Clinical trial NCT03671655: Excellence in Peripheral Arterial Disease Treatment of Superficial Femoral Artery Disease With Drug-eluting Stents
Official title: Excellence in Peripheral Arterial Disease Treatment of Superficial Femoral Artery Disease With Drug-eluting Stents (XL PAD SFA DES)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Peripheral Vascular Diseases
Chronic Total Occlusion of Artery of the Extremities
Keywords: Superficial femoral artery
chronic total occlusion
Lead sponsor: North Texas Veterans Healthcare System
Sponsor class: FED
First posted: 2018-09-14
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase 3, multi-center, randomized controlled, parallel-group study in patients with long Superficial Femoral Artery (SFA) lesions and SFA Chronic Total Occlusion (CTO), undergoing clinically indicated stent-based percutaneous revascularization .Patients will be randomized into Drug eluting stent (DES) arm (intervention) vs. Bare Metal Stent (BMS) arm (control).
Primary purpose: TREATMENT

Brief summary: The superficial femoral artery (SFA) is frequently involved in atherosclerosis and is the most common target of lower extremity endovascular procedures performed in patients with claudication. Endovascular treatment of SFA is challenging, given its exceptional predisposition to atherosclerosis and its exposure to extreme mechanical forces of extension, compression, torsion and flexion. The SFA is located in a fibro-muscular canal, follows a tortuous course and is considered a 'hostile' location for endovascular procedures, especially stents due to the risk of stent fracture. On the other hand, durability of balloon angioplasty in the SFA is dismal (25% patency at 1 year). Therefore, Nitinol (a metal alloy of nickel and titanium) stent implantation is the mainstay of endovascular SFA interventions when balloon angioplasty (PTA) leads to sub-optimal results during a procedure. It is used in over 70% of all cases and in nearly 100% of all femoro-popliteal (FP) CTO (chronic total occlusions) and long (≥60 mm) interventions. Endovascular treatment of SFA is challenging and restenosis is the most common cause for the lack of durability of a SFA peripheral vascular interventional procedure.5 Restenosis rates of SFA bare metal (nitinol) stents or BMS at 1 year exceeds 50% for lesions ≥60 mm in length or CTO. Stent based treatment of the SFA may not offer any additional advantage for short non-CTO (\<60 mm) lesions compared to PTA. In a recent study, primarily comparing drug-eluting stents (DES) to balloon angioplasty in the SFA, 12 month patency rates were 83.1% and 32.8%, respectively for DES and balloon angioplasty arms. However, there are no head-to head studies randomized studies comparing DES and BMS in the SFA. Thus, endovascular SFA intervention in patients with symptomatic PAD is an area of urgent need for high-quality evidence as volume of these procedures continues to rise exponentially in the U.S. and around the world, largely on the basis of insufficient evidence.Thus, the purpose of this study is to conduct a randomized pilot trial comparing DES and BMS for percutaneous revascularization of SFA.

Detailed description: Current practice of SFA revascularization almost always results in use of a Nitinol (a nickel-titanium alloy) BMS. Balloon angioplasty of complex SFA lesions, such as CTO or ≥60 mm lesions is associated with \>50% restenosis at 1-year and Nitinol stents have outperformed stainless-steel stents in the SFA. Debulking strategies are employed selectively and rarely as a stand-alone therapy of SFA CTO. Stent use in long SFA lesions and CTO is fraught with the risk of fracture, mechanical deformation, neo-intimal hyperplasia and thrombosis, each of which is associated with loss of patency. Repeat procedures for in-stent restenosis are technically difficult, carry a higher morbidity compared to the initial procedure and provide less symptom relief. Therefore improving the patency of the initial procedure is in the best interest of the patient and the operator. Though long SFA lesions and CTO constitute ≥50% of all SFA lesions, it is systematically under-represented in the current SFA randomized trials. Stenting has not been shown to be superior to balloon angioplasty for short (30-60 mm) SFA lesions.SFA stenting is associated with lower patency rates and is especially less durable in diabetics, who have a higher prevalence of long lesions and CTO. In one of the largest to date outcome analyses of Nitinol stents in the SFA, 56% of lesions constituted a CTO. Seventy two percent of lesions treated with stents presented with in-stent restenosis compared to 52% of lesions stented for non-CTO lesions (p\<0.001). In a multivariate analysis of stent patency, presence of a long lesion or CTO was an independent adverse predictor (hazard rate or HR=5.075, 95% confidence interval or CI 2.715-9.487). It is important to note that the benefit of stents is greater for longer and more complex lesions, including SFA CTO and long (≥60 mm) lesions.

Study subjects will be recruited from the group of patients who are referred for clinically indicated endovascular treatment of SFA for claudication at the Dallas VA Medical Center and at other participating study sites. The study the investigators propose is significant because: (a) it would affect many veterans, (b) the consequences of early SFA stent failure are grave, (c) treatment of SFA lesions is challenging, and (d) outcomes after treatment of SFA lesions are poor and may be improved with DES. In summary, failure of stent patency after initial revascularization with stenting is common and carries significant morbidity. If restenosis rates of SFA stents can be reduced with DES, it could significantly improve procedural success, durability of treatment, quality of life of patients, reduce the need for repeat revascularization procedures, and potentially reduce healthcare costs.

The proposed study is a phase 3, randomized controlled, parallel-group study in patients with long SFA lesions and SFA CTO, undergoing clinically indicated stent-based percutaneous revascularization.

End points :

The primary study end point is binary restenosis, as assessed by duplex ultrasonography performed at 12 months post-procedure or earlier if clinically indicated. Binary restenosis is defined as ≥2.5 fold increase in PSVR within the stented segment and within 10 mm of its proximal and distal edges to that recorded proximal to the stented segment or by the presence of an occluded stent with no flow. Secondary endpoints included change of resting ankle-brachial index (ABI) and symptoms (Rutherford-Becker stages), at 12 months post-procedure. Patients will be asked to complete a walking impairment questionnaire (score range: 0 to 14,080) pre-intervention, and then at 12 months for the first year post-procedure.19 All analyses will be performed in a blinded fashion at the Veterans Affairs North Texas Clinical Angiographic and Ultrasound Core Laboratory and clinical adjudication and adverse events monitoring will be performed by an independent data oversight and safety monitoring board.

Statistical analysis :

The investigators calculated a priori that 55 vascular segments would be needed in each study arm to have 80% power to detect a reduction in binary restenosis from 40% in the BMS arm to 15% in the DES arm, assuming 10% attrition and an alpha of 0.05. Continuous variables will be summarized as mean ± standard deviation and compared using the t-test or the Wilcoxon rank-sum test, as appropriate. Discrete variables will be presented as frequencies and group percentages compared using the chi-square test or Fisher's Exact Test, as appropriate. Freedom from restenosis will be assessed using Kaplan-Meier curves and log-rank test. For all comparisons a two-sided probability of \<0.05 will be considered statistically significant. All analyses will be performed using SAS 9.1 (SAS Institute Inc., Cary, North Carolina).

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older
2. Referred for clinically indicated lower extremity angiography and peripheral arterial intervention
3. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
4. Absence of allergy to both clopidogrel and aspirin
5. Negative pregnancy test or breast-feeding
6. No coexisting conditions that limit life expectancy to less than 12 months or that could affect a patient's compliance with the protocol as per the site investigator
7. Serum creatinine \<2.5 mg/dL
8. Baseline hemoglobin \>9 g/dl
9. Baseline platelet count \>80,000/L
10. Absence of prior stroke or transient ischemic attack within 3 months
11. ≥30 days from any prior surgical or endovascular procedure

Angiographic enrollment criteria:

1. Undergoing SFA revascularization with the intention for stent implantation
2. De novo SFA lesion ≥60 mm in length by visual estimation
3. Successfully crossed de novo SFA CTO of any length by visual estimation

Exclusion Criteria:

1. SFA lesion involving \<5mm of ostial SFA and/or profunda femoris artery take-off
2. SFA lesion extending below the medial femoral epicondyle
3. \<1 vessel below-the knee (BTK) run-off

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Primary outcomes:
measure: SFA stent patency
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants.
Secondary outcomes:
measure: Crossing time
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: Procedural duration
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: Composite of Major Adverse Events
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: Ankle Brachial Index
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: Rutherford Category
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: Walking Impairment Questionnaire (WIQ)
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
measure: 6 minute Walking Test
timeFrame: 12 months - The study was closed due to lower than anticipated eligible participants
Other outcomes:
Locations:
city: Dallas
country: United States
facility: North Texas Veterans Affairs Health Care System
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: North Texas Veterans Health Care System, Dallas, TX
name: Subhash Banerjee, MD
role: STUDY_CHAIR
References:
citation: Scheinert D, Scheinert S, Sax J, Piorkowski C, Braunlich S, Ulrich M, Biamino G, Schmidt A. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol. 2005 Jan 18;45(2):312-5. doi: 10.1016/j.jacc.2004.11.026.
citation: Rocha-Singh KJ, Jaff MR, Crabtree TR, Bloch DA, Ansel G; VIVA Physicians, Inc. Performance goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease. Catheter Cardiovasc Interv. 2007 May 1;69(6):910-9. doi: 10.1002/ccd.21104.
citation: Krankenberg H, Schluter M, Steinkamp HJ, Burgelin K, Scheinert D, Schulte KL, Minar E, Peeters P, Bosiers M, Tepe G, Reimers B, Mahler F, Tubler T, Zeller T. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST). Circulation. 2007 Jul 17;116(3):285-92. doi: 10.1161/CIRCULATIONAHA.107.689141. Epub 2007 Jun 25.
citation: Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, Zeller T, Roubin GS, Burket MW, Khatib Y, Snyder SA, Ragheb AO, White JK, Machan LS; Zilver PTX Investigators. Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: twelve-month Zilver PTX randomized study results. Circ Cardiovasc Interv. 2011 Oct 1;4(5):495-504. doi: 10.1161/CIRCINTERVENTIONS.111.962324. Epub 2011 Sep 27.
citation: Schillinger M, Sabeti S, Loewe C, Dick P, Amighi J, Mlekusch W, Schlager O, Cejna M, Lammer J, Minar E. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006 May 4;354(18):1879-88. doi: 10.1056/NEJMoa051303.
citation: Banerjee S, Das TS, Abu-Fadel MS, Dippel EJ, Shammas NW, Tran DL, Zankar A, Varghese C, Kelly KC, Weideman RA, Little BB, Reilly RF, Addo T, Brilakis ES. Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents for revascularization of peripheral arterial segments: the COBRA trial. J Am Coll Cardiol. 2012 Oct 9;60(15):1352-9. doi: 10.1016/j.jacc.2012.05.042. Epub 2012 Sep 12.