Antiplatelet Strategy for Peripheral Arterial Interventions for Revascularization of Lower Extremities

NCT ID: NCT02217501

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2020-01-30

Brief 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.

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.

Conditions

Peripheral Arterial Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Clopidogrel

Intervention Type: DRUG

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

Acetylsalicylic acid (ASA)

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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

Acetylsalicylic acid (ASA)

Intervention Type: DRUG

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

Interventions

Clopidogrel

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

Intervention Type: DRUG

Acetylsalicylic acid (ASA)

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

Intervention Type: DRUG

Other Intervention Names

Plavix; Aspirin

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Subhash Banerjee

PROFESSOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Subhash Banerjee, MD

Role: STUDY_CHAIR

University of Texas Southwestern Medical Center

Subhash Banerjee, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

Denver VA Medical Center

Denver, Colorado, United States

Midwest Cardiovascular Research Foundation

Davenport, Iowa, United States

VA North Texas Health Care System

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23915884 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21256469 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14709362 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16449620 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16990459 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22981558 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16549646 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

122013-065

Identifier Type: -

Identifier Source: org_study_id

NCT02317822

Identifier Type: -

Identifier Source: nct_alias