refer to the manufacturer’s IFU (Endurant) for visualization and preparation instructions.   
2. Identify the guidewire that passes through the VB stent graft.  
3. From the ipsilateral groin access point, insert the delivery system over the guidewire.   
4. Slowly advance the bifurcated graft into the VB stent graft. 
5. Verify there is a 4-5cm overlap with the VB stent graft.  
6. Confirm the distal portion of the contralateral leg is above the aortic bifurcation.   
7. Confirm the radiopaque ring marker on the distal end of the contralateral leg is in a position to 
allow for cannulation from the contralateral iliac artery.   
8. Confirm the distal target landing zone relative to anatomical landmarks (i.e. internal iliac artery).   
9. Deploy the bifurcated graft according to the manufacturer’s IFU (Endurant).   
10. Release the tip capture mechanism according to the manufacturer’s IFU (Endurant).   
11. Remove the delivery system according the to manufacturer’s IFU (Endurant).   
12. Complete distal seal of the bifurcated graft into the common iliacs according the manufacturer’s 
IFU (Endurant).   
13. If the Endurant mainbody with suprarenal fixation is used deploy a Gore Aortic Extender 
Endoprosthesis according to the manufacturer’s IFU (Gore Excluder) over the suprarenal 
fixation stent of the bifurcated graft (Endurant mainbody) to seal and prevent endoleaks in the 
event the suprarenal fixation stent were to puncture the graft material.   
 
E. Use of spinal drain.  
o The use of a spinal drain is required for all non-staged procedures on subjects being 
treated for a Crawford Type I, II, III or V thoracoabdominal aneurysm 
o In the case of prior spinal surgery or any reason that would put the patient at 
higher risk for complications, the use is at the physician’s discretion 
o The use of a spinal drain on staged procedures is at the physician’s discretion 
 
 
Completion Procedures 
1.  At the physician’s discretion, line the bridging stent grafts with self-expanding bare metal 
stent(s) to provide additional radial support.  Note: In the event a bridging stent or self-
expanding stent needs reinforcement a Viabahn stent graft of appropriate sizing may be used.   
2. Begin to optimize spinal perfusion.   
3. After deployment of all stent grafts, all contact points will be balloon angioplastied.   
4. Perform an angiogram to verify stent graft apposition, seals, patency, device defects and any 
endoleaks.  Perform additional procedures, such as ballooning, cuff placement, or use of 
covered stent grafts as necessary to treat endoleaks or device failures.   

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5. Remove all sheaths, wires, and remaining accessories and repair of arterial access sites using 
standard surgical closure techniques. 
6. Dopperable signals will be confirmed in bilateral lower extremities and the access upper 
extremities.  
7. Once adequate perfusion is confirmed, heparinization will be reversed. 
8.  In the event of patient death an autopsy may be performed.     
 
Post-operative Care 
Patients may remain intubated and be transferred to the ICU standard post-operative care.  Patients 
with a spinal drain will remain in bed with optimization of spinal perfusion pressure for 48-72 hours 
whenever possible.  Post-operative care will be tailored to the patient taking into account events of surgery 
as well as pre-operative comorbidities to optimize the patient’s recovery.  On post-operative day two, 
attempts will be made to normalize the MAP and clamp the spinal drain if used.  Prior to spinal drain 
removal all coagulopathies and low platelet counts are corrected.  The patient’s neurological status is 
closely watched for the next 4-6 hours.  If it remains stable, the drain is removed and the patient is 
monitored for hypoxia, anemia, and hypotension. In the event of patient death an autopsy may be 
performed.  Prior to discharge from the hospital, the following tests will be performed:  
o 
Physical examination 
o 
Complete blood count to evaluate white blood cells, hemoglobin, and platelets 
o 
Basic metabolic panel to evaluate creatinine 
o 
Prothrombin time (at physician’s discretion) 
o 
Partial thromboplastin time (at physician’s discretion) 
o 
CTA or CT with contrast of the chest, abdomen and pelvis if renal function allows.  If 
renal function does not allow CT with contrast, an alternative contrast-enhanced imaging 
modality or, at a minimum, CT non-contrast in conjunction with Duplex ultrasound will be 
used at physician discretion 
 
Follow-up Visits 
 
All patients will undergo follow-up at one month, six months, twelve months and then annually for 
five years (as depicted below in Table 5: Follow-Up).  At each of the follow-up visits the following tests 
will be performed:  
o 
Physical examination 
o 
SF36 survey testing 
o 
Complete blood count to evaluate white blood cells, hemoglobin, and platelets 
o 
Basic metabolic panel to evaluate creatinine 
o 
CTA or CT with contrast of the chest, abdomen and pelvis if renal function allows.  If 
renal function does not allow CT with contrast, an alternative contrast-enhanced imaging 
modality or, at a minimum, CT non-contrast in conjunction with Duplex ultrasound will be 
used at physician discretion  
o 
Pregnancy test (for female patients of child bearing age) 
o 
Device x-ray may be used if potential device integrity issues are identified but unable to be 
confirmed by CT. This will be done per local standard of care with A/P, Lateral and 
Bilateral Oblique Images obtained. 
b.  
Study duration and number of study visits required of research participants. 
 
Patients included in the study will undergo follow-up at one month, six months, twelve months 
and then annually for five years.  In the event of patient death, an autopsy may be performed.   
 

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Table 5. Follow-up Table  
 
 
Month 
 
Pre-
op 
Intra-op 
Index 
Pre- 
discharge 
Intra-op 
Completion 
(if staged) 
Pre- 
discharge  
(if staged) 
1 
6 
12 
24 
36 
48 
60 
CTA/CT with 
contrast of Chest, 
Abdomen, and 
Pelvis 
X2,3 
 
X2, 8 
 
X2, 8 
X2 
X2 
X2 
X2 
X2 
X2 
X2 
Angiography 
X3 
X 
 
 
 
 
 
 
 
 
 
 
Blood Tests 
X4 
X5, 6 
X4, 8 
X4 
X4, 8 
X4 
X4 
X4 
X4 
X4 
X4 
X4 
Clinical Exam 
(including ABI) 
 
X7 
 
 
X8 
 
 
 
X8 
 
X7 
 
X7 
 
X7 
 
X7 
 
X7 
 
X7 
 
X7 
Branch Patency 
(duplex ultrasound) 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
1  Device X-ray may be requested to provide more focused imaging if potential device integrity issues are identified, but are unable to be 
confirmed, using CT. 
2   If renal function does not allow for CTA or CT with contrast, an alternative contrast-enhanced imaging modality or, at a minimum, non-
contrast CT in conjunction with duplex ultrasound may be used at physicians discretion.   
3   Pre-procedure angiography may be requested at discretion of film reviewer. 
4   Blood tests include CBC for hemoglobin and BMP for creatinine. 
5   Blood test for ACT. 
6   Other intra-op labs for anesthesia.   
7   Urine pregnancy test (for female patients of childbearing age). 
8   CT, Duplex, ABI and labs are optional at the pre-discharge and one month visits between staging procedures. 
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. 
 
N/A 
 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped. 
 
N/A 
 
e. Justification for inclusion of a placebo or non-treatment group. 
 
N/A 
 
f. Definition of treatment failure or participant removal criteria. 
 
N/A 
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. 
 
N/A 
5. 
 
5. Inclusion/Exclusion Criteria 
 

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Modified Inclusion Criteria  
A patient may be entered into the study if the patient has at least one of the following: 
• An aneurysm with a maximum diameter of >  5.5 cm or 2 times the normal diameter just 
proximal to the aneurysm using orthogonal (i.e., perpendicular to the centerline) 
measurements 
• Aneurysm with a history of growth >  0.5 cm in 6 months  
• Saccular aneurysm deemed at significant risk for rupture 
• Symptomatic aneurysm greater than or equal to 4.5 cm 
• Axillary or brachial and iliac or femoral access vessel morphology that is compatible with 
vascular access techniques, devices or accessories, with or without use of a surgical conduit 
• Proximal landing zone for the thoracic bifurcation stent graft that has: 
o ≥ 2.5 cm of healthy/nondiseased tissue (including previously placed graft material) 
(neck) distal to the left subclavian artery (LSA) and a diameter in the range of 26-42 
mm 
o Adequate distance from the celiac artery, in order to accommodate cannulation from 
the antegrade access point when considering the total deployed length of the thoracic 
bifurcation and visceral manifold 
• Minimum branch vessel diameter greater than 5 mm  
• Iliac artery distal fixation site, including both native tissue and previously placed graft, 
greater than or equal to 15 mm in length and diameter in the range of 8 – 25 mm 
• Age: ≥ 18 years old 
• Life expectancy: > 1 year 
 
Exclusion Criteria 
General exclusion 
• Patient is a good candidate for and elects open surgical repair 
• Can be treated in accordance with the instructions for use with a legally marketed 
endovascular prosthesis 
• Is eligible for enrollment in a manufacturer-sponsored IDE at the investigational site 
• Unwilling to comply with the follow-up schedule 
• Inability or refusal to give informed consent by patient or legal representative 
• Patient is pregnant or breastfeeding 
• Patient has a contained rupture 
• Patient has a ruptured aneurysm 
• Patient has a dissection in the portion of the aorta intended to be treated 
• Obstructive stenting of any or all of the visceral vessels 
• 
Poor performance status including two major system failures (including but not limited to 
cardiovascular, pulmonary, renal, hepatobiliary, and neuromuscular) 
• Prior aneurysm repair that would involve relining of the previously placed graft material 
requiring placement of the investigational system in a landing zone that expands beyond any 
limits of the previously placed graft material 
Medical exclusion criteria 
• Known sensitivities or allergies to the materials of construction of the devices, including 
nitinol (Nickel: Titanium), polyester, platinum-iridium, polytetrafluoroethylene (PTFE), 
platinum, gold, polyethylene, or stainless steel.   
• Known hypersensitivity or contraindication to anticoagulation or contrast media that cannot 
be adequately medically managed  
• Uncorrectable coagulopathy 

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• Body habitus that would inhibit x-ray visualization of the aorta or exceeds the safe capacity 
of the equipment 
• Patient has had a major surgical or interventional procedure unrelated to the treatment of the 
aneurysm planned < 30 days of the endovascular repair 
• Unstable angina (defined as angina with a progressive increase in symptoms, new onset at 
rest or nocturnal angina) 
• Systemic or local infection that may increase the risk of endovascular graft infection 
• Baseline creatinine greater than or equal to 2.0 mg/dL  
• History of connective tissue disorders (e.g., Marfan Syndrome, Ehler’s Danlos Syndrome) 
Anatomical exclusion criteria 
• Thrombus or excessive calcification within the neck of the aneurysm 
• Anatomy that would not allow maintenance of at least one patent hypogastric artery 
• Anatomy that would not allow primary or assisted patency of the left subclavian artery 
 
Expanded Selection criteria 
Subjects who fail to meet inclusion criteria for the primary study arm may be enrolled under an expanded 
selection arm.  The study team will report at intervals of every five patients treated under the IDE 
regardless of study arm.  The interim report will be submitted to the FDA within ten days following the 30-
day follow-up of the fifth patient enrolled. 
Inclusion Criteria 
• Patients that meet the criteria for inclusion in the primary study arm but have one or 
more of the following criteria which would exclude them from the primary study arm: 
o Minimum branch vessel diameter less than 5 mm 
o Urgent or emergent presentation 
o Patient has a contained rupture 
o Patient has a ruptured aneurysm  
o Patient has a type B dissection (subacute or chronic) in the portion of the aorta 
intended to be treated 
o Poor performance status including two major system failures (cardiovascular, 
pulmonary, renal, hepatobiliary, and neuromuscular) 
o Baseline creatinine greater than or equal to 2.0 mg/dL 
o Anatomy that would not allow for maintenance of at least one hypogastric artery 
o Anatomy that would not allow for primary or assisted patency of the left 
subclavian artery 
o Prior aneurysm repair that would involve relining of the previously placed graft 
material requiring placement of the investigational system in a landing zone that 
expands beyond any limits of the previously placed graft material 
o Obstructive stenting involving any or all visceral vessels 
Or 
• Patients that meet the criteria for inclusion in the primary study arm and:  
o Would not be eligible for the primary study arm per a documented reason other 
than those outlined above, and 

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o Per the opinion of the Principal Investigator, with concurrence of the IRB, 
alternative therapies are unsatisfactory and the probable risk of using the 
investigational device is no greater than the probable risk from the disease or 
condition. 
 
 
6. Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used. 
b. Justification and safety information if FDA approved drugs will be administered for non-FDA 
approved indications or if doses or routes of administration or participant populations are 
changed. 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.  
 
Potential Study Device Benefits and Risks Based on Leveraged Clinical Information 
Patients diagnosed with TAAA have a poor natural history and require surgical intervention to 
extend life.  Several repair techniques have been developed, but each carry risk.  As discussed 
previously, open repairs are durable but have substantial perioperative mortality and 
postoperative morbidity.  Endovascular techniques are plagued by high procedural complexity 
and poor branch vessel patency, leading to accrual of costs over time.  Parallel techniques may 
have poor seal and may be prone to endoleak.  In contrast, the manifold approach has 
circumferential seal at the proximal end of the system.  It has relatively simple case planning 
and it has virtually no ischemic time.  Due to these advantages, we believe the novel proposed 
technique may overcome some of the current clinical risks with other approaches and may be 
associated with reduced costs and better quality of life for the recipient.   
Patients who participate in this study may benefit from having a less invasive procedure 
compared to open repair of their thoracoabdominal aortic aneurysm.  We expect the amount of 
discomfort, total blood loss, recovery time, and overall hospital stay to be less than open repair.  
Many of the patients presenting with a thoracoabdominal aneurysm are not candidates for open 
repair due to existing comorbidities.  With the progressive nature of the disease, these patients 
have limited options for medical intervention and are willing to assume a higher amount of risk.  
Patients who have a planned staged procedure may benefit from reduced SCI events, contrast 
exposure, fluids, procedure time, and less overall insult to their pulmonary status. We expect the 
amount of discomfort, total blood loss, recovery time, and overall hospital stay to be similar to 
an unstaged repair.  These subjects would be placed at increased risks related to a second 
procedure including those identified in the risk analysis.  With the progressive nature of the 
disease, these patients have limited options for medical intervention and may be willing to 
assume a higher amount of risk.    
Patients after treatment with the Valiant Thoracoabdominal Stent Graft System may also have a 
better quality of life measure on objective QOL instruments.  Using the Medical Outcomes 
Study Short Form 36 Item Survey (SF-36), we will study the physical functioning of the 
patients, role limitations as a result of physical problems, bodily pain, general health perception, 
vitality (frequency of feeling full or tired), social functioning, and general mental health. Prior 
investigations have not been performed to identify these critical patient focused outcomes after 
endovascular repair of TAAA.   

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Institution Experience and Infrastructure 
Johns Hopkins patients receive the most advanced care and treatment that today’s 
medical research offers through over 350 clinical trials. As part of Johns Hopkins’s legacy in 
clinical research, Johns Hopkins physician scientists lead nationally sponsored cooperative 
group study programs. Additionally, a growing variety of industry-sponsored and physician-
investigator drug and device trials are conducted through the Johns Hopkins Center for Research 
Excellence in Surgical Trials (CREST).  Johns Hopkins Hospital is the primary teaching 
hospital of Johns Hopkins School of Medicine, University of Baltimore, Maryland..  Johns 
Hopkins also has an advanced electronic medical record and clinical information system for data 
management and access.  Johns Hopkins Research makes use of an internet-based database 
platform and clinical research management suite for managing clinical research and specialized 
medical records.  The Vascular Surgery Department at Johns Hopkins has several dedicated 
resources from CREST.  There is a full time sr. clinical research program manager, two full time 
research coordinators, and a full time sr. research nurse.  There is also a biostatistician available 
and research monitors can be made available on an as-needed basis.  Johns Hopkins CREST has 
performed industry-sponsored IDE trials along with several industry-sponsored post approval 
studies.  Johns Hopkins Hospital is affiliated with six Institutional Review Boards to review 
human subject protections and has a dedicated conflict of interest committee which reviews and 
identifies Johns Hopkins Investigator conflicts of interest and develops appropriate conflict of 
interest management plans.  
 
 
7. Study Statistics 
A. Primary outcome variable. 
 
The primary technical safety endpoint is freedom from major adverse events (MAE) at 30 days or 
during hospitalization if this exceeds 30 days. Major adverse events include all-cause mortality 
within 30 days of the procedure, bowel ischemia, myocardial infarction, paraplegia, renal failure, 
respiratory failure, and stroke. 
 
The primary effectiveness endpoint is the proportion of study subjects with treatment success at 1 
year. Treatment success is defined as a composite of technical success and freedom from the 
following:  
o Aneurysm enlargement i.e., >5mm as compared to any previous CT measure using 
orthogonal (i.e., perpendicular to the centerline) measurements 
o Aneurysm rupture 
o Aneurysm-related mortality 
o Conversion to open repair  
o Secondary intervention for migration, Type I and III endoleaks, device integrity failure 
(e.g., fracture), and patency-related events (i.e., device component stenosis or occlusion 
and embolic events) 
 
The primary non-technical endpoint is improvement in quality-of-life scores (by SF36) and reduced 
1 year costs for patients who undergo endovascular repair vs open surgery. 
 
B. Secondary outcome variables. 
 
Secondary endpoints include: 
• Technical success and the individual components of technical success:  

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o Successful delivery 
o Deployment at the intended implantation site 
o Patency of all endovascular graft and stent components 
o Absence of device deformations requiring unplanned placement of an additional device  
o Absence of inadvertent covering of aortic branch vessels 
o Successful withdrawal  
• Freedom from the individual components of the primary safety endpoint at 30 days.   
o 
Death 
o 
Bowel ischemia 
o 
Myocardial infarction 
o 
Paraplegia 
o 
Renal failure 
o 
Respiratory failure 
o 
Stroke 
• Freedom from paraparesis at 30 days 
• Treatment success and freedom from the following at each follow-up interval: 
o Aneurysm enlargement 
o Aneurysm-related mortality  
o Aneurysm rupture 
o Conversion to open repair 
o Secondary intervention for: 
o Migration 
o Type I endoleak 
o Type III endoleak  
o Device integrity failure (e.g., fracture)  
o Patency-related events (i.e., device stenosis or occlusion and embolic events)  
o Renal failure 
o All-cause mortality 
o Endoleaks 
o Device integrity failure (e.g., fracture) 
o Patency –related events (i.e., endovascular graft or stent component stenosis or 
occlusion and embolic events) 
o Other device-related events 
 
C. Statistical plan including sample size justification and interim data analysis. 
 
Sample Size Justification 
The sample size for the study is limited to 16 patients (10 subjects in the primary study arm and 6 
subjects in the expanded selection criteria arm), as this is adequate to provide preliminary clinical safety 
data and effectiveness of the device and provide the comparator group for open thoracoabdominal surgery 
patients.  The device, while novel, has been evaluated in a clinical setting and has initially demonstrated 
both safety and effectiveness.  The limited sample size allows adequate patient data to be collected under a 
controlled protocol without exposing a large patient population to the risk associated with a novel device 
design. The safety and effectiveness data collected in this study will be pooled with other physician 
sponsored investigational device exemptions (PS-IDEs) evaluating the Visceral Manifold System and 
should be sufficient to develop an appropriate pivotal study. 

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In reference to the objective of cost of TAAA delivery, prior studies suggest the one-year costs 
associated with open TAA repairs are approximately $150,000+/-$10,000. 56Assuming a power of 80% and 
alpha=0.05, we would need 20 patients per group to detect a difference of $20,000 between the mean one-
year costs of open TAA repair vs TEVAR.  Longitudinal costs over a one year period, inclusive of global 
healthcare costs (readmission, outpatient care, rehabilitation stays) are not available from the literature, but 
would be analyzed in this study, and thus inform healthcare policy, reimbursement strategies, and hospital 
administrators. 
Data Presentation and Analysis Plan 
 The primary purpose of this study is to evaluate the safety of this device as there are no or very 
limited devices and clinical options available for this patient population.  The primary safety endpoint of 
this study is freedom from major adverse events (MAE) at 30 days or during hospitalization if this exceeds 
30 days.  Major adverse events include death, bowel ischemia, myocardial infarction, paraplegia, renal 
failure, respiratory failure, and stroke.  The primary safety endpoint will be analyzed to determine statistical 
significance when compared to a target performance goal.  A literature review of outcomes of open surgical 
repair was used to create the performance goal as there is not a comparable endovascular option to use for 
analysis.  The performance goal was selected based on the range of subjects experiencing a major adverse 
event at 30 days.  The range was calculated based on assumptions of the minimum and maximum number 
of subjects experiencing at least one MAE in the historical open surgical repair group (Table 6).  Based on 
the literature reviewed and the above assumptions the range of subjects experiencing at least one MAE in 
the open surgical repair group is 30.5% to 77.4%.   
The primary effectiveness endpoint is the proportion of the study subjects with treatment success at 
1 year.  Similarly, the data will be presented as quality outcomes with the number of study subjects with 
treatment success compared to the overall patient population.   
 
The primary non-technical endpoint is patient quality of life domains at one year by SF36 testing at 
one year, and other follow-up intervals.   
 
Additionally, data outcomes from this study will be entered into a common vascular database so 
that data can be pooled with other PS-IDEs.  This would provide consistent reporting across the PS-IDEs.  
Additionally, the PS-IDEs will be evaluating the same device and endpoints to allow for a pool-ability of 
data across the sites.  The data will be separated into two separate study arms: primary study arm and 
expanded selection arm. The primary cost related outcomes are total, global healthcare costs from time of 
surgery to one year after treatment with the Valiant Thoracoabdominal Stent Graft System. 
Statistical Methods 
The primary hypothesis of the Visceral Manifold Study is the number of subjects experiencing a 
major adverse event through 30 days will be less than a target performance goal (PG) of 50%. The PG was 
determined by using a conservative target that is approximately the average of the open surgical repair 
MAE rate calculated above (30.5%-77.4%, Table 6).  The anticipated test device 30 day MAE rate was 
based on the current rate of MAE’s (26%, Table 7) observed in 20 subjects meeting inclusion criteria into 
the primary study as of June 2016.   
The sample size for the Visceral Manifold Study was determined using an exact method based on a 
one-sided 2.5% significance level and an anticipated 26% investigational device 30 day major adverse 
event rate.  Based on these assumptions, a sample size from the pooled PS-IDE data of 46 subjects provides 
at least 80% power to test the primary hypothesis.   

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Table 6. Historical Comparison for Primary Safety Endpoint (MAE Rate at 30 days for Open 
Repair) 
Reference 
# of 
Patients 
Mortality 
Bowel 
Ischemia 
Myocardial 
Infarction 
Paraplegia 
Renal Failure 
Respiratory 
Failure 
Stroke 
Rigberg et 
al 
1010 
191 (19%) 
 
 
 
 
 
 
Becquemin 
et al 
1678 
90 (5.4%) 
51 (3%) 
20 (1.2%) 
16 (1%) 
289 (17.2%) 
124 (7.4%) 
12 (0.7%) 
Murana et 
al 
542 
46 (8.5%) 
 
 
22 (4.2%) 
 
 
 
Ferrer et al 
257 
16 (6.2%) 
 
 
53 (20.8%) 
31 (12.3%) 
31 (12.3%) 
 
Bensley et 
al 
450 
45 (10%) 
 
10 (2.4%) 
 
48 (10.7%) 
202 
(45.1%) 
9 (2.2%) 
Nathan et al 
83 
6 (5.6%) 
 
 
 
 
 
 
Dayama et 
al 
682 
68 (10%) 
 
87 (12.9%) 
 
117 (17.2%) 
286 (42%) 
 
Ferrante et 
al 
200 
5 (2.5%) 
 
25 (12.8%) 
 
22 (11%) 
27 (13.8%) 
 
Tsilimparis 
et al 
1091 
58 (5.4%) 
 
87 (8%) 
 
109 (10%) 
229 (21%) 
 
Piazza et al 
7833 
1331 
(17%) 
 
 
587 (7.5%) 
1488 (19%) 
2819 (36%) 
 
Total 
13826 
1855/1382
6  
51/1678  
229/4101  
678/10310  
2104/12191  
3718/12191  21/2128  
Rate of 
MAE at 30 
Days for 
Open 
Surgical 
Repair 
 
13.4% 
3.0% 
5.6% 
6.6% 
17.3% 
30.5% 
1.0% 
Table 7. Historical Comparison for Expected Investigational Device 30 Day MAE Rate (Outcomes 
of subjects treated with the Visceral Manifold System and meeting inclusion into the 
primary study as of June 2016) 
Dataset 
Mortality 
Bowel 
Ischemia 
Myocardial 
Infarction 
Paraplegia 
Renal Failure 
Respiratory 
Failure 
Stroke 
Subjects meeting 
VMS  
PS-IDE I/E 
criteria 
0/20 (0%) 
0/20 (0%) 
0/20 (0%) 
2/20 (9.5%) 
1/20 (5%) 
3/20 (14%) 
0/20 (0%) 
 
Limitations of the Study 
Limitations of the study are that it is a single center study with a small patient population.   
Risk Analysis  
The risk analysis includes a description and analysis of all increased risks to the research subjects 
and how these risks will be minimized. The risks can be separated into three categories: procedural-related 
risks, device performance-related risks, and device material-related risks.    
 

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D. Early stopping rules. 
 
The Sanford DSMB will be responsible for examining accumulated safety and other relevant data at 
prespecified points during the course of the study in order to make recommendations concerning 
continuation, termination, or modification of the study. Based on the results of its deliberations, the DSMB 
can recommend continuation of the study unchanged, study interruption, study termination, modification of 
the study, or alteration in the data monitoring plan.  
 
8. Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency. 
b. Steps taken to minimize the risks. 
c. Plan for reporting unanticipated problems or study deviations. 
d. Legal risks such as the risks that would be associated with breach of confidentiality. 
e. Financial risks to the participants. 
 
The risk analysis includes a description and analysis of all increased risks to the research subjects 
and how these risks will be minimized. The risks can be separated into three categories: procedural-related 
risks, device performance-related risks, and device material-related risks.    
 
Procedural-related risks  
Procedural related risks including general and device specific procedural risks can result in several 
serious harms to the patient.  These risks can be mitigated in a number of ways including strict adherence to 
the investigational protocol, patient eligibility criteria, procedures performed by trained and qualified 
physicians, use of standard surgical and endovascular techniques, and regular follow-ups.  Although the risk 
is lowered by following these mitigation strategies the risk cannot be completely eliminated.  However, the 
potential benefit of the Valiant Thoracoabdominal Stent Graft System as compared to other surgical 
techniques outweighs the potential procedural related risks to the patient.    
 
General procedure related risks:  
Contrast toxicity can result in renal insufficiency or renal failure. Increased procedural difficulty 
may lead to an increase in the volume of contrast required. Adhering to the patient selection criteria should 
mitigate the risk of contrast induced nephropathy, but it can still occur.  
Allergic response to anticoagulation can occur. Patients who undergo the proposed procedure will 
require anticoagulation. A complete history of the patient before the procedure and adhering to the 
anticoagulant’s product standards will mitigate the risk of hypersensitivity reaction.  
Central nervous damage and subsequent paraplegia can occur when a significant amount of the 
aorta has stent graft coverage and a patient then becomes hemodynamically unstable. Conformance to 
patient selection criteria and proper spinal cord protection measures will mitigate the risk of spinal cord 
ischemia and subsequent paraplegia, but they can still occur.  
Peripheral nerve damage can occur at the surgical access sites. This procedure has 3 surgical access 
sites. Utilizing accepted surgical techniques performed by trained physicians will mitigate the risk of 
peripheral nerve damage, but some nerve damage can still occur.  
Paraplegia can occur when a stent graft is deployed in the aorta and blocks the lumbar arteries 
resulting in spinal cord ischemia.  Although the risk can be mitigated by employing proper spinal protection 
measures (i.e. spinal drain), by screening patients for major lumbars feeding the spinal cord where the graft 
is intended to go, and for screening patients for occluded internal iliac arteries, paraplegia can still happen.    
Injury to access vessel from sheath placement can occur as a result of improper sheath sizing or 
placement. Adherence to good surgical technique minimizes the risk of damaging sites of sheath 
placement.  

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Dissection of a vessel can result from excessive wire manipulations due to an inability to access 
target vessels. Using proper endovascular technique and coming from a left arm access (provides a more 
direct path to the aorta) can mitigate this risk, but dissection can still occur.  
Embolism due to excessive wire manipulations may result in embolization in the arch or in the 
descending thoracic aorta resulting in occlusion of a great vessel, visceral branch vessel, or an extremity. 
Using proper endovascular and surgical techniques as well as accessing through the left arm to provide a 
straighter path to the aorta lessen the risk, but emboli may still occur.  
Branch artery or parenchyma damage of ischemia can occur from blockage or occlusion of a branch 
vessel.  Using fluoroscopic guided placement of devices, careful case planning, careful measuring when 
modifying devices, verification of alignment when resheathing devices, partial deployment to ensure proper 
placement, use of appropriate sized branch vessel stents and complaint transition zone between stents and 
native vessels, and monitoring devices over time will help mitigate this risk, but damage from ischemia can 
still occur.   
Systemic effects including increased risks of morbidity and mortality may be associated with this 
surgery.   Using proper endovascular technique, strict adherence to the investigation protocol, and 
monitoring of device over time can mitigate this risk, but system effects can still occur.   
Local effects at the access site including wound infection, hematomas, and seromas, arterial or 
venous damage may occur.  The risk can be mitigated by using accepted surgical technique by a trained 
physician, but local effects may still occur.   
 
Device-specific procedure related risks: 
Failure to access the aorta can result in vessel damage from wire manipulations and procedural 
failure.  Using proper endovascular technique, coming from a left arm access (provides a more direct path 
to the aorta), proper patient selection, and careful case planning for sizing can mitigate this risk, but vessel 
damage and procedural failure may still occur.   
Inaccurate deployment of the thoracic bifurcation due to mal-rotation or inaccurate placement may 
lead to vessel occlusion and end organ or limb ischemia.  Although the risk of inaccurate deployment can 
be mitigated by careful case planning, use of partial deployment and pre-cannulated wires to aid 
positioning, and use of radiopaque alignment markers, mal-rotation or inaccurate placement may still 
occur.   
Inaccurate deployment of the visceral manifold due to mal-rotation or inaccurate placement may 
lead to vessel occlusion and end organ or limb ischemia.  Although the risk of inaccurate deployment can 
be mitigated by careful case planning, use of partial deployment and pre-cannulated wires to aid 
positioning, and use of radiopaque alignment markers, mal-rotation or inaccurate placement may still 
occur.   
Inaccurate deployment of visceral bypass due to mal-rotation or inaccurate placement may lead to 
vessel occlusion and end organ or limb ischemia.  Although the risk of inaccurate deployment can be 
mitigated by careful case planning, pre-cannulated wires to aid positioning, and use of radiopaque 
alignment markers, mal-rotation or inaccurate placement may still occur.   
Inaccurate deployment of infrarenal bifurcation due to mal-rotation or inaccurate placement may 
lead to vessel occlusion and end organ or limb ischemia.  Although the risk of inaccurate deployment can 
be mitigated by careful case planning, pre-cannulated wires to aid positioning, and use of radiopaque 
alignment markers, mal-rotation or inaccurate placement may still occur.   
Inaccurate deployment of iliac limbs due to mal-rotation or inaccurate placement may lead to vessel 
occlusion and end organ or limb ischemia.  Although the risk of inaccurate deployment can be mitigated by 
careful case planning, pre-cannulated wires to aid positioning, and use of radiopaque alignment markers, 
mal-rotation or inaccurate placement may still occur.   

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Failure to deploy the thoracic bifurcation may result in increased procedural time, conversion to 
open, or procedural failure.  The risk can be mitigated by having additional components available and 
having tools prepared to perform open surgical repair if necessary.   
Failure to deploy the visceral manifold may result in increased procedural time, conversion to open, 
or procedural failure.  The risk can be mitigated by having components available and having tools prepared 
to perform open surgical repair if necessary.   
Failure to deploy the visceral bypass may result in increased procedural time, conversion to open, or 
procedural failure.  The risk can be mitigated by having additional components available and having tools 
prepared to perform open surgical repair if necessary.   
Failure to deploy the infrarenal bifurcation may result in increased procedural time, conversion to 
open, or procedural failure.  The risk can be mitigated by having additional components available and 
having tools prepared to perform open surgical repair if necessary.   
Failure to deploy the iliac limbs may result in increased procedural time, conversion to open, or 
procedural failure.  The risk can be mitigated by having additional components available and having tools 
prepared to perform open surgical repair if necessary.  
Inaccurate deployment of the iCast covered, balloon expandable branch vessel stent due to mal-
rotation or inaccurate placement may lead to vessel occlusion and end organ or limb ischemia.  Although 
the risk of inaccurate deployment can be mitigated by careful case planning, pre-cannulated wires to aid 
positioning, and use of radiopaque alignment markers, mal-rotation or inaccurate placement may still 
occur.   
Failure to deploy the iCast covered, balloon expandable branch vessel stent may result in increased 
procedural time, conversion to open, or procedural failure.  The risk can be mitigated by having additional 
components available and having tools prepared to perform open surgical repair if necessary.   
Displacement of the thoracic bifurcation due to incomplete apposition of the stent graft, non-
compatible or damaged components/accessories, or size mismatch can result in endoleak, aneurysm 
enlargement, aneurysm rupture, vessel occlusion, end organ or limb ischemia.  Although the risk can be 
mitigated with the use of careful case planning, strict adherence to the investigation procedure, completion 
angiograms, regular follow-ups, and treatment with cuffs, ballooning, or additional stent grafts, the risk of 
displacement still exists.   
Displacement of the visceral manifold due to incomplete apposition of the stent graft, non-
compatible or damaged components/accessories, or size mismatch can result in endoleak, aneurysm 
enlargement, aneurysm rupture, vessel occlusion, end organ or limb ischemia.  Although the risk can be 
mitigated with the use of careful case planning, strict adherence to the investigation procedure, completion 
angiograms, regular follow-ups, and treatment with cuffs, ballooning, or additional stent grafts, the risk of 
displacement still exists.   
Displacement of the visceral bypass due to incomplete apposition of the stent graft, non-compatible 
or damaged components/accessories, or size mismatch can result in endoleak, aneurysm enlargement, 
aneurysm rupture, vessel occlusion, end organ or limb ischemia.  Although the risk can be mitigated with 
the use of careful case planning, strict adherence to the investigation procedure, completion angiograms, 
regular follow-ups, and treatment with cuffs, ballooning, or additional stent grafts, the risk of displacement 
still exists.  
Displacement of the infrarenal bifurcation due to incomplete apposition of the stent graft, non-
compatible or damaged components/accessories, or size mismatch can result in endoleak, aneurysm 
enlargement, aneurysm rupture, vessel occlusion, end organ or limb ischemia.  Although the risk can be 
mitigated with the use of careful case planning, strict adherence to the investigation procedure, completion 
angiograms, regular follow-ups, and treatment with cuffs, ballooning, or additional stent grafts, the risk of 
displacement still exists.   
Displacement of the iliac limbs due to incomplete apposition of the stent graft, non-compatible or 
damaged components/accessories, or size mismatch can result in endoleak, aneurysm enlargement, 

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aneurysm rupture, vessel occlusion, end organ or limb ischemia.  Although the risk can be mitigated with 
the use of careful case planning, strict adherence to the investigation procedure, completion angiograms, 
regular follow-ups, and treatment with cuffs, ballooning, or additional stent grafts, the risk of displacement 
still exists.   
Displacement of the iCast covered, balloon expandable branch vessel stent due to incomplete 
apposition of the stent graft, non-compatible or damaged components/accessories, or size mismatch can 
result in endoleak, aneurysm enlargement, aneurysm rupture, vessel occlusion, end organ or limb ischemia.  
Although the risk can be mitigated with the use of careful case planning, strict adherence to the 
investigation procedure, use of industry standard seal zone lengths and oversizing, completion angiograms, 
regular follow-ups, treatment with cuffs, ballooning, or additional stent grafts, the risk of displacement still 
exists.   
Inadvertent internal iliac occlusion and ischemic colitis due to vessel occlusion can occur.  The risk 
can be mitigated with the use of careful case planning, using proper endovascular technique, completion 
angiograms, and regular follow-ups.   
 
Device-related risks 
There are device-related risks of the modular components succumbing to material fatigue resulting 
in component separation, endoleak, kinking, or migration.  These risks can be mitigated several ways 
including adhering to industry standard seal zone lengths, proper oversizing, lining branch stents with self-
expanding stents, regular follow-ups to identify early evidence of migration or separation and allow for 
appropriate treatment, by the use of completion angiography coupled with cuffs, ballooning, or additional 
stent grafts if evidence of endoleak.    
Migration can occur when a stent graft is deployed with inadequate landing zone, improper 
oversizing, resulting in vessel occlusion, endoleak, aneurysm enlargement, or aneurysm rupture.  Although 
the risk of migration can be mitigated by using industry accepted overlaps, proper oversizing, accepted 
suture techniques, and adhering to the follow up schedule, it can still occur.   
Component separation can occur when a stent graft is deployed with improper overlap, improper 
oversizing, or when a suture line fails, resulting in vessel occlusion, endoleak, aneurysm enlargement, or 
aneurysm rupture.  Although the risk of component separation can be mitigated by using industry accepted 
overlaps, proper oversizing, accepted suture techniques, and adhering to the follow up schedule, it can still 
occur.   
Graft occlusion due to angulation, kink, or mal-alignment modular components can lead to implant 
thrombosis.  Using careful case planning for appropriate sizing, adherence to the investigational protocol, 
lining with self-expanding stents and regular patient follow-up can mitigate this risk, but graft occlusion 
can still occur.     
Endoleak and endotension due to inadequate seal between graft and components, graft permeability, 
poor graft seal, improper oversizing, suture line holes, or graft wear can result in aneurysm enlargement, 
aneurysm rupture, or retrograde flow from branch arteries.  Although the risk can be mitigated with 
completion angiograms, regular follow-ups, and treatment with secondary procedures or devices (cuffs, 
balloons, and stents), endoleak or endotension can still occur.   
Graft infection can result in fever, sepsis, and conversion to open repair.  The risk can be mitigated 
by following the investigational protocol, administering post-operative blood tests to monitor condition, use 
of antibiotics, and regular follow-up.  Even with these mitigation strategies the risk of graft infection still 
exists.   

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Branch stent graft kink or crush can result from aneurysm sac remodeling, stent graft migration, or 
fatigue of implant.  Although the risk can be mitigated by lining the bridging stents with self-expanding 
bare metal stents, kink can still occur.  And if it does it may result in vessel occlusion or embolism.   
Aortic stent graft kink may result in misalignment of kink of components ultimately resulting in 
vessel occlusion or embolism.  Although the risk can be mitigated by careful case planning,  proper subject 
selection, lining bridging stents with self-expanding stents, adherence to the investigational protocol, and 
regular subject follow-ups, it can still happen.   
Stent breakage due to manufacturer flaw, fatigue, poor placement of stent, or compatibility with 
other components can result in vessel occlusion, embolism, migration, separation, vascular trauma, and 
vessel rupture.  Although the risks can mitigated with the use of careful case planning for placement and 
sizing, proper oversizing, use of compatible components, and regular follow-up, stent breakage can still 
occur.      
Branch vessel stent crush due to aneurysm remodel, longitudinal or rotational movement, 
placement, fixation, or material fatigue and subsequent decreased kink resistance can result in branch 
vessel occlusion, lumen obstruction, end organ or limb ischemia.  These can be mitigated with the use of 
careful case planning for appropriate sizing, adherence to the investigational protocol, lining bridging stents 
with self-expanding stents to increase radial resistance, and regular follow-up.   
Barb fracture/separation due to placement, fixation, or fatigue can result in migration, separation, 
vascular trauma, or embolism.  This can be mitigated with the use of careful case planning for subject 
selection and regular follow-up.   
Fabric wear due to material fatigue can result in endoleak, component separation, or migration.  
Using proper placement of devices and regular follow-up, but fabric wear can still occur.   
Type III endoleak due to a defect in the graft or inadequate seal between modular graft components 
can lead to aneurysm enlargement, aneurysm rupture, or retrograde flow from branch arteries.  Although 
the risk can be mitigated with careful construction of the grafts, proper seal between grafts, completion 
angiograms, regular follow-ups, and treatment with secondary procedures or devices (cuffs, balloons, and 
stents), endoleaks can still occur.   
Biocompatibility risks due to use of materials that are not biocompatible can lead to adverse 
reactions in subjects.  This can be mitigated by only using commercially available materials that have 
acceptable biocompatibility profiles. Even with these mitigation strategies, adverse reactions can occur.   
4.5.2 Mitigation of Risks 
Significant care and thought has gone into designing the Valiant Thoracoabdominal Stent Graft 
System and investigational procedure for proper delivery and deployment of devices to minimize risks to 
patients to the greatest degree possible.  The design of the stent graft is bifurcated to provide flow to 
uninterrupted blood flow to the visceral and infrarenal segments during the repair process, negating the 
need for aortic clamping utilized in open repair.  Additionally, the design of the stent graft system is 
modular to allow for bailouts and staging of the procedure throughout device deployment.  At any point in 
the procedure, the patient still has the opportunity for alternative treatments such as open surgical repair or 
other endovascular techniques.   
All efforts will be made to minimize the identified risks including:  
• 
Adherence to eligibility criteria and screening procedures to ensure that appropriate 
patients are selected and enrolled. 

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• 
Adherence to the investigation protocol and clinical methods for case planning, 
device modification, and implantation will be followed.   
• 
Patients will be carefully monitored throughout the study period.  
• 
The investigator will evaluate the adverse events during the course of the study.   
Monitoring Procedures  
Study monitoring and auditing will be performed by experienced and appropriately trained 
personnel appointed by the sponsor/investigator to ensure that the investigation is conducted in accordance 
with FDA IDE regulations through the Johns Hopkins Office of Human Subjects Research (OHSR).  
Compliance Monitoring Specialists of the Johns Hopkins OHSR will conduct a monitoring visit for 
investigators holding an IDE to determine compliance with sponsor requirements in 21 CFR 812 before 
initiation of research.     
On-site monitoring for the study will be conducted and will be a continuous, interactive process to 
ensure that high-quality data are obtained in compliance with the clinical investigational plan and 
regulatory requirements.  A comprehensive review of case report forms will be performed to check for 
completeness and accuracy.  Accuracy of data reported on CRFs will be verified by comparison to source 
documents.  On-site monitoring will be frequent enough to assure continued acceptability of the data.  
Monitoring will occur at the following intervals: prior to the start of the clinical trial, at initiation of the 
study (at first implant and shortly thereafter with more frequent and intensive monitoring at the beginning 
of the study), at quarterly and/or interim periods and upon completion of the clinical study.  The monitor 
will oversee the progress of the investigation and may be an employee of the sponsor.  
Informed Consent 
• Review 100% of all informed consents to ensure: 
• That the subject signed and dated the informed consent form for him/herself. 
• A valid (current IRB-approved version) copy of consent form was used. 
• Review documentation of informed consent process. 
Protocol 
• Confirm that the study staff is conducting the study in compliance with the 
protocol approved by the IRB. 
Source Document Verification 
• Review first five subject charts for: 
• Trial eligibility.  If there are any subjects that did not meet trial eligibility, 
then five additional charts will be monitored.  These additional charts will be 
chosen randomly.   
• Primary and secondary safety and efficacy data- If there are 
discrepancies/errors discovered with reporting this data, then five additional 
charts will be monitored.  These additional charts will be chosen randomly.   
• Any correction made to the source documents is dated, initialed, and 
explained.  The original entry should not be obscured. 
• The protocol specific source documents are on file. 
• Source documents are completed in ink. 

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• Note to files are made for missing or incomplete data and to explain any 
discrepancies or additional comments. 
Electronic Case Report Forms and Electronic Data Capture 
Ensure the data reported on the eCRF is consistent with the source documents. 
• Discrepancies between the source documents and eCRF are explained in a 
note to file or captured in a comment in the eCRF. 
• Study team members will have access to Sanford’s electronic data capture 
system (EDC) and will export de-identified data originating from JHU to this 
centralized database which is hosted by NAMSA.  
 
Sanford’s central EDC was originally set-up as a data pooling mechanism to 
fulfil a CMS reimbursement requirement for parallel IDE sites using the same 
investigational device. Sanford is leading the effort now to aggregate de-
identified data from each independent IDE site. Sites can only access their 
specific data.  
 
NAMSA: Services provided by NAMSA includes EDC access and data table 
generation for annual progress reports to the FDA and interim analysis 
reports for DSMB meetings or any instances where patient safety signals may 
trigger an interim analysis or pooled data analysis for DSMB review. 
 
Sanford and Medtronic will have read-only access and will not have the 
ability to modify/edit eCRFs.  
Adverse Events & Serious Adverse Events 
• Monitor will review all subject research chart and medical records to ensure 
the following: 
• All AEs and SAEs have been reported including any abnormal physical exam 
findings determined to be clinically significant. 
• They have been reported in a timely manner defined as within ten (10) 
business days between the time the site staff became aware of the event to the 
time it has been recorded and entered in eCRF. 
• AEs have been reviewed; attribution has been assigned and signed by 
investigator in a timely manner. 
• Ensure any AEs and SAEs have been submitted to the IRB and FDA that 
meets IRB/FDA reporting criteria.  
• All subject deaths have been reported appropriately. 
Protocol Deviations 
• Ensure all protocol deviations that meet reporting requirements have been 
reported to the IRB as well as reported in eCRF. 
Investigational Product 
• Ensure investigational product has been properly handled and stored.   

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Reporting  
All reports to FDA will be identified as SI-IDE Reports: 
Deviations from the investigational plan:  The sponsor-investigator will notify the reviewing IRB 
and FDA of any deviation from the investigational plan to protect the life or physical well-being of 
a subject in an emergency. The notice will be provided as soon as possible but no later than 5 
working days after the emergency occurred. If the change or deviation may affect the scientific 
soundness of the investigational plan or the rights, safety or welfare of the subject, the sponsor will 
obtain prior IRB approval and also FDA approval for the deviation by submitting an 
IDE supplement. 
Unanticipated adverse device effects:  The sponsor-investigator will report the results of an 
evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs within 10 
working days after the sponsor-investigator first receives notice of the adverse effect. 
Withdrawal of IRB approval: The sponsor-investigator will notify FDA of the withdrawal of IRB 
approval of an investigation (or any part of an investigation) within 5 working days of receipt of the 
withdrawal of approval. 
Progress report or annual reports: The sponsor will provide progress reports to all reviewing 
IRBs and to the FDA using the suggested format provided at: 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/
InvestigationalDeviceExemptionIDE/ucm046717.htm#sugforforidefin 
To describe the follow-up compliance for the study, the sponsor will include a table in the 
annual progress report.  
Interim Reporting: As requested by the FDA, the sponsor will report at intervals of every five 
patients treated under the IDE regardless of study arm.  The interim report will be submitted within 
ten days following the 30-day follow-up of the fifth patient enrolled. 
 
Recalls and device dispositions:  
The sponsor-investigator will notify FDA and all reviewing IRB’s of any request that a sponsor-
investigator return, repair, or dispose of any unit of an investigational device. The notice will be made 
within 30 working days after the request is made and will state why the request was made. 
 
Final report: 
 The sponsor-investigator will notify FDA and all reviewing IRBs within 30 working days of the 
completion or termination of the investigation. The sponsor-investigator will also submit a final report to 
FDA and all reviewing IRBs and participating investigators within 6 months after the completion or 
termination of the investigation. The suggested format for final IDE reports will be utilized in preparing the 
final report as described at:  
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/
InvestigationalDeviceExemptionIDE/ucm046717.htm#sugforforidefin 
 

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Clinical Trial Database report:  
The sponsor-investigator with an applicable study registered with the National Institutes of Health (NIH) 
National Library of Medicine’s (NLM) ClinicalTrials.gov will report results of the study within 12 months 
of the trial reaching its completion data regardless of outcomes or if the study is terminated early.    
Failure to obtain informed consent:  
The sponsor-investigator will submit a report of the use of a device without first obtaining informed 
consent. The report will be made to FDA within 5 working days after receipt of the notice of such use. 
Other reports: 
 The sponsor-investigator will provide accurate, complete, and current information about any aspect 
of the investigation upon request from the reviewing IRB or FDA. 
 
 
Data and Safety Monitoring 
 This study will have oversight by Sanford Data Safety Monitoring Board (DSMB) consisting of 
independent scientific and bio-statistical expertise, who are not participating as investigators in the study.  
Sanford is an integrated healthcare system comprised of hospitals, physicians, and other healthcare 
providers and facilities located in Sioux Falls, SD. The Sanford DSMB will comprise at least 1 physician 
experienced in treating the study population and an independent biostatistician (including NAMSA 
statistical support).  The Sanford DSMB will work with the PI to monitor and evaluate the safety of 
subjects and progress of the study. The board will meet after every 5th patient receiving the investigational 
device and annually during the follow-up period to review subject data.  The board will also meet at 
unscheduled times according to clinical necessity. The data safety reports reviewed at each meeting will 
contain enrollment data and all documented adverse events experienced by the participants and treatment 
outcomes.  The focus of the analysis is to determine whether enrollment should continue or be closed and 
whether the trials should continue as originally designed or require modification/amendment.  
 
 
Definitions 
Aortic aneurysm enlargement: >5mm as compared to any previous CT measure using orthogonal (i.e., 
perpendicular to the centerline) measurements  
Aortoiliac aneurysm: aneurysm of the abdominal aorta and including one or both of the iliac arteries  
Aneurysm-related mortality: 
Death occurring within 30 days or during hospitalization following the index procedure, unless 
there is evidence of accidental or self-inflicted death; 
Death occurring within 30 days or during hospitalization following conversion to open repair or a 
secondary intervention for migration, Type I and III endoleaks, device integrity failure (e.g., 
fracture), or patency-related events (i.e., device stenosis or occlusion and embolic events), unless 
there is evidence of accidental or self-inflicted death;  
Death occurring within 30 days or during hospitalization for a complication of the aneurysm or a 
complication associated with the device, such as:  
• aortic rupture 
• fistula formation (e.g., aorto-enteric) 
• embolization 
• malperfusion of organ(s) or limb(s) 

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Arterial fistula formation: formation of an abnormal connection or passageway between an artery and 
adjacent structures 
Conversion to Open, Early: any open repair within 30 days of the index procedure involving the 
vasculature in the abdomen and/or pelvis. 
Conversion to Open, Late: any open surgical repair involving stentgraft removal after 30days post index 
procedure 
Chronic Obstructive Pulmonary Disease (COPD): forced expiratory volume (FEV1) < 1.0 liter or 
receiving home oxygen  
Crawford Type IV TAAA: aneurysmal dilatation originating within 5cm of the celiac artery 
Disabling stroke: Modified Rankin Score MRS >2 
Distal landing zone: aortic fixation site furthest from the heart  
Embolization: dislodging of an upstream particle that travels downstream causing blockage of free flow 
further downstream. Embolization could result in malperfusion 
Embolus: blood clot that forms at one location (presumably from the aneurysmal sac, aortic neck, or 
adjacent vessels) and is dislodged to another location resulting in ischemic changes  
Emergent:  an aneurysm requiring immediate treatment 
Endoleak:  
Type I: leak occurring at the proximal or distal fixation site, including leakage around fenestrations  
Type Ia: leak occurring at the proximal fixation zone of the stent-graft  
Type Ib: leak occurring at the distal fixation zone of the stent graft  
Type Ic: leak occurring at the distal fixation zone of the covered stents in the visceral vessels 
incorporated by the fenestrations  
Type II: leak caused by retrograde flow from patent lumbar or inferior mesenteric arteries  
Type IIIa: leak caused by a defect in the graft fabric 
 Type IIIb: leak caused by inadequate seal between modular graft components  
Type IV:  leak caused by graft fabric porosity, often resulting in a generalized blush of contrast 
within the aneurysm sac  
Type V: aneurysm enlargement without visualized leak 
 
Endoleak, Early: any endoleak observed within 30 days after device deployment  

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Endoleak, Late: any endoleak observed later than 30 days after deployment that was not documented 
during the first 30 days after deployment  
Estimated Glomerular Filtration Rate (eGFR): estimated GFR (mL/min/1.73 m2) = 175 x (Serum 
creatinine)-1.154 x (Age)-0.203x (0.743 if female) x (1.210 if African-American)  
Graft Relining: placement of the investigational system that results in landing zones that extend beyond 
the limits of the previously placed graft material 
Limb occlusion: the presence of thrombus within any graft limb that creates occlusion  
Major adverse events: all-cause mortality, bowel ischemia (requiring medical or surgical management), 
myocardial infarction, paraplegia, renal failure, respiratory failure, and stroke 
• All-Cause Mortality: any death occurring within the first 30 days post procedure 
• Bowel Ischemia: Bowel ischemia due to limb or arterial occlusion, graft placement, or 
embolization. 
• Myocardial infarction: raised levels of cardiac biomarkers or ECG changes  
• Paraplegia: spinal cord ischemic event resulting in complete loss of motor function with or without 
loss of sensation in the lower extremities 
• results in a serum creatinine >2.0 mg/dl that does not spontaneously resolve  
• Renal Failure: acute or progressive renal insufficiency leading to the need for dialysis or 
hemofiltration 
• Respiratory failure: ventilator support >24 hours after spinal drain removal and/or reintubation.  
This definition does not put the patient at any increased risk.  The high risk patient population being 
treated in this study is prone to pre-existing comorbidities, including COPD and decreased 
respiratory function, and may require extended ventilator support while in the supine position for 
spinal drainage.   
• Stroke: neurological deficit that lasts > 24 hours 
Malperfusion of organ(s) or limb(s): loss of flow through a particular vascular bed has been partially or 
completely compromised leaving the said organ or limb ischemic 
Migration, clinically significant: antegrade or retrograde migration that requires surgical or endovascular 
intervention 
 
Paraparesis: spinal cord ischemic event resulting in partial neurologic deficit in the lower extremities 
Parietal arteries (branches): inferior phrenic, lumbars and middle sacral arteries  
 
Patency: the state of a vessel that has unimpeded flow into and out of the vessel   
Proximal landing zone: the aortic fixation site closest to the heart 
Proximal fixation length: the aortic fixation site measured from the proximal edge of the graft to the start 
of the aneurysm  

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Renal insufficiency: rise in serum creatinine of more than 50% above pre-procedure level which results in 
a serum creatinine >2.0 mg/dl that does not spontaneously resolve  
 
Technical success:   
• successful delivery (i.e., ability to deliver the implant to the intended implantation site, 
without the need for unanticipated  corrective intervention related to delivery); 
• successful  and accurate deployment, defined as: 
▪ deployment of the endovascular stent-graft at the intended implantation site; 
▪ patency of all endovascular graft and stent components; absence of device 
deformations (e.g., kinks, stent eversion, mal-deployment, misaligned 
deployment) requiring unplanned placement of an additional device;  
▪ absence of inadvertent covering of aortic branch vessels; and 
• successful withdrawal (i.e., successful withdrawal of the delivery system, without need 
for unanticipated  corrective intervention related to withdrawal) 
Thrombus: a blood clot that forms due to injury of a vessel. If the thrombus becomes dislodged and travels 
it is referred to as an embolus  
Treatment success:  a composite of technical success and freedom from the following: 
• aneurysm enlargement i.e. >5-mm as compared to any previous CT measuring orthogonal (i.e., 
perpendicular to centerline) measurements 
• aneurysm-related mortality 
• aneurysm rupture 
• conversion to open repair 
• secondary intervention for migration, type I and III endoleaks, device integrity failure (i.e., 
fracture), and patency-related events (i.e., device stenosis or occlusion and embolic events) 
• Renal failure 
 
Type B – Chronic Dissection:  a dissection that takes off distal to the left subclavian artery that is greater 
than 30 days old 
Type B – Subacute Dissection:  a dissection that takes of distal to the left subclavian artery that is 15-30 
days old 
Urgent:  An aneurysm requiring repair within 1 week 
Visceral arteries (branches): celiac, superior mesenteric, inferior mesenteric, renal arteries 
 
9. Benefits 
a. 
Description of the probable benefits for the participant and for society. 
To find potential benefits after complex aortic surgery for patient outcomes and health. 
 

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10. Payment and Remuneration 
a. 
Detail compensation for participants including possible total compensation, proposed bonus, 
and any proposed reductions or penalties for not completing the protocol. 
Participants will not receive payment/remuneration. 
 
11. Costs 
a. 
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them. 
There is no cost to participate in the study. The procedures are covered under guidelines for 
Medicare/Medicaid in the standard delivery of care. 
 
Medicare Generalizability  
The Valiant Thoracoabdominal Stent Graft System is intended to treat thoracoabdominal aortic 
aneurysms and the highest incidence of this disease is observed in Medicare eligible patients.  A 2013 
market survey of inpatient data revealed that 79.8% (1642/2058) of all thoracoabdominal aortic aneurysms 
occurred in patients over the age of 65.  In that same survey, Medicare was the principal payer in 76.3% of 
those cases and the secondary payer in 82.6% of those cases58.   
Aneurysmal degeneration occurs more commonly in the aging population.  Aging may lead to 
weakening of the aortic wall due to changes in the collagen and elastin. Additionally, comorbidities that 
may increase the risk for aneurysm formation are smoking, chronic obstructive, pulmonary disease, 
hypertension, atherosclerosis, male gender, older age, high body mass, genetic disorders, and family 
history87.   
 
 
 
 

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1. 
Standring S. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 40th Edition. Churchill-Livingstone, 
Elsevier; 2008. 
2. 
Dapunt OE, Galla JD, Sadeghi AM, et al. The natural history of thoracic aortic aneurysms. The Journal of 
thoracic and cardiovascular surgery. 1994;107(5):1323-1332; discussion 1332-1323. 
3. 
Cambria RA, Gloviczki P, Stanson AW, et al. Outcome and expansion rate of 57 thoracoabdominal aortic 
aneurysms managed nonoperatively. American journal of surgery. 1995;170(2):213-217. 
4. 
cronenwett JL SS, Wall MH. Variables that affect the expansion rate and outcome of small abdominal aortic 
aneurysms. Journal of vascular surgery. 1990;11:260-269. 
5. 
Cronenwett JL, Murphy TF, Zelenock GB, et al. Actuarial analysis of variables associated with rupture of 
small abdominal aortic aneurysms. Surgery. 1985;98(3):472-483. 
6. 
Bickerstaff LK, Pairolero PC, Hollier LH, et al. Thoracic aortic aneurysms: a population-based study. Surgery. 
1982;92(6):1103-1108. 
7. 
McNamara JJ, Pressler VM. Natural history of arteriosclerotic thoracic aortic aneurysms. The Annals of 
thoracic surgery. 1978;26(5):468-473. 
8. 
Pressler V, McNamara JJ. Thoracic aortic aneurysm: natural history and treatment. The Journal of thoracic 
and cardiovascular surgery. 1980;79(4):489-498. 
9. 
Crawford ES, DeNatale RW. Thoracoabdominal aortic aneurysm: observations regarding the natural course 
of the disease. Journal of vascular surgery. 1986;3(4):578-582. 
10. 
Moreno-Cabral CE, Miller DC, Mitchell RS, et al. Degenerative and atherosclerotic aneurysms of the thoracic 
aorta. Determinants of early and late surgical outcome. The Journal of thoracic and cardiovascular surgery. 
1984;88(6):1020-1032. 
11. 
de Bakey ME, McCollum CH, Graham JM. Surgical treatment of aneurysms of the descending thoracic aorta: 
long-term results in 500 patients. The Journal of cardiovascular surgery. 1978;19(6):571-576. 
12. 
Cooke JC, Cambria RP. Simultaneous tracheobronchial and esophageal obstruction caused by a descending 
thoracic aneurysm. Journal of vascular surgery. 1993;18(1):90-94. 
13. 
Assar AN, Zarins CK. Ruptured abdominal aortic aneurysm: a surgical emergency with many clinical 
presentations. Postgraduate medical journal. 2009;85(1003):268-273. 
14. 
Zanetti PP, Krasoń M, Walas R, et al. “Open” repair of ruptured thoracoabdominal aortic aneurysm 
(experience of 51 cases). Kardiochirurgia i Torakochirurgia Polska = Polish Journal of Cardio-Thoracic 
Surgery. 2015;12(2):119-125. 
15. 
Gkremoutis A, Schmandra T, Meyn M, Schmitz-Rixen T, Keese M. Hybrid Approach to Emergent and Urgent 
Treatment of Complex Thoracoabdominal Aortic Pathology. European Journal of Vascular and Endovascular 
Surgery. 2014;48(4):407-413. 
16. 
Norwood MGA, Polimenovi NM, Sutton AJ, Bown MJ, Sayers RD. Abdominal Aortic Aneurysm Repair in 
Patients with Chronic Renal Disease. European Journal of Vascular and Endovascular Surgery.27(3):287-291. 
17. 
Guntani A, Okadome J, Kawakubo E, et al. Clinical Results of Endovascular Abdominal Aortic Aneurysm 
Repair in Patients with Renal Insufficiency without Hemodialysis. Annals of Vascular Diseases. 
2012;5(2):166-171. 
18. 
Afifi RO, Sandhu HK, Trott AE, et al. Redo Thoracoabdominal Aortic Aneurysm Repair: A Single-Center 
Experience Over 25&#xa0;Years. The Annals of thoracic surgery. 
19. 
Tshomba Y, Melissano G, Chiesa R. Redo Open and Endovascular Procedures after Open Thoraco-
Abdominal Aortic Aneurysm Repair. In: Chiesa R, Melissano G, Zangrillo A, eds. Thoraco-Abdominal Aorta: 
Surgical and Anesthetic Management. Milano: Springer Milan; 2011:523-539. 
20. 
Verhoeven ELG, Muhs BE, Zeebregts CJAM, et al. Fenestrated and Branched Stent-grafting After Previous 
Surgery Provides a Good Alternative to Open Redo Surgery. European Journal of Vascular and Endovascular 
Surgery. 2007;33(1):84-90. 
21. 
Piazza M, Ricotta JJ, 2nd. Open surgical repair of thoracoabdominal aortic aneurysms. Annals of vascular 
surgery. 2012;26(4):600-605. 
22. 
Rectenwald JE, Huber TS, Martin TD, et al. Functional outcome after thoracoabdominal aortic aneurysm 
repair. Journal of vascular surgery. 2002;35(4):640-647. 

Date: June 30, 2020    
Principal Investigator: James Black 
Application Number: IRB00075706 
 
Version 4.0 
Page 51 of 54 
 
23. 
Schepens MA, Heijmen RH, Ranschaert W, Sonker U, Morshuis WJ. Thoracoabdominal aortic aneurysm 
repair: results of conventional open surgery. European journal of vascular and endovascular surgery : the 
official journal of the European Society for Vascular Surgery. 2009;37(6):640-645. 
24. 
Wong DR, Parenti JL, Green SY, et al. Open repair of thoracoabdominal aortic aneurysm in the modern 
surgical era: contemporary outcomes in 509 patients. Journal of the American College of Surgeons. 
2011;212(4):569-579; discussion 579-581. 
25. 
Bensley RP, Curran T, Hurks R, et al. Open repair of intact thoracoabdominal aortic aneurysms in the 
American College of Surgeons National Surgical Quality Improvement Program. Journal of vascular surgery. 
2013;58(4):894-900. 
26. 
Nathan DP, Brinster CJ, Woo EY, Carpenter JP, Fairman RM, Jackson BM. Predictors of early and late 
mortality following open extent IV thoracoabdominal aortic aneurysm repair in a large contemporary 
single-center experience. Journal of vascular surgery. 2011;53(2):299-306. 
27. 
Menard MT, Nguyen LL, Chan RK, et al. Thoracovisceral segment aneurysm repair after previous infrarenal 
abdominal aortic aneurysm surgery. Journal of vascular surgery. 2004;39(6):1163-1170. 
28. 
Coselli JS, Bozinovski J, LeMaire SA. Open surgical repair of 2286 thoracoabdominal aortic aneurysms. The 
Annals of thoracic surgery. 2007;83(2):S862-864; discussion S890-862. 
29. 
Tabayashi K, Saiki Y, Kokubo H, et al. Protection from postischemic spinal cord injury by perfusion cooling of 
the epidural space during most or all of a descending thoracic or thoracoabdominal aneurysm repair. 
General thoracic and cardiovascular surgery. 2010;58(5):228-234. 
30. 
Messe SR, Bavaria JE, Mullen M, et al. Neurologic outcomes from high risk descending thoracic and 
thoracoabdominal aortic operations in the era of endovascular repair. Neurocritical care. 2008;9(3):344-
351. 
31. 
Coselli JS, LeMaire SA, Miller CC, 3rd, et al. Mortality and paraplegia after thoracoabdominal aortic 
aneurysm repair: a risk factor analysis. The Annals of thoracic surgery. 2000;69(2):409-414. 
32. 
Archer W, Hoch, and Kranner. Cardiac function is a risk factor for paralysis in thoracoabdominal aortic 
replacement. Journal of vascular surgery. 1998;27(5):821-830. 
33. 
Greenberg RK, Lu Q, Roselli EE, et al. Contemporary analysis of descending thoracic and thoracoabdominal 
aneurysm repair: a comparison of endovascular and open techniques. Circulation. 2008;118(8):808-817. 
34. 
Safi HJ, Estrera AL, Azizzadeh A, Coogan S, Miller CC, 3rd. Progress and future challenges in 
thoracoabdominal aortic aneurysm management. World journal of surgery. 2008;32(3):355-360. 
35. 
Cambria RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: 
results with 337 operations performed over a 15-year interval. Annals of surgery. 2002;236(4):471-479; 
discussion 479. 
36. 
Andersen ND, Keenan JE, Ganapathi AM, Gaca JG, McCann RL, Hughes GC. Current management and 
outcome of chronic type B aortic dissection: results with open and endovascular repair since the advent of 
thoracic endografting. Annals of cardiothoracic surgery. 2014;3(3):264-274. 
37. 
Chou H-P, Chang H-T, Chen C-K, et al. Outcome comparison between thoracic endovascular and open repair 
for type B aortic dissection: A population-based longitudinal study. Journal of the Chinese Medical 
Association.78(4):241-248. 
38. 
Arya S, Coleman DM, Knepper J, et al. Outcomes after late explantation of aortic endografts depend on 
indication for explantation. Ann Vasc Surg. 2013;27(7):865-873. 
39. 
Moulakakis KG, Dalainas I, Mylonas S, Giannakopoulos TG, Avgerinos ED, Liapis CD. Conversion to open 
repair after endografting for abdominal aortic aneurysm: a review of causes, incidence, results, and surgical 
techniques of reconstruction. J Endovasc Ther. 2010;17(6):694-702. 
40. 
Katsargyris A, Oikonomou K, Spinelli D, Houthoofd S, Verhoeven EL. Fenestrated and branched stent-
grafting after previous open or endovascular aortic surgery. J Cardiovasc Surg (Torino). 2014;55(2 Suppl 
1):95-103. 
41. 
Dorsey C, Chandra V, Lee JT. The "Terrace Technique"-Totally Endovascular Repair of a Type IV 
Thoracoabdominal Aortic Aneurysm. Annals of vascular surgery. 2014. 

Date: June 30, 2020    
Principal Investigator: James Black 
Application Number: IRB00075706 
 
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Page 52 of 54 
 
42. 
Cariati M, Mingazzini P, Dallatana R, Rossi UG, Settembrini A, Santuari D. Endovascular treatment of a 
symptomatic thoracoabdominal aortic aneurysm by chimney and periscope techniques for total visceral 
and renal artery revascularization. Cardiovascular and interventional radiology. 2014;37(1):251-256. 
43. 
Cariati M, Rossi UG. Letter REPLY Re: "Endovascular Treatment of a Symptomatic Thoracoabdominal Aortic 
Aneurysm by Chimney and Periscope Techniques for Total Visceral and Renal Artery Revascularization". 
Cardiovascular and interventional radiology. 2014. 
44. 
Pecoraro F, Pfammatter T, Mayer D, et al. Multiple periscope and chimney grafts to treat ruptured 
thoracoabdominal and pararenal aortic aneurysms. Journal of endovascular therapy : an official journal of 
the International Society of Endovascular Specialists. 2011;18(5):642-649. 
45. 
Scali ST, Feezor RJ, Chang CK, et al. Critical analysis of results after chimney endovascular aortic aneurysm 
repair raises cause for concern. Journal of vascular surgery. 2014. 
46. 
Moulakakis KG, Mylonas SN, Avgerinos E, et al. The chimney graft technique for preserving visceral vessels 
during endovascular treatment of aortic pathologies. Journal of vascular surgery. 2012;55(5):1497-1503. 
47. 
Kasirajan K. Branched grafts for thoracoabdominal aneurysms: off-label use of FDA-approved devices. 
Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists. 
2011;18(4):471-476. 
48. 
Lobato AC, Camacho-Lobato L. A new technique to enhance endovascular thoracoabdominal aortic 
aneurysm therapy--the sandwich procedure. Seminars in vascular surgery. 2012;25(3):153-160. 
49. 
Oderich GS, Ricotta JJ, 2nd. Modified fenestrated stent grafts: device design, modifications, implantation, 
and current applications. Perspectives in vascular surgery and endovascular therapy. 2009;21(3):157-167. 
50. 
Oderich GS, Fatima J, Gloviczki P. Stent graft modification with mini-cuff reinforced fenestrations for urgent 
repair of thoracoabdominal aortic aneurysms. Journal of vascular surgery. 2011;54(5):1522-1526. 
51. 
Haulon S, Greenberg RK. Part Two: Treatment of type IV thoracoabdominal aneurysms--fenestrated stent-
graft repair is now the best option. European journal of vascular and endovascular surgery : the official 
journal of the European Society for Vascular Surgery. 2011;42(1):4-8. 
52. 
Oderich GS, Mendes BC, Correa MP. Preloaded guidewires to facilitate endovascular repair of 
thoracoabdominal aortic aneurysm using a physician-modified branched stent graft. Journal of vascular 
surgery. 2014;59(4):1168-1173. 
53. 
Benjelloun A, Henry M, Ghannam A, et al. Endovascular treatment of a tuberculous thoracoabdominal 
aneurysm with the Multilayer stent. Journal of endovascular therapy : an official journal of the International 
Society of Endovascular Specialists. 2012;19(1):115-120. 
54. 
Vaislic CD, Fabiani JN, Chocron S, et al. One-year outcomes following repair of thoracoabdominal 
aneurysms with the multilayer flow modulator: report from the STRATO trial. Journal of endovascular 
therapy : an official journal of the International Society of Endovascular Specialists. 2014;21(1):85-95. 
55. 
Sultan S, Hynes N. One-year results of the multilayer flow modulator stent in the management of 
thoracoabdominal aortic aneurysms and type B dissections. Journal of endovascular therapy : an official 
journal of the International Society of Endovascular Specialists. 2013;20(3):366-377. 
56. 
Lazaris AM, Maheras AN, Vasdekis SN. A multilayer stent in the aorta may not seal the aneurysm, thereby 
leading to rupture. Journal of vascular surgery. 2012;56(3):829-831. 
57. 
Ferrero E, Gibello L, Ferri M, Viazzo A, Nessi F. Aortic arch rupture after multiple multilayer stent treatment 
of a thoracoabdominal aneurysm. Journal of vascular surgery. 2013. 
58. 
Cavalcante RN, Nishinari K, Yazbek G, Krutman M, Bomfim G, Wolosker N. Severe visceral ischemia and 
death after multilayer stent deployment for the treatment of a thoracoabdominal aortic aneurysm. Journal 
of vascular surgery. 2014. 
59. 
de Vries JP. Treatment of complex thoracoabdominal or juxtarenal aortic aneurysms with a Multilayer 
stent. Journal of endovascular therapy : an official journal of the International Society of Endovascular 
Specialists. 2012;19(1):125-127. 
60. 
Sherif Sultan NH, and Mohamed Sultan. When not to implant the multilayer flow modulator: lessons 
learned from application outside the indications for use in patients wtih thoracoabdominal pathologies. 
Journal of Endovascular Therapy. 2014;21:96-112. 

Date: June 30, 2020    
Principal Investigator: James Black 
Application Number: IRB00075706 
 
Version 4.0 
Page 53 of 54 
 
61. 
Bin Jabr A, Lindblad B, Dias N, Resch T, Malina M. Efficacy and durability of the chimney graft technique in 
urgent and complex thoracic endovascular aortic repair. J Vasc Surg. 2015;61(4):886-894 e881. 
62. 
Filippi F, Ficarelli R, Tirotti C, Stella N, Taurino M. Emergent fully endovascular treatment of a free ruptured 
thoracoabdominal aneurysm. Ann Vasc Surg. 2015;29(4):842 e849-813. 
63. 
Marino M, Kasemi H, Di Angelo CL, Fadda GF. Ruptured thoracoabdominal aneurysm treatment with 
modified chimney stent graft. Ann Thorac Surg. 2014;98(2):e37-40. 
64. 
Schlosser FJ, Aruny JE, Freiburg CB, Mojibian HR, Sumpio BE, Muhs BE. The chimney procedure is an 
emergently available endovascular solution for visceral aortic aneurysm rupture. J Vasc Surg. 
2011;53(5):1386-1390. 
65. 
Clouse WD, Hallett JW, Jr., Schaff HV, et al. Acute aortic dissection: population-based incidence compared 
with degenerative aortic aneurysm rupture. Mayo Clinic proceedings. 2004;79(2):176-180. 
66. 
Mehta RH, Manfredini R, Hassan F, et al. Chronobiological patterns of acute aortic dissection. Circulation. 
2002;106(9):1110-1115. 
67. 
Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. European heart journal. 
2001;22(18):1642-1681. 
68. 
Thrumurthy SG, Karthikesalingam A, Patterson BO, Holt PJ, Thompson MM. The diagnosis and management 
of aortic dissection. Bmj. 2012;344:d8290. 
69. 
Eggebrecht H, Nienaber CA, Neuhauser M, et al. Endovascular stent-graft placement in aortic dissection: a 
meta-analysis. European heart journal. 2006;27(4):489-498. 
70. 
Kim KM, Donayre CE, Reynolds TS, et al. Aortic remodeling, volumetric analysis, and clinical outcomes of 
endoluminal exclusion of acute complicated type B thoracic aortic dissections. Journal of vascular surgery. 
2011;54(2):316-324; discussion 324-315. 
71. 
Yang CP, Hsu CP, Chen WY, et al. Aortic remodeling after endovascular repair with stainless steel-based 
stent graft in acute and chronic type B aortic dissection. Journal of vascular surgery. 2012;55(6):1600-1610. 
72. 
Andacheh ID, Donayre C, Othman F, Walot I, Kopchok G, White R. Patient outcomes and thoracic aortic 
volume and morphologic changes following thoracic endovascular aortic repair in patients with complicated 
chronic type B aortic dissection. Journal of vascular surgery. 2012;56(3):644-650; discussion 650. 
73. 
Mani K, Clough RE, Taylor PR. Regarding "patient outcomes and thoracic aortic volume and morphologic 
changes following thoracic endovascular aortic repair in patients with complicated chronic type B aortic 
dissection". Journal of vascular surgery. 2013;57(3):898. 
74. 
Liewald F, Kapfer X, Gorich J, Halter G, Tomczak R, Scharrer-Pamler R. Endograft treatment of anastomotic 
aneurysms following conventional open surgery for infrarenal aortic aneurysms. European journal of 
vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 
2001;21(1):46-50. 
75. 
O'Callaghan A, Mastracci TM, Eagleton MJ. Staged endovascular repair of thoracoabdominal aortic 
aneurysms limits incidence and severity of spinal cord ischemia. Journal of vascular surgery. 
2015;61(2):347-354.e341. 
76. 
Banga PV, Oderich GS, Reis de Souza L, et al. Neuromonitoring, Cerebrospinal Fluid Drainage, and Selective 
Use of Iliofemoral Conduits to Minimize Risk of Spinal Cord Injury During Complex Endovascular Aortic 
Repair. Journal of endovascular therapy : an official journal of the International Society of Endovascular 
Specialists. 2016;23(1):139-149. 
77. 
Fratesi F, Handa A, Uberoi R, Sideso E. Chimney-Graft as a Bail-Out Procedure for Endovascular Treatment 
of an Inflammatory Juxtarenal Abdominal Aortic Aneurysm. Case reports in vascular medicine. 
2015;2015:531017. 
78. 
Oderich GS, Mendes BC, Kanamori KS. Technique of implantation and bail-out maneuvers for endovascular 
fenestrated repair of juxtarenal aortic aneurysms. Perspectives in vascular surgery and endovascular 
therapy. 2013;25(1-2):28-37. 
79. 
Roselli EE, Greenberg RK, Pfaff K, Francis C, Svensson LG, Lytle BW. Endovascular treatment of 
thoracoabdominal aortic aneurysms. The Journal of thoracic and cardiovascular surgery.133(6):1474-
1482.e1471. 

Date: June 30, 2020    
Principal Investigator: James Black 
Application Number: IRB00075706 
 
Version 4.0 
Page 54 of 54 
 
80. 
Goodney PP, Travis L, Lucas FL, et al. Survival After Open Versus Endovascular Thoracic Aortic Aneurysm 
Repair in an Observational Study of the Medicare Population. Circulation. 2011;124(24):2661-2669. 
81. 
Conrad MF, Ergul EA, Patel VI, Paruchuri V, Kwolek CJ, Cambria RP. Management of Diseases of the 
Descending Thoracic Aorta in the Endovascular Era: A Medicare Population Study. Annals of surgery. 
2010;252(4):603-610. 
82. 
Suess T, Anderson J, Danielson L, et al. Examination of near-wall hemodynamic parameters in the renal 
bridging stent of various stent graft configurations for repairing visceral branched aortic aneurysms. Journal 
of vascular surgery. 2016;64(3):788-796. 
83. 
Mohabbat W, Greenberg RK, Mastracci TM, Cury M, Morales JP, Hernandez AV. Revised duplex criteria and 
outcomes for renal stents and stent grafts following endovascular repair of juxtarenal and 
thoracoabdominal aneurysms. Journal of vascular surgery. 2009;49(4):827-837; discussion 837. 
84. 
Registry. BSfETatGCoAS-GTfARG. Early results of fenestrated endovascular repair of juxtarenal aortic 
aneurysms in the United Kingdom. Circulation. 2012;125(22):2707-2715. 
85. 
Greenberg R, Eagleton M, Mastracci T. Branched endografts for thoracoabdominal aneurysms. The Journal 
of thoracic and cardiovascular surgery. 2010;140(6 Suppl):S171-178. 
86. 
Chuter TA, Rapp JH, Hiramoto JS, Schneider DB, Howell B, Reilly LM. Endovascular treatment of 
thoracoabdominal aortic aneurysms. Journal of vascular surgery. 2008;47(1):6-16. 
87. 
Frederick JR, Woo YJ. Thoracoabdominal aortic aneurysm. Annals of cardiothoracic surgery. 2012;1(3):277-
285.