Duration of Dual Anti-Platelet Therapy in Chronic Limb Threatening Ischemia After Distal Revascularization

NCT07512960 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 729_PALADIN-DAPTCLTI
• Study Type: interventional
• Target: 614
• Locations: 0 countries
• Sites: N/A

Brief Summary

Chronic limb threatening ischemia (CLTI) is defined as ischemic foot pain at rest or non-healing foot wounds that is attributable to severe peripheral arterial disease (PAD).Revascularization is the cornerstone of therapy to relieve ischemic pain, prevent limb loss and preserve patient autonomy. Revascularization procedures often involve below-the-knee arterial disease in CLTI population. Dual antiplatelet therapy (DAPT, with aspirin, and clopidogrel) is recommended for at least 1-month after peripheral angioplasty. However, the exact duration of this DAPT remains controversial. Angioplasty of below-the-knee arteries is often followed by a longer period of DAPT, 3-months to one-year, due to a high risk of arterial thrombosis/stenosis.It will be the first trial on duration of DAPT in patients with below-the-knee angioplasty for CLTI, the end-stage of PAD

Conditions

CLTI Defined as Rutherford Category 4 or 5

Keywords

Arterial angioplasty; Percutaneous transluminal angioplasty; Arterial thrombosis limb; Arterial thrombosis; Atherothrombosis

Outcome Measures

Primary Outcomes (1)

• Amputation-free survival at 12 months

  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.

  12 months

Study Arms (2)

CLOPIDOGREL

EXPERIMENTAL

11-months of clopidogrel 75 mg/day

Drug: Clopidogrel 75 mg/day

PLACEBO CLOPIDOGREL

PLACEBO COMPARATOR

11-months of placebo of clopidogrel

Other: Placebo Clopidogrel

Interventions

Clopidogrel 75 mg/day DRUG

After inclusion and randomization at one-month, the intervention group will receive clopidogrel 75 mg/day for 11 months and the control a placebo of clopidogrel/day for 11 months

CLOPIDOGREL

Placebo Clopidogrel OTHER

After inclusion and randomization at one-month, the control group will receive a placebo of clopidogrel/day for 11 months

PLACEBO CLOPIDOGREL

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• 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.
• Successful endovascular revascularization involving below-the-knee arteries (angioplasty/stenting) alone or combining above- and below-the-knee revascularization within the last 7 days prior to randomization
• Affiliation to a French Health Insurance system
• Patient able to understand and sign a written informed consent form.
• In women of childbearing potential: negative serum pregnancy test and use of adequate contraception.
• (According to CTFG guidelines, a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.)

You may not qualify if:

• PAD Rutherford category 0, 1, 2, 3 or 6 (Rutherford 6 defined as severe
• ischemic ulcers or foot gangrene exceeding the digits)
• Acute limb ischemia within one month prior to the qualifying revascularization
• Platelet count \< 100x109/L
• Need for dual antiplatelet therapy for other reason than PAD
• Need for concomitant treatment with anticoagulant (VKA or DOAC \[except low dose rivaroxaban 2.5 mg x 2\])
• Known allergy or hypersensitivity to aspirin/clopidogrel
• Severe hepatic impairment or any known hepatic disease associated with coagulopathy or bleeding risk;
• 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 and randomize the patient);
• Any medically documented history of intracranial hemorrhage, stroke, or transient ischemic attack (TIA);
• Known active malignancy (as determined through review of medical history), excluding local skin cancer (basal or squamous cell carcinoma);
• Poorly controlled diabetes (at the discretion of the investigator);
• Severe uncontrolled hypertension (at the discretion of investigator);
• Previous (within 30 days) or concomitant participation in another clinical interventional study (drug or device)
• 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)

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Related Publications (4)

• Abola MT, Bhatt DL, Duval S, Cacoub PP, Baumgartner I, Keo H, Creager MA, Brennan DM, Steg PG, Hirsch AT; REACH Investigators. Fate of individuals with ischemic amputations in the REACH Registry: three-year cardiovascular and limb-related outcomes. Atherosclerosis. 2012 Apr;221(2):527-35. doi: 10.1016/j.atherosclerosis.2012.01.002. Epub 2012 Jan 24.

  PMID: 22321872 RESULT

• Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Rother J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018 Mar 1;39(9):763-816. doi: 10.1093/eurheartj/ehx095. No abstract available.

  PMID: 28886620 RESULT

• Allemang MT, Rajani RR, Nelson PR, Hingorani A, Kashyap VS. Prescribing patterns of antiplatelet agents are highly variable after lower extremity endovascular procedures. Ann Vasc Surg. 2013 Jan;27(1):62-7. doi: 10.1016/j.avsg.2012.05.001. Epub 2012 Sep 12.

  PMID: 22981017 RESULT

• Anand SS, Caron F, Eikelboom JW, Bosch J, Dyal L, Aboyans V, Abola MT, Branch KRH, Keltai K, Bhatt DL, Verhamme P, Fox KAA, Cook-Bruns N, Lanius V, Connolly SJ, Yusuf S. Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial. J Am Coll Cardiol. 2018 May 22;71(20):2306-2315. doi: 10.1016/j.jacc.2018.03.008. Epub 2018 Mar 11.

  PMID: 29540326 RESULT

MeSH Terms

Conditions

Thrombosis

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Joseph Emmerich, Pr

  Hôpital Paris Saint Joseph

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph Emmerich, Pr

CONTACT

+33 1 44 12 37 64; jemmerich@ghpsj.fr

Naima SGHIOUAR, PhD

CONTACT

+330144123362; nsghiouar@ghpsj.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo and clopidogrel treatments are identical form and colour
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: clopidogrel 75 mg/day (intervention group), placebo of clopidogrel (control group

Study Record Dates

• First Submitted: March 27, 2026
• First Posted: April 6, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2030
• Study Completion (Estimated): November 30, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share