Personalizing Thromboprophylaxis for Patients With Peripheral Artery Disease

May 21, 2026 updated by: Anahita Dua, MBCHB, MBA, MSC, Massachusetts General Hospital

Personalizing Post Surgical Thromboprophylaxis for Patients With Peripheral Artery Disease

The goal of this clinical trial is to determine whether a personalised blood clot prevention plan is more effective than standard treatment in adults with peripheral artery disease (PAD) who have undergone a procedure to restore blood flow to their legs.

The main questions it aims to answer are:

  • Does the personalized plan lower the rate of blood clots in the treated leg one year after the procedure?
  • Does the personalized plan lower rates of amputation, repeat procedures, bleeding, and death compared to standard treatment?

Researchers will compare the personalized TARGET plan which uses a blood test to tailor each person's blood clot prevention medication to the standard treatment to see if the personalized approach works better.

Participants will:

  • Be randomly assigned to either the personalized TARGET plan or standard treatment after their procedure
  • Have blood tests at 1 week and at 1, 3, 6, 9, and 12 months after their procedure
  • Have medications adjusted based on blood test results if assigned to the TARGET group

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

SCIENTIFIC RATIONALE Graft and stent thrombosis occurs in approximately 17% of PAD patients within 6 months of lower extremity revascularization and is the leading driver of amputation and death in this population. Current standard-of-care (SOC) thromboprophylaxis applies a uniform antiplatelet regimen despite well-documented inter-patient variability in platelet reactivity and drug response - up to 60-65% of PAD patients demonstrate resistance to aspirin or clopidogrel. The absence of personalized, objective thromboprophylaxis strategies represents a critical gap in PAD management.

TECHNOLOGY: THROMBOELASTOGRAPHY WITH PLATELET MAPPING (TEG-PM)

TEG-PM is a whole-blood, point-of-care assay providing real-time assessment of a patient's complete coagulation profile. TEG characterizes clot initiation (R time), kinetics (K time, α angle), maximum clot strength (mA), and fibrinolysis (Lysis 30), enabling discrimination between hypo- and hypercoagulable states. Platelet Mapping quantifies platelet inhibition via arachidonic acid (AA) and adenosine diphosphate (ADP) agonist assays, yielding a platelet inhibition percentage that reflects each patient's real-time pharmacodynamic response to antiplatelet therapy. All samples are analyzed on a TEG 6s (Haemonetics®) Hemostasis Analyzer within validated processing windows using citrated and sodium heparin tubes.

PRELIMINARY DATA A prospective observational study of 162 PAD patients identified platelet inhibition as the sole independent predictor of post-revascularization thrombosis. A threshold of 29% identified high thrombotic risk (87% sensitivity, 71% specificity; AUC 0.756), while an upper threshold of 86% identified elevated bleeding risk (71% sensitivity, 87% specificity; AUC 0.84), defining a therapeutic window of 29-86%. A separate analysis of 521 TEG-PM samples from 143 PAD patients confirmed extensive inter-patient variability in platelet inhibition response, supporting the case against uniform treatment strategies.

Pilot implementation in 34 patients produced a thrombosis rate of 3.8% vs. 20% under SOC (p<0.05) with no increase in bleeding. A subsequent prospective comparison of 70 protocol-guided patients against 267 SOC patients demonstrated thrombosis rates of 4.3% vs. 20.6%, with fewer bleeding events in the protocol-guided arm.

THE TARGET PROTOCOL The Thromboprophylaxis for Arterial Revascularization to Guide Elderly Therapy (TARGET) protocol integrates serial TEG-PM assessments into clinical decision-making to maintain platelet inhibition within the 29-86% therapeutic window throughout 12 months. TEG-PM is first performed at 7 days postoperatively. If platelet inhibition falls outside the therapeutic range, the antiplatelet regimen is adjusted per a prespecified escalation/de-escalation algorithm, with repeat testing 7 days after each change. Once the target range is achieved, monitoring continues at 1, 3, 6, 9, and 12 months with adjustments made as needed. Patients refractory to stepwise adjustments are referred to hematology once for further evaluation and remain enrolled on their last recommended regimen. All patients who receive clopidogrel for at least 7 days undergo VerifyNow P2Y12 resistance testing at a single timepoint to inform agent selection. Control arm patients receive SOC therapy throughout; TEG-PM is collected for data purposes only with no medication adjustments made.

COAGULATION TESTING SCHEDULE TEG-PM samples are collected at: preoperative baseline, 1 week (7-20 days post-op), 1 month (27-47 days), 3 months (85-105 days), 6 months (180-210 days), 9 months (270-295 days), and 12 months (365-390 days). Unscheduled samples may be collected at the PI's discretion in response to clinical events such as thrombosis, bleeding, or inconclusive results.

Study Type

Interventional

Enrollment (Estimated)

484

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Contact:
      • Salem, Massachusetts, United States, 01970
        • Recruiting
        • Salem Hospital (Mass General Brigham)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a named arterial extremity injury or named vessel revascularization for atherosclerosis requiring open and/or closed revascularization.
  • Patients at the age of 18 or older

Exclusion Criteria:

  • Patients who are younger than 18 years old
  • Known pregnancy (females of childbearing potential will have a pregnancy test prior to surgery as per standard of care)
  • Prisoners, defined as those who have been directly admitted from a correctional facility.
  • No atherosclerosis
  • Subject has active stomach ulcers
  • Subject has severe hepatic impairment
  • Subject has a recent history of intracranial hemorrhage. If the patient has a history of cerebral hemorrhage with no new central nervous system disease of >1 year, the study team will consult with the

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TARGET
Participants receive postoperative antiplatelet therapy consistent with standard of care, with regimen adjustments guided by serial TEG-PM (Thromboelastography with Platelet Mapping) assessments. The goal is to maintain platelet inhibition within a therapeutic window of 29-86%. If platelet inhibition falls outside this range at any timepoint, the antiplatelet regimen is escalated or de-escalated per a prespecified algorithm. TEG-PM testing occurs at 1 week, 1, 3, 6, 9, and 12 months postoperatively, with repeat testing 7 days after any medication change.
Drug: Aspirin
Aspirin is an oral antiplatelet agent that inhibits cyclooxygenase-mediated thromboxane A2 production, reducing platelet aggregation. It serves as the foundational antiplatelet agent in both study arms following lower extremity endovascular revascularization.
Other Names:
  • Acetylsalicylic Acid; ASA
Drug: Clopidogrel
Clopidogrel is an oral P2Y12 platelet inhibitor used as part of postoperative antiplatelet therapy following lower extremity endovascular revascularization. In the SOC arm, it is administered as part of a fixed dual antiplatelet regimen. In the TARGET arm, it serves as an initial antiplatelet agent, with continuation or substitution determined by TEG-PM platelet inhibition results and VerifyNow P2Y12 resistance testing. If clopidogrel resistance is identified or platelet inhibition remains below the 29% threshold, clopidogrel may be replaced with ticagrelor per the study algorithm.
Other Names:
  • Plavix
Drug: Ticagrelor
Ticagrelor is an oral, reversible P2Y12 platelet inhibitor. Unlike clopidogrel, ticagrelor demonstrates minimal resistance and more consistent platelet inhibition, making it a preferred escalation agent.
Other Names:
  • Brilinta
Drug: Rivaroxaban
Rivaroxaban is an oral factor Xa inhibitor used in both study arms. In the SOC arm, low-dose rivaroxaban combined with aspirin represents one of two standard postoperative regimens, administered per surgeon preference. In the TARGET arm, rivaroxaban may be initiated or substituted based on TEG-PM platelet inhibition results and clopidogrel resistance testing findings. Full-dose rivaroxaban is reserved for patients who remain persistently hypercoagulable despite stepwise antiplatelet escalation, prior to hematology referral.
Other Names:
  • Xarelto
Device: Thromboelastography with Platelet Mapping
Whole-blood, viscoelastic point-of-care assay used to assess real-time coagulation status and platelet function.
Other Names:
  • TEG-PM
  • TEG 6s
  • Haemonetics TEG 6s Hemostasis Analyzer
Active Comparator: Standard of Care (SOC)
Participants receive standard postoperative antiplatelet therapy per the treating surgeon's preference (dual antiplatelet therapy or aspirin combined with low-dose rivaroxaban) for the 12-month follow-up period. TEG-PM testing is performed at all scheduled timepoints for data collection purposes only; no medication adjustments are made based on results.
Drug: Aspirin
Aspirin is an oral antiplatelet agent that inhibits cyclooxygenase-mediated thromboxane A2 production, reducing platelet aggregation. It serves as the foundational antiplatelet agent in both study arms following lower extremity endovascular revascularization.
Other Names:
  • Acetylsalicylic Acid; ASA
Drug: Clopidogrel
Clopidogrel is an oral P2Y12 platelet inhibitor used as part of postoperative antiplatelet therapy following lower extremity endovascular revascularization. In the SOC arm, it is administered as part of a fixed dual antiplatelet regimen. In the TARGET arm, it serves as an initial antiplatelet agent, with continuation or substitution determined by TEG-PM platelet inhibition results and VerifyNow P2Y12 resistance testing. If clopidogrel resistance is identified or platelet inhibition remains below the 29% threshold, clopidogrel may be replaced with ticagrelor per the study algorithm.
Other Names:
  • Plavix
Drug: Ticagrelor
Ticagrelor is an oral, reversible P2Y12 platelet inhibitor. Unlike clopidogrel, ticagrelor demonstrates minimal resistance and more consistent platelet inhibition, making it a preferred escalation agent.
Other Names:
  • Brilinta
Drug: Rivaroxaban
Rivaroxaban is an oral factor Xa inhibitor used in both study arms. In the SOC arm, low-dose rivaroxaban combined with aspirin represents one of two standard postoperative regimens, administered per surgeon preference. In the TARGET arm, rivaroxaban may be initiated or substituted based on TEG-PM platelet inhibition results and clopidogrel resistance testing findings. Full-dose rivaroxaban is reserved for patients who remain persistently hypercoagulable despite stepwise antiplatelet escalation, prior to hematology referral.
Other Names:
  • Xarelto
Device: Thromboelastography with Platelet Mapping
Whole-blood, viscoelastic point-of-care assay used to assess real-time coagulation status and platelet function.
Other Names:
  • TEG-PM
  • TEG 6s
  • Haemonetics TEG 6s Hemostasis Analyzer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Arterial Thrombosis in the Treated Limb
Time Frame: 12 months post-revascularization
Proportion of participants experiencing graft or stent thrombosis in the revascularized limb, compared between the TARGET and SOC arms. Thrombosis will be assessed via vascular studies including ankle-brachial index, arterial duplex, and toe pressure at scheduled follow-up visits.
12 months post-revascularization

Secondary Outcome Measures

Outcome Measure
Time Frame
Amputation-Free Survival (AFS)
Time Frame: 12 months post-revascularization
12 months post-revascularization
All-Cause Mortality
Time Frame: 12 months post-revascularization
12 months post-revascularization
Reintervention Rate
Time Frame: 12 months post-revascularization
12 months post-revascularization
Incidence of Bleeding Events
Time Frame: 12 months post-revascularization
12 months post-revascularization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Inhibition Level
Time Frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization
Serial TEG-PM derived platelet inhibition percentages tracked over time to assess maintenance within the therapeutic window of 29-86% in the TARGET arm.
1 week, 1, 3, 6, 9, and 12 months post-revascularization
Rutherford Score
Time Frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization

The Rutherford Classification System is a standardized seven-category scale (Grade 0-6) used to classify the severity of peripheral artery disease based on clinical symptoms and hemodynamic measurements.

Category 0 indicates no symptoms with normal hemodynamic findings; Category 1 indicates mild claudication; Category 2 indicates moderate claudication; Category 3 indicates severe claudication; Category 4 indicates ischemic rest pain; Category 5 indicates minor tissue loss; and Category 6 indicates major tissue loss or gangrene.

Higher scores indicate worse limb ischemia and poorer functional status.

The score is assessed by the treating physician at each scheduled follow-up visit.
1 week, 1, 3, 6, 9, and 12 months post-revascularization
Clopidogrel Resistance
Time Frame: Once during follow-up, through study completion, an average of 12 months post-revascularization
Assessed via VerifyNow P2Y12 assay in all patients who receive clopidogrel for at least 7 days during the study period.
Once during follow-up, through study completion, an average of 12 months post-revascularization
Wound Status
Time Frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization
Wound status at the revascularization site is assessed at each scheduled follow-up visit by clinical examination. Clinicians document the presence or absence of a wound and, if present, categorize its status as one of four categories: stable, better, worse, or new wound. Changes in wound status between visits are tracked over time and recorded in conjunction with overall limb status assessment including thrombosis, amputation, and reintervention events.
1 week, 1, 3, 6, 9, and 12 months post-revascularization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 29, 2025

Primary Completion (Estimated)

April 29, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

May 13, 2026

First Submitted That Met QC Criteria

May 21, 2026

First Posted (Actual)

May 29, 2026

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 21, 2026

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024P002975

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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