An interventional study of Aspirin and Clopidogrel in Peripheral Arterial Disease (PAD), Amputation and Thrombosis, sponsored by Massachusetts General Hospital. Recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Massachusetts General Hospital · Not applicable, Interventional, and Treatment
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:
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:
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.
1,377 studies on the registry are indexed under Peripheral Arterial Disease; 275 are open to participants now.
This study's planned enrollment of 484 is above the median of 70 across 927 interventional studies indexed under Peripheral Arterial Disease.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 · Drug: Clopidogrel · Drug: Ticagrelor · Drug: Rivaroxaban · Device: Thromboelastography with Platelet Mapping
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 · Drug: Clopidogrel · Drug: Ticagrelor · Drug: Rivaroxaban · Device: Thromboelastography with Platelet Mapping
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.
Also known as: Acetylsalicylic Acid; ASA
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.
Also known as: Plavix
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.
Also known as: Brilinta
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.
Also known as: Xarelto
Whole-blood, viscoelastic point-of-care assay used to assess real-time coagulation status and platelet function.
Also known as: TEG-PM, TEG 6s, Haemonetics TEG 6s Hemostasis Analyzer
Incidence of Arterial Thrombosis in the Treated Limb
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.
Time frame: 12 months post-revascularization
Amputation-Free Survival (AFS)
Time frame: 12 months post-revascularization
All-Cause Mortality
Time frame: 12 months post-revascularization
Reintervention Rate
Time frame: 12 months post-revascularization
Incidence of Bleeding Events
Time frame: 12 months post-revascularization
Platelet Inhibition Level
Serial TEG-PM derived platelet inhibition percentages tracked over time to assess maintenance within the therapeutic window of 29-86% in the TARGET arm.
Time frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization
Rutherford Score
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.
Time frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization
Clopidogrel Resistance
Assessed via VerifyNow P2Y12 assay in all patients who receive clopidogrel for at least 7 days during the study period.
Time frame: Once during follow-up, through study completion, an average of 12 months post-revascularization
Wound Status
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.
Time frame: 1 week, 1, 3, 6, 9, and 12 months post-revascularization
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Studies of the drugs tested here: Aspirin · Clopidogrel · Ticagrelor · Rivaroxaban
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