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CompletedNCT02217501ASPIREUpdated Feb 21, 2021Results posted

Antiplatelet Strategy for Peripheral Arterial Interventions for Revascularization of Lower Extremities

A Phase 3 interventional study of Clopidogrel and Acetylsalicylic acid (ASA) in Peripheral Arterial Disease, sponsored by University of Texas Southwestern Medical Center. Completed at 4 sites in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2021-02-21.

Sponsored by University of Texas Southwestern Medical Center · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
159
Allocation
Randomized
Ages
18 Years to 90 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate whether clopidogrel 75 mg daily on a background of aspirin 75-100 mg/d for clinically indicated duration or for an additional 12 months will lead to an increased rate of primary patency, limb salvage, non-fatal myocardial infarction (MI), ischemic stroke, and survival, in patients receiving endovascular treatment of PAD at end of study treatment.

Read the detailed description

Peripheral arterial disease (PAD) is extremely prevalent worldwide and affects over 206 million people. Over 36 million patients with PAD are estimated to be present in the United States. Percutaneous revascularization therapies have evolved dramatically, yet the long-term success of these therapies remains modest and the morbidity and mortality associated with PAD remains high, with up to 30% mortality risk at 5 years. Nearly, 3.2 million endovascular procedures are performed annually. Though, this exceeds interventional procedures performed for coronary artery disease (CAD), the current PAD guidelines are silent regarding the need and optimal duration of antiplatelet therapy (APT) for patients following an endovascular procedure for claudication or critical limb ischemia (CLI). The lack of data and clinical studies is by far the greatest impediment to the formulation of such guideline recommendations critically needed by providers and patients alike, especially given the current limited durability of lower extremity endovascular procedures.

The objective of this trial is to evaluate whether clopidogrel 75 mg QD on a background of ASA 75-100 mg/d for clinically indicated duration or for an additional 12 months will lead to an increased rate of primary patency, limb salvage, non-fatal myocardial infarction (MI), ischemic stroke, and survival, in patients receiving endovascular treatment of PAD at end of study treatment.

The investigators hypothesize that dual antiplatelet therapy (DAPT) with ASA and clopidogrel administered for an additional 12 months following iliac, femoropopliteal or below the knee endovascular intervention will improve primary patency, limb salvage, freedom from ischemic stroke and survival, in patients with symptomatic PAD.

Clinical endpoints will be analyzed in all subjects who are enrolled, regardless of whether the trial treatment administered successfully completed for the desired duration. A subject will be considered enrolled in the trial when he/she is randomized to one of the treatment arms of the study. All endpoints are subject-based unless otherwise specified.

The primary endpoint is subject-based of the longer of a 12-month or end of study treatment endpoint of the first occurrence of index limb arterial occlusion, surgical intervention, endovascular intervention, amputation of the affected limb (primary patency and limb salvage), MI, ischemic stroke or death (survival).

The secondary endpoints are subject-based on the longer of a 12 month or end of study treatment endpoints that include: (a) the first occurrence of any individual component of the primary endpoint, (b) the first occurrence of the following during follow-up: cardiovascular death, or MI, or ischemic stroke, or any amputation above the ankle and (c) severe bleeding defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification.

The tertiary endpoint is based on the longer of a 12-month or end of study moderate bleeding according to the GUSTO classification.

02

Conditions studied

  • Peripheral Arterial Disease

Keywords

  • peripheral arterial disease, antiplatelet therapy
03

In context

Peripheral Arterial Disease

1,542 studies on the registry are indexed under Peripheral Arterial Disease; 282 are open to participants now.

This study's enrollment of 159 is above the median of 74 across 1,066 interventional studies indexed under Peripheral Arterial Disease.

Browse Peripheral Arterial Disease studies →

Lead sponsor

University of Texas Southwestern Medical Center is the lead sponsor of 990 studies on the registry; 201 are open to participants now.

Of its 135 completed or terminated interventional studies of FDA-regulated products, 100 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

General:

  • Signed informed consent
  • At least 18 years old
  • Documented symptomatic iliac, femoropopliteal (FP) or below-the knee artery (BTK) atherosclerotic disease (Rutherford/Becker category 2, 3 or ≥4)
  • Undergone clinically indicated uncomplicated endovascular intervention to one or more locations of the iliac, femoropopliteal below-the knee arteries
  • Estimated survival ≥1 year in the judgment of the primary operator
  • Pre-index procedure use of ASA, clopidogrel or both at any dose

Angiographic:

  • De novo or restenotic lesions in the common and/or external iliac artery, superficial femoral artery (SFA), popliteal artery, tibio-peroneal (TP) trunk, anterior tibial (AT) artery, peroneal artery (PA) or posterior tibial (PT) artery (applies to all target lesions if multiple)
  • Subjects with multiple planned procedures can be enrolled after the completion of the last planned procedure.

Exclusion criteria

Exclusion Criteria:

General:

  • Complicated qualifying procedure (perforation, flow limiting dissection, distal embolization requiring re-intervention, need for repeat endovascular, surgical revascularization, amputation or blood transfusion prior to hospital discharge following an index procedure
  • Extended hospital stay >7 days following the index procedure
  • Allergy to aspirin or clopidogrel
  • Life expectancy less than 12 months due to other medical co-morbid condition(s) that could limit the subject's ability to participate in the trial, limit the subject's compliance with the follow-up requirements, or impact the scientific integrity of the trial
  • Known hypersensitivity or contraindication to contrast dye that, in the opinion of the investigator, cannot be adequately pre-medicated.
  • Intolerance to antiplatelet, anticoagulant, or thrombolytic medications
  • Platelet count \<90,000 mm3 or >600,000 mm3
  • Serum creatinine >2.5 mg/dL
  • Dialysis-dependent end stage renal disease
  • Pregnancy
  • Current participation in another drug or device trial that requires interruption of dual-antiplatelet therapy with aspirin or clopidogrel for the duration of the study
  • Planned surgeries, endovascular or other non-vascular or cardiac procedures
  • Concurrent warfarin or other chronic oral anticoagulant therapy
  • Contraindication(s) to the use of AT (history of intra-cerebral bleed, presence of intra-cerebral mass, recent or \<6 weeks gastrointestinal bleed, blood transfusion within the last 6 weeks, any trauma requiring surgery or blood transfusion within the last 4 weeks or any surgical procedure within the last 4 weeks.

Angiographic:

  • Endovascular intervention to iliac, femoropopliteal or BTK artery bypass graft
  • Persistent, intraluminal thrombus of the proposed target lesion at the completion of the index procedure
  • Perforated vessel as evidenced by extravasation of contrast media
  • Vascular graft, aneurysm or postsurgical stenosis of the target vessel
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Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
159 participants (actual)

Study arms

  • Experimental
    DAPT - clinically indicated duration+12m

    Clopidogrel 75 mg daily and Acetylsalicylic acid (ASA) 75-100 mg daily for clinically indicated duration plus an additional 12 months

    Drug: Clopidogrel · Drug: Acetylsalicylic acid (ASA)

  • Active comparator
    DAPT - clinically indicated duration

    Clopidogrel 75 mg daily and Acetylsalicylic acid (ASA) 75-100 mg daily for clinically indicated duration with a minimum of 30 days

    Drug: Clopidogrel · Drug: Acetylsalicylic acid (ASA)

Interventions

  • DrugClopidogrel

    Clopidogrel 75 mg once daily for clinically indicated duration or for clinically indication duration + 12 months

    Also known as: Plavix

  • DrugAcetylsalicylic acid (ASA)

    Acetylsalicylic acid (ASA) 75-100 mg once daily for clinically indicated duration or for clinically indication duration + 12 months

    Also known as: Aspirin

06

What researchers measure

Primary outcomes

  1. Number of Participants With First Occurrence of Target Vessel Occlusion, Surgical Revascularization, Endovascular Revascularization, Major Amputation of Target Limb, Ischemic Stroke, MI, or Death

    Occlusion of the target vessel documented by any imaging procedure (eg, Duplex ultrasonography scan including B mode imaging and Doppler ultrasound scan) at any follow-up visit within 12 months or end of study treatment period, whichever is longer.

    Time frame: 12 months from index procedure or end of study treatment, whichever is longer, assessed up to 2 years

Secondary outcomes

  1. Number of Participants With First Occurrence of Bleeding

    Any mild, moderate, severe, or life-threatening bleeding. Severe or Life-threatening: Intracerebral hemorrhage Resulting in substantial hemodynamic compromise requiring treatment Moderate: Requiring blood transfusion but not resulting in hemodynamic compromise Mild: Bleeding that does not meet above criteria Severe bleeding defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification.

    Time frame: 12 months from index procedure or end of study treatment, whichever is longer, assessed up to 2 years

07

Results

Posted Feb 21, 2021
Limitations and caveats
Study was not able to reach the target number of participants needed to achieve target power and statistically reliable results.

Participant flow

Participant flow — Overall Study
MilestoneDAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated Duration
Started7782
Completed7478
Not completed34
Withdrew: Death34

Outcome measures

PrimaryNumber of Participants With First Occurrence of Target Vessel Occlusion, Surgical Revascularization, Endovascular Revascularization, Major Amputation of Target Limb, Ischemic Stroke, MI, or Death

Occlusion of the target vessel documented by any imaging procedure (eg, Duplex ultrasonography scan including B mode imaging and Doppler ultrasound scan) at any follow-up visit within 12 months or end of study treatment period, whichever is longer.

Time frame:
12 months from index procedure or end of study treatment, whichever is longer, assessed up to 2 years
Reported as:
Count of participants · Participants
Number of Participants With First Occurrence of Target Vessel Occlusion, Surgical Revascularization, Endovascular Revascularization, Major Amputation of Target Limb, Ischemic Stroke, MI, or Death
ParticipantsDAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated Duration
Number of Participants With First Occurrence of Target Vessel Occlusion, Surgical Revascularization, Endovascular Revascularization, Major Amputation of Target Limb, Ischemic Stroke, MI, or Death1316
SecondaryNumber of Participants With First Occurrence of Bleeding

Any mild, moderate, severe, or life-threatening bleeding. Severe or Life-threatening: Intracerebral hemorrhage Resulting in substantial hemodynamic compromise requiring treatment Moderate: Requiring blood transfusion but not resulting in hemodynamic compromise Mild: Bleeding that does not meet above criteria Severe bleeding defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification.

Time frame:
12 months from index procedure or end of study treatment, whichever is longer, assessed up to 2 years
Reported as:
Count of participants · Participants
Number of Participants With First Occurrence of Bleeding
ParticipantsDAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated Duration
Number of Participants With First Occurrence of Bleeding54
Statistical analysis
  • DAPT - Clinically Indicated Duration+12m vs DAPT - Clinically Indicated Duration · Cochran-Mantel-Haenszel · p = 0.6595 (Alpha of 0.05)

Adverse events

Collected over Adverse events were collected from the time on informed consent and up to 18 months.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
DAPT - Clinically Indicated Duration+12m3/77 (3.9%)27/77 (35.1%)1/77 (1.3%)
DAPT - Clinically Indicated Duration4/82 (4.9%)37/82 (45.1%)1/82 (1.2%)
Most frequent serious events
Most frequent serious events
EventDAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated Duration
Repeat Endovascular RevascularizationVascular disorders13/7716/82
AmputationSurgical and medical procedures7/7712/82
BleedingBlood and lymphatic system disorders3/772/82
Myocardial InfarctionCardiac disorders1/773/82
Bleeding requiring transfusionSurgical and medical procedures2/772/82
StrokeBlood and lymphatic system disorders1/772/82
Most frequent other events
Most frequent other events
EventDAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated Duration
CT/MR AngiographySurgical and medical procedures1/771/82

Baseline characteristics

Age, Continuous
Age, Continuous(years)DAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated DurationTotal
Mean65.62 ± 8.8265.27 ± 8.9065.44 ± 9.00
Sex: Female, Male
Sex: Female, Male(Participants)DAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated DurationTotal
Female121426
Male6568133
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)DAPT - Clinically Indicated Duration+12mDAPT - Clinically Indicated DurationTotal
Count of participants——0
08

Study locations

4 sites
  • Denver VA Medical Center
    Denver, Colorado 80220, United States
  • Midwest Cardiovascular Research Foundation
    Davenport, Iowa 52803, United States
  • VA North Texas Health Care System
    Dallas, Texas 75216, United States
  • University of Texas Southwestern Medical Center
    Dallas, Texas 75390, United States
09

References and documents

Publications

  • Hirsch AT, Duval S. The global pandemic of peripheral artery disease. Lancet. 2013 Oct 19;382(9901):1312-4. doi: 10.1016/S0140-6736(13)61576-7. Epub 2013 Aug 1. No abstract available. PubMed 23915884 ↗
  • Parikh SV, Saya S, Divanji P, Banerjee S, Selzer F, Abbott JD, Naidu SS, Wilensky RL, Faxon DP, Jacobs AK, Holper EM. Risk of death and myocardial infarction in patients with peripheral arterial disease undergoing percutaneous coronary intervention (from the National Heart, Lung and Blood Institute Dynamic Registry). Am J Cardiol. 2011 Apr 1;107(7):959-64. doi: 10.1016/j.amjcard.2010.11.019. Epub 2011 Jan 20. PubMed 21256469 ↗
  • Diehm C, Schuster A, Allenberg JR, Darius H, Haberl R, Lange S, Pittrow D, von Stritzky B, Tepohl G, Trampisch HJ. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis. 2004 Jan;172(1):95-105. doi: 10.1016/s0021-9150(03)00204-1. PubMed 14709362 ↗
  • Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006 Feb 1;295(5):547-53. doi: 10.1001/jama.295.5.547. PubMed 16449620 ↗
  • Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery/Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines. ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease)--summary of recommendations. J Vasc Interv Radiol. 2006 Sep;17(9):1383-97; quiz 1398. doi: 10.1097/01.RVI.0000240426.53079.46. No abstract available. PubMed 16990459 ↗
  • 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. PubMed 22981558 ↗
  • Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006 Mar 21;113(11):e463-654. doi: 10.1161/CIRCULATIONAHA.106.174526. No abstract available. PubMed 16549646 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 23, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Study results will be posted on clinical.trials.gov and through publications and presentations

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 21, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02217501
Lead sponsor
University of Texas Southwestern Medical Center
Responsible party
Subhash Banerjee (PROFESSOR, University of Texas Southwestern Medical Center) — Principal investigator
First posted
Aug 15, 2014
Start date
Nov 2015
Primary completion
Jan 30, 2020
Completion
Jan 30, 2020
Results posted
Feb 21, 2021
Last update
Feb 21, 2021

Study contacts

Subhash Banerjee, MD
principal investigator · University of Texas Southwestern Medical Center
Subhash Banerjee, MD
study chair · University of Texas Southwestern Medical Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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