Personalizing Thromboprophylaxis for Patients With Peripheral Artery Disease

Purpose

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

Conditions

  • Peripheral Arterial Disease (PAD)
  • Amputation
  • Thrombosis
  • Thrombosis (Stent Thrombosis)
  • Platelet Aggregation Inhibitors
  • Thromboelastography (TEG)
  • PRU(Platelet Reactivity Unit)

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Participants are randomized postoperatively in a 1:1 ratio into one of two groups: the TARGET protocol (interventional arm) or the standard of care (control arm). Randomization uses random block sizes of 2 or 4, stratified by sex and site. Both groups are followed in parallel for 12 months post-revascularization.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Anahita Dua, MBCHB, MBA, MSC
+12625658247
adua1@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Anahita Dua, MBCHB, MBA, MSC
262-565-8247
adua1@mgh.harvard.edu

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.