Clopidogrel for Chronic limb-threatening ischemia (CLTI) | Peripheral arterial disease

Inclusion criteria

• {"criterion_text":"- Age ≥18 years\n- Hospitalized patients with CLTI defined as Rutherford category 4 (ischemic rest pain) or 5 (minor tissue loss, non-healing ulcer, focal gangrene) evolving for > 2 weeks + one or more abnormal hemodynamic parameters: ankle-brachial index (ABI) <0.4 (using higher of the dorsalis pedis and posterior tibial arteries), absolute highest ankle pressure <50 mm Hg, absolute toe pressure <30 mm Hg.\n- Successful endovascular revascularization within 7-days involving below-the-knee arteries (angioplasty/stenting) alone or combining above- and below-the-knee revascularization within the last 7 days\n- Affiliation to a French Health Insurance system.\n- Patient able to understand and sign a written informed consent form.\n- \tIn women of childbearing potential: negative serum pregnancy test and use of adequate contraception."}

Exclusion criteria

• {"criterion_text":"- PAD Rutherford category 0, 1, 2, 3 or 6 (Rutherford 6 defined as severe ischemic ulcers or foot gangrene exceeding the digits)\n- •\tAny condition requiring dialysis or renal replacement therapy or a renal impairment at screening assessed with an estimated glomerular filtration rate <15 mL/min/1.73 m2. If a patient's eGFR is <30 mL/min/1.73 m2 prior to the procedure, it must remain >15 mL/min/1.73 m2 72 hours after the procedure to enroll the patient);\n- •\tConfirmed acute coronary syndrome (ACS) within 30 days prior to randomization\n- •\tMajor trauma or accidents within 30 days prior to randomization\n- •\tAny medically documented history of intracranial hemorrhage, stroke, or transient ischemic attack (TIA)\n- •\tKnown active malignancy (as determined through review of medical history), excluding local skin cancer (basal or squamous cell carcinoma)\n- •\tPoorly controlled diabetes (at the discretion of the investigator)\n- •\tSevere uncontrolled hypertension (at the discretion of investigator)\n- •\tPrevious (within 30 days) or concomitant participation in another clinical interventional study (drug or device)\n- Close affiliation with the investigational site; e.g., a close relative of the investigator, dependent person (e.g., employee or student of the investigational site)\n- Expected impossible follow-up or poor compliance\n- Acute limb ischemia within one month prior to the qualifying revascularization\n- Patient deprived of liberty\n- Patient under tutorship, curatorship, or legal protection\n- Documented pregnancy or lactation\n- Platelet count < 100x109/L\n- Need for dual antiplatelet therapy for other reason than PAD\n- Need for concomitant treatment with anticoagulant (VKA or DOAC [except low dose rivaroxaban 2.5 mg x 2])\n- Known allergy or hypersensitivity to aspirin/clopidogrel\n- Exclusion criteria related to bleeding risks or systemic conditions:\n- •\tMedical history or active clinically significant bleeding, lesions, or conditions within the last 6 months prior to randomization, considered to be a significant risk for major bleeding (this may include current medically confirmed gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, current or recent brain or spinal injury, known esophageal varices or major intraspinal or intracerebral vascular abnormalities);\n- •\tAny known hepatic disease associated with coagulopathy or bleeding risk"}

Primary endpoints

• {"endpoint_text":"- Amputation-free survival at 12 months, defined as time from randomization until major amputation (defined as above-the-ankle amputation) or death from any cause, whichever occurs first, for all subjects.","definition_or_measurement_approach":"Time from randomization until major amputation (defined as above-the-ankle amputation) or death from any cause, whichever occurs first; measured at 12 months."}

Secondary endpoints

• {"endpoint_text":"- Individual component of the combined primary endpoint: major amputation, overall mortality at 12 months.","definition_or_measurement_approach":"Measure each component separately at 12 months (major amputation; overall mortality)."}
• {"endpoint_text":"- MALE, a combined secondary endpoint at 12 months, defined by the occurrence of either one of the following items whichever occurs first: re-intervention on the index arterial segment (Target Lesion Revascularization/TLR), acute limb ischemia, major amputation of the index limb (above-the-ankle amputation)","definition_or_measurement_approach":"Composite measured as first occurrence of TLR, acute limb ischemia, or above-the-ankle major amputation within 12 months."}
• {"endpoint_text":"- MACE, a combined secondary endpoint at 12 months, defined by the occurrence of either of the following items whichever occurs first: myocardial infarction, stroke or cardiovascular death","definition_or_measurement_approach":"Composite measured as first occurrence of myocardial infarction, stroke, or cardiovascular death within 12 months."}
• {"endpoint_text":"- Change between inclusion and 12 months in quality of life using a disease-specific QoL Questionnaire commonly used in CLTI patients (VascuQoL-6 questionnaire) and a generic one, the EQ-5D-5L questionnaire","definition_or_measurement_approach":"Change from baseline to 12 months on VascuQoL-6 and EQ-5D-5L instruments."}
• {"endpoint_text":"- Fatal bleeding and/or symptomatic bleeding in a critical area/organ (such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome)","definition_or_measurement_approach":"Occurrence of fatal bleeding or symptomatic bleeding in critical areas/organs as listed."}
• {"endpoint_text":"- Bleeding causing a fall in hemoglobin level of 2 g/dL or more","definition_or_measurement_approach":"Bleeding event resulting in ≥2 g/dL drop in hemoglobin."}
• {"endpoint_text":"- Bleeding leading to transfusion of two or more units of whole blood or red cells","definition_or_measurement_approach":"Bleeding event requiring transfusion of ≥2 units of whole blood or red cells."}
• {"endpoint_text":"- Requiring intervention (medical practitioner-guided medical or surgical treatment to stop or treat bleeding, including temporarily or permanently discontinuing or changing the dose of a medication or study drug),","definition_or_measurement_approach":"Bleeding requiring medical or surgical intervention, including changes to medication/study drug."}
• {"endpoint_text":"- Resulting in hospitalization or inducing an increase in the duration of hospitalization,","definition_or_measurement_approach":"Bleeding resulting in hospitalization or prolongation of hospitalization."}
• {"endpoint_text":"- Prompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging)","definition_or_measurement_approach":"Bleeding prompting unscheduled healthcare visit and diagnostic testing."}
• {"endpoint_text":"- Net clinical benefit outcome (composite outcome comprising deaths, MALE, MACE and major bleeding events)","definition_or_measurement_approach":"Composite endpoint combining deaths, MALE, MACE and major bleeding events assessed at 12 months."}
• {"endpoint_text":"- Quality of life: VascuQol-6 and EQ-5D-5L scales","definition_or_measurement_approach":"Assessment using VascuQol-6 and EQ-5D-5L scales (change from baseline to 12 months)."}
• {"endpoint_text":"- Costs at 12 months","definition_or_measurement_approach":"Direct costs measured at 12 months."}
• {"endpoint_text":"- Incremental cost-effectiveness and utility ratio (ICUR)","definition_or_measurement_approach":"Economic evaluation calculating ICUR at 12 months."}

France

Earliest CTIS Part Ii Submission Date

02-02-2026

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

31

Number Of Sites

24

Number Of Participants

614

Primary sponsor

Full Name

Fondation Hopital Saint Joseph

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France