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March 2010
COMPLETE SE and Other SFA Trials
A look at the ongoing trials of self-expanding stents in the superficial femoral artery.
Endovascular treatment of peripheral artery disease (PAD) involving the superficial femoral artery (SFA) has evolved with increasing physician experience and improving technologies. Balloon angioplasty alone has excellent initial technical success rates of more than 95%, with a low risk of complications.1 However, restenosis and clinical failure can be high, with restenosis rates in treated segments ranging from 40% to 60%.1-3 With long-segment disease, calcification, total occlusions, and poor runoff, results after balloon angioplasty are suboptimal. Stenting has been promulgated as a treatment option, but stents placed in the SFA are subject to complex and varied mechanical stresses, and stent fractures can occur. Concerns about stent fracture and restenosis in the SFA have made the use of self-expanding stents in the SFA controversial. Despite these difficulties, there has been considerable advancement in the development of stents for the SFA.
Schillinger et al performed a randomized controlled trial comparing the use of self-expanding stents versus balloon angioplasty in 104 patients with severe claudication or critical limb ischemia with disease of the SFA.4 In this study, these investigators from Austria used nitinol selfexpanding Dynalink or Absolute stents from Abbott Vascular (Santa Clara, CA). The investigators showed by duplex ultrasound that stenting was associated with significantly lower rates of restenosis at 12 months (37% vs 63%, P = .01). This was associated with significantly improved walking distance as well.On the other hand, the FAST trial compared the use of the Luminexx nitinol self-expanding stent (Bard Peripheral Vascular, Tempe, AZ) to balloon angioplasty for shorter SFA lesions and did not demonstrate any reduction in restenosis with stenting (31.7% vs 38.6%, P = .38).5 As such, there remains considerable debate regarding the long-term benefit of routine use of stents in the SFA.
Currently in the United States, the Food and Drug Administration has approved only three self-expanding stents for use in the SFA. These are the IntraCoil (ev3 Inc., Plymouth, MN), the Viabahn (W. L. Gore & Associates, Flagstaff, AZ), and the LifeStent (Bard Peripheral Vascular). Of these, only the Viabahn and the LifeStent are commercially available.
Trials to evaluate the use of newer self-expanding stents in the SFA are currently underway in the United States; some of these trials are already completed with preliminary results. These include the Zilver PTX trial (Zilver PTX peripheral drug-eluting self-expanding stent vs Zilver bare-metal stent, Cook Medical, Bloomington, IN)6 and the RESILIENT trial (LifeStent, Bard Peripheral Vascular).7 Other stent trials are ongoing, and they are expected to further improve our understanding of the optimal endovascular treatment of SFA disease. At the same time, the outcomes of these studies will provide the basis for the regulatory approval of the respective stents. These studies include the COMPLETE SE (Medtronic Inc., Minneapolis, MN), STROLL, (SMART stent, Cordis Corporation, Bridgewater, NJ), DURABILITY II (Protégé EverFlex stent, ev3 Inc.), and SUPERB (Supera stent, IDev Technologies, Inc., Houston, TX) trials.
For the current US SFA stents trials, the study population includes patients with moderate-to-severe claudication and rest pain (Rutherford category 2–4). The study designs are prospective, nonrandomized, single-arm registries designed to determine efficacy (primary patency) and safety (major adverse events [MAEs]). Many of the inclusion/exclusion criteria and protocol features are similar among studies. In most of these studies, lesion length is usually limited to no more than 140 mm in order to allow for use of a single 150-mm stent. In this brief review, we will highlight the COMPLETE SE SFA trial as a typical study of self-expanding stents in the SFA and comment on the other ongoing trials in the United States.
COMPLETE SE SFA STUDY
The use of the Medtronic Complete self-expanding
(SE) stent (Figure 1) in the SFA is currently under investigation
in the COMPLETE SE SFA study. This is a prospective,
multicenter, single-arm study, the aim of which is to
evaluate the safety and efficacy of the Complete SE SFA
stent system in the treatment of de novo and/or
restenotic lesions or occlusions in the SFA and/or proximal
popliteal artery in subjects with symptomatic PAD.
The study is currently enrolling patients, and enrollment
is expected to be complete by June 2010.
Design
The study will include up to 30 sites in the United States
and Europe, with an estimated target enrollment of 196
patients. Patients may be included if they have symptomatic
PAD (Rutherford class 2–4) with a lesion ≥ 50%, a
target vessel reference diameter ≥ 4 mm and ≤ 7 mm, a
total lesion length ≥ 40 mm and ≤ 140 mm, and adequate
distal runoff to the foot (at least 1 patent runoff
vessel). Lesions must be located above the knee and be
amenable to percutaneous angioplasty and stenting. The
COMPLETE SE SFA study will have core laboratory evaluation.
Angiograms will be evaluated by an independent
angiographic core lab (Brigham and Women's
Angiographic Core Lab, Boston, MA), and duplex ultrasound
and x-rays will be evaluated by another independent
core lab (VasCore at Massachusetts General Hospital,
Boston, MA).
Primary Endpoints
Analysis of the data will be based on intention-to-treat.
The primary efficacy endpoint is defined as the primary
patency rate at 12 months. Primary patency, in turn, is
defined as uninterrupted patency with no procedures performed
on or at the margins of the treated segment, with
no restenosis ≥ 50% as documented by peak systolic velocity ratio ≥ 2 as assessed by duplex ultrasound. The primary
safety endpoint is defined as the MAE rate at 12 months.
MAEs are defined as device and/or procedure-related
death (or any death occurring after the procedure through
day 30), target limb loss, and clinically driven target lesion
or target vessel revascularization. See Secondary Endpoints
sidebar for a list of the secondary endpoints.
Study subjects must meet study inclusion and exclusion criteria, of which the key ones are listed in the Inclusion/Exclusion Criteria sidebar.
OTHER TRIALS
SUPERB
The SUPERB trial (Comparison of the Supera
Peripheral System to a Performance Goal Derived from
Balloon Angioplasty Clinical Trials in the SFA) is a
prospective, single-arm trial of 258 subjects at up to 40
sites in the United States. It is a nonrandomized, openlabel,
safety and efficacy study that is currently
enrolling. The main objective of this study is to demonstrate
the safety and effectiveness of the IDev Supera
nitinol stent system in treating subjects with obstructive
SFA disease. The primary endpoint will be the primary
patency of the SFA evaluated at 12 months. This
outcome will be compared to a performance goal based
on clinical trials of percutaneous transluminal angioplasty
alone.
DURABILITY II
DURABILITY II is a multicenter, nonrandomized, openlabel,
safety and efficacy study that examines the use of the Protégé Everflex nitinol stent in the endovascular
treatment of symptomatic SFA or proximal popliteal
artery disease. The study design is similar to the
COMPLETE SE trial and is currently recruiting. However,
an additional exclusion criterion is the presence of
symptomatic contralateral disease. The primary efficacy
outcome is primary patency at 1 year. The primary safety
outcome is MAE at 30 days. For more on this trial,
see page 58.
STROLL
The STROLL trial is a multicenter, nonrandomized, single-
arm, prospective trial evaluating the safety and effectiveness
of the SMART nitinol stent in approximately
250 patients with obstructive SFA disease. The primary
efficacy outcome is primary patency at 12 months,
defined as no significant reduction of flow detectable by
duplex ultrasound through the index lesion. The primary
safety outcome is 30-day freedom from all causes
of death, index limb amputation, and target lesion revascularization.
It is currently enrolling subjects. For more
on STROLL, see page 63.
VIPER
The Viabahn endoprosthesis is a self-expanding covered
stent and is already approved by the Food and Drug
Administration for use. The VIPER trial is a nonrandomized,
open-label, single-group, postmarketing study of the
updated Gore Viabahn endoprosthesis. The most recent
iteration of the device comes heparin-bonded and has a
new proximal modification with a lower-profile streamlined
delivery system. The primary outcome is primary
patency at 12 months, defined as no evidence of restenosis
or occlusion within the originally treated lesion based
on color-coded duplex sonography. See page 66 for a
closer look at the VIPER trial.
COMPLETE SE CASE STUDIES
Case 1
A 63-year-old woman with diabetes and hyperlipidemia
presented with severe claudication of her left leg.
Noninvasive studies showed an ankle-brachial index (ABI)
of 0.53, and computed tomographic angiography showed
occlusion in her left SFA, which was confirmed on angiography.
This was successfully treated with balloon angioplasty
and stenting as part of the COMPLETE SE study
(Figure 2).
Case 2
A 54-year-old man with hypertension, hyperlipidemia,
diabetes mellitus, and tobacco use presented with right
lower extremity lifestyle-limiting claudication. His physical examination showed a strong femoral pulse but absent
right popliteal, dorsalis pedis, and posterior tibial pulses.
The resting right ABI was 0.9, and with exercise, this
decreased to 0.3. Computed tomographic angiography
showed focal severe stenosis of the right mid SFA. He then
underwent diagnostic angiography, which showed severe
stenosis of the right SFA. This was successfully treated with
balloon angioplasty and stenting with a Complete SE stent
as shown in Figure 3.
CONCLUSION
There are conflicting data regarding the benefits of
femoropopliteal stenting. Despite the large amount of
SFA stenting that has been performed in recent years,
there are currently three stents that are FDA approved
for use in the SFA. Of these, only the LifeStent and the
Viabahn are commercially available. Studies such as the
COMPLETE SE, SUPERB, Durability II, and STROLL trials
are currently in progress to examine the use of other selfexpanding
stent platforms for use in the SFA for patients
with intermittent claudication and rest pain. These trials
will provide additional data on the safety and efficacy of
these stents in the SFA and will form the basis for regulatory
approval for additional devices.
Khung Keong Yeo, MD, is an interventional fellow at the UC Davis Vascular Center in Sacramento, California. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Yeo may be reached at (916) 734-2028; yeo_kk@yahoo.com.
John R. Laird Jr, MD, is Medical Director of the UC Davis Vascular Center in Sacramento, California. He is the national principal investigator for the COMPLETE SE study and has disclosed that he serves as a consultant and advisory board member for Medtronic. Dr. Laird may be reached at (916) 734-2028; john.laird@ucdmc.ucdavis.edu.
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