25
5.2 Potential Adverse Events
Adverse events that may occur and/or require intervention include, but are
not limited to:
• Amputation
• Anesthetic complications and subsequent attendant problems (e.g.,
aspiration)
• Aneurysm enlargement
• Aneurysm rupture and death
• Aortic damage, including perforation, dissection, bleeding, rupture and
death
• Arterial or venous thrombosis and/or pseudoaneurysm
• Arteriovenous fistula
• Bleeding, hematoma or coagulopathy
• Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis)
• Cardiac complications and subsequent attendant problems (e.g.,
arrhythmia, myocardial infarction, congestive heart failure, hypotension,
hypertension)
• Claudication (e.g., buttock, lower limb)
• Death
• Edema
• Embolization (micro and macro) with transient or permanent ischemia or
infarction
• Endoleak
• Endoprosthesis: improper component placement; incomplete component
deployment; component migration; suture break; occlusion; infection; stent
fracture; graft material wear; dilatation; erosion; puncture; perigraft flow;
barb separation and corrosion
• Fever and localized inflammation
• Genitourinary complications and subsequent attendant problems (e.g.,
ischemia, erosion, fistula, incontinence, hematuria, infection)
• Graft or native vessel occlusion
• Hepatic failure
• Impotence
• Infection of the aneurysm, device or access site, including abscess
formation, transient fever and pain
• Lymphatic complications and subsequent attendant problems (e.g., lymph
fistula)
• Neurologic local or systemic complications and subsequent attendant
problems (e.g., stroke, transient ischemic attack, paraplegia, paraparesis,
paralysis)
• Pulmonary/respiratory complications and subsequent attendant problems
(e.g., pneumonia, respiratory failure, prolonged intubation)
• Renal complications and subsequent attendant problems (e.g., artery
occlusion, contrast toxicity, insufficiency, failure)
• Surgical conversion to open repair
• Vascular access site complications, including infection, pain, hematoma,
pseudoaneurysm, arteriovenous fistula
• Vascular spasm or vascular trauma (e.g., iliofemoral vessel dissection,
bleeding, rupture, death)
• Vessel damage
• Wound complications and subsequent attendant problems (e.g.,
dehiscence, infection)
Device Related Adverse Event Reporting
Any adverse event (clinical incident) involving the Zenith Flex AAA
Endovascular Graft should be reported to COOK immediately. For customers
in the United States, to report an incident, call the Customer Relations
Department at 1-800-457-4500 (24-hour) or 1-812-339-2235. For customers
outside the United States, please call your distributor.
6 SUMMARY OF CLINICAL STUDIES
6.1 Objectives
The primary objective of the clinical study was to evaluate the safety and
effectiveness of a previous version of the device (Zenith AAA Endovascular
Graft) as an alternative to open surgical repair in the primary treatment of
infrarenal abdominal aortic aneurysms. Study hypotheses examined whether
standard risk patients experienced less 30-day morbidity, non-inferior 30-day
survival rates, non-inferior 12-month survival rates, non-inferior 12-month
treatment success and improved clinical utility measures compared to surgical
control patients. Safety was determined by evaluating whether the Zenith
AAA Endovascular Graft subjects would have reduced 30-day morbidity,
non-inferior 30-day and 12-month survival and non-inferior 12-month
treatment success compared to the subjects treated with open surgical
treatment. Effectiveness was based on exclusion of the aneurysm including
the absence of any endoleak, the absence of aneurysm enlargement (≥5 mm)
and the absence of major device adverse events evaluated through one year
follow-up. Secondary objectives included an assessment of clinical benefit
and quality-of-life measures.
6.2 Study Design
The U.S. clinical study was a multicenter, nonrandomized study comparing
standard medical risk patients who received an endovascular graft to an
open surgical control. There were two additional study arms for high medical
risk and roll-in treatment groups. Fifteen centers enrolled 200 standard risk,
80 surgical control, 100 high risk and 52 roll-in patients. The control group
included patients whose vascular anatomy may not have been suitable for
endovascular AAA repair. Follow-up evaluations were scheduled for
pre-discharge, 1 month, 6 months, 12 months and 24 months. Patient follow-
up and accountability at 1 month, 12 months and 24 months are presented
in Table 6.2.1 as these were the primary data analysis time points. Imaging
data provided in this summary are based on findings from an independent
centralized image analysis laboratory (Core Lab) which reviewed CT scans and
abdominal X-rays to assess aneurysm diameter changes, device and relative
component migration, device integrity (wire and graft) and the presence and
type of endoleaks. Clinical events were adjudicated by an independent clinical
events committee and safety was monitored by a data safety monitoring
committee.
Surgical and Zenith standard risk patients met identical pathophysiologic risk
criteria. The endovascular groups excluded circumferential thrombus in the
proximal neck, proximal neck less than 15 mm in length, outer wall to outer
wall proximal neck diameter less than 18 mm or greater than 28 mm, severe
proximal neck angulation, outer wall to outer wall iliac artery diameter less
than 7.5 mm or greater than 20 mm at distal fixation site or iliac artery distal
fixation site less than 10 mm in length.
Patients were considered at higher risk for surgical repair if they had age
greater than 80, baseline creatinine >2.0 mg/dl, home oxygen therapy, FEV
1
<1 liter, ejection fraction <25%, disabling COPD, New York Heart Classification
3 or 4, hostile abdomen, dialysis, MI within last 6 months, medically intractable
hypertension, previous stroke with residual deficit, cultural objection
to receipt of blood or blood products, previous renal bypass surgery or
inflammatory aneurysm.
Before enrolling patients into the pivotal trial, centers without Zenith AAA
Endovascular Graft experience were required to treat initial patients under the
supervision of a proctor. These roll-in patients were a combination of standard
and high risk patients and were followed according to the same schedule as
the patients in the pivotal trial.
Table 5.1.2 Adverse Events
1
in Clinical Study
Zenith Standard Risk
Surgical Standard Risk
P
value
Zenith High Risk
Zenith Roll-in
Freedom from Morbidity
(0-30 days)
80%
(160/200)
58%
(46/80)
<.001
68%
(68/100)
73%
(38/52)
Cardiovascular
2
3.0%
(6/200)
11%
(9/80)
.02
14%
(14/100)
1.9%
(1/52)
Pulmonary
3
1.0%
(2/200)
15%
(12/80)
<.001
2.0%
(2/100)
0.0%
(0/52)
Renal
4, 9
2.5%
(5/200)
10%
(8/80)
.01
6.0%
(6/100)
5.8%
(3/52)
Bowel
5
1.0%
(2/200)
3.8%
(3/80)
.14
1.0%
(1/100)
1.9%
(1/52)
Wound
6
4.5%
(9/200)
7.5%
(6/80)
.38
2.0%
(2/100)
3.8%
(2/52)
Neurologic
7
0.0%
(0/200)
2.5%
(2/80)
.08
0.0%
(0/100)
0.0%
(0/52)
Vascular
8,11
11%
(21/200)
31%
(25/80)
<.001
20%
(20/100)
19%
(10/52)
Freedom from Morbidity
(31-365 days)
91%
(181/198)
86%
(67/78)
.25
79%
(77/98)
86%
(44/51)
Cardiovascular
2
2.5%
(5/198)
3.8%
(3/78)
.69
5.1%
(5/98)
2.0%
(1/51)
Pulmonary
3
0.5%
(1/198)
1.3%
(1/78)
.49
4.1%
(4/98)
0.0%
(0/51)
Renal
4, 10
0.5%
(1/198)
0.0%
(0/78)
>.99
3.1%
(3/98)
0.0%
(0/51)
Bowel
5
0.5%
(1/198)
1.3%
(1/78)
.49
0.0%
(0/98)
0.0%
(0/51)
Wound
6
2.0%
(4/198)
5.1%
(4/78)
.23
3.1%
(3/98)
2.0%
(1/51)
Neurologic
7
1.0%
(2/198)
0.0%
(0/78)
>.99
1.0%
(1/98)
3.9%
(2/51)
Vascular
8
3.0%
(6/198)
3.8%
(3/78)
.72
8.2%
(8/98)
5.9%
(3/51)
Freedom from Morbidity
(0-365 days)
76%
(151/200)
49%
(39/80)
<.001
55%
(55/100)
62%
(32/52)
Cardiovascular
2
5.0%
(10/200)
14%
(11/80)
.02
19%
(19/100)
3.8%
(2/52)
Pulmonary
3
1.5%
(3/200)
16%
(13/80)
<.001
6.0%
(6/100)
0.0%
(0/52)
Renal
4, 9,10
2.5%
(5/200)
10%
(8/80)
.01
9.0%
(9/100)
5.8%
(3/52)
Bowel
5
1.5%
(3/200)
3.8%
(3/80)
.36
1.0%
(1/100)
1.9%
(1/52)
Wound
6
5.5%
(11/200)
13%
(10/80)
.08
5.0%
(5/100)
5.8%
(3/52)
Neurologic
7
1.0%
(2/200)
2.5%
(2/80)
.32
1.0%
(1/100)
3.8%
(2/52)
Vascular
8,11
12%
(24/200)
33%
(26/80)
<.001
25%
(25/100)
23%
(12/52)
1
From the morbidity index.
2
Cardiovascular included: Q-wave and non-Q-wave myocardial infarctions, congestive heart failure, arrhythmias requiring new medication or treatment, cardiac ischemia requiring
intervention, inotropic support, medically intractable hypertension.
3
Pulmonary included: reintubation or ventilation >24 hours, pneumonia requiring antibiotics, supplemental oxygen at discharge.
4
Renal included: dialysis in patients with normal preoperative renal function, creatinine rise >30% from baseline on two or more follow-up tests.
5
Bowel included: bowel obstruction, bowel ischemia, aorto-enteric fistula, paralytic ileus >4 days.
6
Wound included: infection requiring antibiotic treatment, hernia, lymph fistula, dehiscence, necrosis requiring debridement.
7
Neurological included: stroke, TIA, spinal cord ischemia/paralysis.
8
Vascular included: limb thrombosis, distal embolization resulting in tissue loss or requiring intervention, transfusion postprocedure (resulting from pseudoaneurysm, vascular injury,
aneurysm leak or other procedure-related causes), pseudoaneurysm, vascular injury (such as inadvertent occlusion, dissection or other procedure related causes), aneurysm leak or
rupture, increase in aneurysm size by more than 0.5 cm relative to the smallest of any prior measurement.
9
Investigators reported one additional high risk patient to have occlusion of an accessory renal artery and one additional high risk patient to have chronic renal insufficiency as “other”
adverse events.
10
Investigators reported one additional roll-in patient to have renal insufficiency and one additional surgical patient to have renal insufficiency as “other” adverse events.
11
Investigators reported one additional roll-in patient to have experienced intraoperative aortic plaque rupture resulting in renal artery occlusion as an “other” adverse event.
