Thromboelastography With Platelet Mapping to Guide Antiplatelet Therapy After Lower Extremity Revascularization (TARGET)

Mass General Brigham

Status: Active, not recruiting

Conditions: Platelet Inhibition; Thrombosis; Arterial Occlusive Diseases; Peripheral Arterial Disease(PAD); Thromboelastography (TEG); PRU(Platelet Reactivity Unit); Stent Thrombosis

Treatments: Diagnostic Test: Platelet Reactivity Testing; Drug: Aspirin; Diagnostic Test: Thromboelastography with Platelet Mapping; Drug: Ticagrelor; Drug: Clopidogrel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07597239

2022P002264 (Other Identifier)

R21AG077310 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal of this clinical trial is to learn if a blood clotting test called thromboelastography with platelet mapping (TEG-PM) can guide blood-thinning medication decisions in adults more than 60 years and older with peripheral artery disease (PAD) who have undergone infrainguinal endovascular surgery. The main questions it aims to answer are:

• Does TEG-PM-guided antiplatelet therapy lower the rate of thrombosis or clinically significant stenosis of the treated artery within 12 months compared with a historical standard-of-care cohort?
• How does TEG-PM-guided therapy affect major amputation, amputation-free survival, mortality, and bleeding?

Participants will:

• Have blood samples taken before the procedure and at 1, 3, and 6 months afterward
• Have antiplatelet medications (aspirin, clopidogrel, and/or ticagrelor) escalated or de-escalated based on TEG-PM results through 6 months
• Have one additional blood test to check clopidogrel response if taking clopidogrel
• Be followed for clinical outcomes through 12 months

Full description

Background and Scientific Rationale

Peripheral artery disease (PAD) affects more than 200 million people worldwide and frequently requires lower extremity revascularization, most commonly by endovascular approaches. Despite guideline-directed antiplatelet therapy, thrombotic occlusion or clinically significant restenosis occurs in approximately 20% of patients within 12 months of revascularization and is a leading cause of repeat intervention and amputation. Current thromboprophylaxis strategies apply a uniform regimen that does not account for substantial interpatient variability in platelet response; 60-65% of vascular patients exhibit partial or complete resistance to aspirin or clopidogrel.

Thromboelastography with platelet mapping (TEG-PM) is a point-of-care whole-blood viscoelastic assay that assesses clot initiation, kinetics, strength, and fibrinolysis, as well as pathway-specific platelet function. These include adenosine diphosphate (ADP)-mediated platelet inhibition, which reflects P2Y12 pathway activity and clopidogrel/ticagrelor effect, and arachidonic acid (AA)-mediated platelet inhibition, which reflects cyclooxygenase pathway activity and aspirin effect.

In prior prospective observational work, this group demonstrated that an ADP-mediated platelet inhibition value below 29.2% predicted thrombosis or clinically significant stenosis after lower extremity revascularization with 87% sensitivity and 70% specificity (Majumdar et al., J Am Heart Assoc 2023). Subsequent work identified high ADP-mediated platelet inhibition as associated with bleeding risk (Rodriguez Alvarez et al., J Surg Res 2025). A pilot study implementing TEG-PM-guided therapy was associated with reduced thrombosis or clinically significant stenosis compared with historical institutional rates (Suarez et al., Ann Surg 2024). Based on these findings, the Thromboprophylaxis for Arterial Revascularization to Guide Elderly Therapy (TARGET) protocol was developed.

TARGET Protocol (TEG-PM-Guided Antiplatelet Therapy)

Postoperative antiplatelet therapy is adjusted according to ADP-mediated platelet inhibition on TEG-PM:

Platelet inhibition <30% (hypercoagulable; increased thrombosis/stenosis risk) → escalate antiplatelet therapy.

Platelet inhibition 30-86% (therapeutic range) → continue current regimen. Platelet inhibition >86% (hypocoagulable; increased bleeding risk) → de-escalate antiplatelet therapy.

Escalation follows this stepwise sequence:

1. Aspirin monotherapy (81 mg daily)
2. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (75 mg daily)
3. DAPT with aspirin and ticagrelor (90 mg twice daily) replacing clopidogrel
4. Triple antiplatelet therapy (aspirin, clopidogrel, and ticagrelor) if hypercoagulability persists

De-escalation follows the same sequence in reverse order. Participants whose platelet inhibition values fall outside protocol-defined ranges or remain abnormal despite adjustment are referred to hematology for further evaluation.

TEG-PM Blood Sampling and Analysis:

Two sample types are collected at each visit:

• Citrated blood (sodium citrate Vacutainer tubes): incubated at room temperature for 10 minutes; analyzed using citrated multichannel cartridges to assess coagulation initiation, kinetics, clot strength, and fibrinolysis. Must be processed within 2-4 hours of collection.
• Heparinized blood (sodium heparin Vacutainer tubes): incubated at room temperature for 30 minutes; analyzed using PlateletMapping cartridges to measure ADP-mediated and AA-mediated platelet aggregation and inhibition. - Must be processed within 2 hours of collection.

All samples are analyzed using the TEG 6s Hemostasis Analyzer (Haemonetics Corporation, Boston, MA) per manufacturer specifications. Up to two citrated tubes and one heparinized tube are drawn at each timepoint. In the event of insufficient blood volume, TEG-PM will be prioritized.

Study Phases:

1. Pre-operative Phase:

   Blood sample collected within 48 hours before the planned revascularization procedure. If the procedure is delayed or rescheduled beyond this window, a new sample is collected.

2. Interventional Phase (through 6 months):

TEG-PM samples are collected at 1, 3, and 6 months after the index procedure, and the results guide antiplatelet adjustments per the TARGET protocol.)

Unscheduled visits may occur if the principal investigator deems additional sampling necessary for patient safety, including readmission, clotting event, bleeding event, reintervention, inconclusive results, or medication change after 7 days.

Follow-up phase (6-12 months):

After the 6-month visit, antiplatelet management is transferred to the treating surgeon. Clinical follow-up continues through 12 months, at visits approximately 1, 3, 6, and 12 months after the procedure.

Outcome ascertainment:

Outcomes are determined from clinic visits, hospitalizations, procedural reports, imaging, and medical record review through 12 months. For participants who discontinue study visits, ascertainment continues through medical record review.

Medication Adherence Criteria:

TEG-PM results are used to guide therapy only when participants are confirmed adherent:

• Antiplatelet therapy: most recent dose taken within 7 days of sampling
• Anticoagulant therapy: most recent dose taken within 72 hours of sampling

Clopidogrel Resistance Testing:

Participants taking clopidogrel undergo one-time clopidogrel resistance testing using the VerifyNow P2Y12 assay after at least 7 days of therapy. One citrated blood tube (3cc) is collected at MGH and couriered to Brigham and Women's Hospital hematology laboratory for analysis.

Disease Severity Assessment:

PAD severity is assessed using Rutherford clinical category, index-limb ankle-brachial index, and toe-brachial index. Rutherford category 4 defines ischemic rest pain and categories 5-6 define ischemic tissue loss.

• Walking frequency and distance before pain onset
• Presence of rest pain or nocturnal pain
• Presence of non-healing wounds

Outcomes and Comparator

The main clinical endpoint is a composite of thrombosis or clinically significant stenosis of the treated arterial segment within 12 months. Clinically significant stenosis is defined as duplex PSV >300 cm/s and PSVR ≥3.5, accompanied by recurrent ischemic symptoms, an ABI decrease >0.2 from post-procedure, or repeat target-lesion revascularization. Secondary endpoints include major amputation of the index limb, amputation-free survival, all-cause mortality, ISTH major bleeding, and ISTH clinically relevant non-major bleeding.

Outcomes are compared with a prospectively collected historical observational cohort enrolled at the same institution from December 2020 to December 2022 (IRB protocol 2022P001918). That cohort met the same eligibility criteria and underwent serial TEG-PM testing, but the results were blinded to treating clinicians, and antiplatelet therapy followed standard of care.

A minimum of 107 TARGET participants was required to provide 80% power at two-sided α = 0.05, based on effect sizes from the pilot study.

Enrollment: 144 patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients requiring infrainguinal endovascular revascularization for peripheral atherosclerosis
• Patients of age 60 or older

Exclusion criteria

• Did not undergo an eligible infrainguinal endovascular intervention (e.g., no treatable atherosclerotic lesion, unsuitable anatomy, diagnostic angiography only, or alternative treatment selected)
• Hybrid procedures involving a substantial open infrainguinal revascularization component (femoral cutdown with infrainguinal endovascular treatment is permitted)
• Contraindication to standard antiplatelet therapy
• Pregnancy or breastfeeding
• Inability to undergo serial venous blood sampling
• Inability to provide informed consent
• Non-atherosclerotic pathology identified as primary etiology

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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144 participants in 1 patient group

TARGET (TEG-PM-Guided Antiplatelet Therapy)

Experimental group

Description:

All participants undergo serial TEG-PM before and after infrainguinal endovascular revascularization. Antiplatelet therapy is adjusted according to ADP-mediated platelet inhibition: \<30% (hypercoagulable) prompts stepwise escalation (aspirin → aspirin + clopidogrel → aspirin + ticagrelor → aspirin + clopidogrel + ticagrelor); 30-86% (therapeutic range) continues the current regimen; \>86% (hypocoagulable) prompts de-escalation along the same sequence in reverse. Participants remaining outside the target range despite adjustment are referred to hematology. Protocol-guided adjustment continues through 6 months, after which management is transferred to the treating surgeon.

Treatment:

Drug: Ticagrelor

Drug: Clopidogrel

Diagnostic Test: Thromboelastography with Platelet Mapping

Drug: Aspirin

Diagnostic Test: Platelet Reactivity Testing