Duration of Dual Anti-Platelet Therapy in Chronic Limb Threatening Ischemia after Distal Revascularization: a randomized, double-blind trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Hopital Saint Joseph

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine whether one year of DAPT (aspirin 75-160 mg + clopidogrel 75 mg / day) compared to 1-month DAPT improve 1-year major amputation-free survival and overall mortality in patients with CLTI undergoing below-theknee endovascular therapy. All patients will also receive as standard of care rivaroxaban 2.5mg x 2.

Secondary objectives 1

1. To compare the effect of 12 months DAPT (aspirin 75-160 mg/day + clopidogrel 75 mg/day) to one month of DAPT followed by aspirin alone: 1. On the 12-month incidence of: • Each component of the combined primary endpoint (major amputation, overall mortality). • MALE, defined as reintervention on the index arterial segment [target lesion revascularization], acute limb ischemia or major amputation of the index limb. • MACE, defined as myocardial infarction, stroke or cardiovascular death. • Major bleeding events as defined by the ISTH (Safety endpoint) • Major bleeding and clinically relevant non major bleeding (Safety endpoint). 2. On the net clinical benefit (composite of deaths, MALE, MACE and major bleeding events); 1. On the change in quality of life in CLTI patients 2. On the 12-month costs, cost-effectiveness and cost-utility

Conditions and MedDRA coding

CLTI defined as Rutherford category 4 or 5

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 years
2. 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.
3. 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
4. Affiliation to a French Health Insurance system.
5. Patient able to understand and sign a written informed consent form.
6. - In women of childbearing potential: negative serum pregnancy test and use of adequate contraception.

Exclusion criteria 22

1. PAD Rutherford category 0, 1, 2, 3 or 6 (Rutherford 6 defined as severe ischemic ulcers or foot gangrene exceeding the digits)
2. Acute limb ischemia within one month prior to the qualifying revascularization
3. Platelet count < 100x109/L
4. Need for dual antiplatelet therapy for other reason than PAD
5. Need for concomitant treatment with anticoagulant (VKA or DOAC [except low dose rivaroxaban 2.5 mg x 2])
6. Known allergy or hypersensitivity to aspirin/clopidogrel
7. Exclusion criteria related to bleeding risks or systemic conditions:
8. • Medical 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);
9. • Any known hepatic disease associated with coagulopathy or bleeding risk
10. • Any 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);
11. • Confirmed acute coronary syndrome (ACS) within 30 days prior to randomization
12. • Major trauma or accidents within 30 days prior to randomization
13. • Any medically documented history of intracranial hemorrhage, stroke, or transient ischemic attack (TIA)
14. • Known active malignancy (as determined through review of medical history), excluding local skin cancer (basal or squamous cell carcinoma)
15. • Poorly controlled diabetes (at the discretion of the investigator)
16. • Severe uncontrolled hypertension (at the discretion of investigator)
17. • Previous (within 30 days) or concomitant participation in another clinical interventional study (drug or device)
18. 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)
19. Expected impossible follow-up or poor compliance
20. Patient deprived of liberty
21. Patient under tutorship, curatorship, or legal protection
22. Documented pregnancy or lactation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 14

1. Individual component of the combined primary endpoint: major amputation, overall mortality at 12 months.
2. 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)
3. 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
4. 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
5. 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)
6. Bleeding causing a fall in hemoglobin level of 2 g/dL or more
7. Bleeding leading to transfusion of two or more units of whole blood or red cells
8. 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),
9. Resulting in hospitalization or inducing an increase in the duration of hospitalization,
10. Prompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging)
11. Net clinical benefit outcome (composite outcome comprising deaths, MALE, MACE and major bleeding events)
12. Quality of life: VascuQol-6 and EQ-5D-5L scales
13. Costs at 12 months
14. Incremental cost-effectiveness and utility ratio (ICUR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Hopital Saint Joseph

Sponsor organisation

Fondation Hopital Saint Joseph

Address

185 Rue Raymond Losserand

City

Paris

Postcode

75014

Country

France

Scientific contact point

Organisation

Fondation Hopital Saint Joseph

Contact name

Pr. Joseph EMMERICH

Public contact point

Organisation

Fondation Hopital Saint Joseph

Contact name

Dr Delphine Chevalier

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications