To assess whether and to what extent dual therapy clopidogrel 75 mg/acetylsalicylic acid 80 mg daily is superior to monotherapy clopidogrel 75 mg daily, in reducing the combined endpoint all-cause death and cardiovascular adverse events after one-…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is all-cause death and the occurrence of cardiovascular
adverse events after 1 year: re-intervention due to any restenosis or
re-occlusion or due to acute limb ischemia, the occurrence of any amputation,
cerebrovascular event, myocardial infarction, or cardiovascular death.
Secondary outcome
The secondary endpoint is the occurrence of all and major bleeding (following
the TIMI bleeding classification and BARC criteria), major adverse
cardiovascular events (MACE), and major adverse limb events (MALE). CYP2C19
polymorphisms will be determined to examine if non-responsiveness to
clopidogrel predicts outcome. The findings will not change clinical practice
within the course of the trial.
Background summary
Long-term antiplatelet therapy is the standard of care in patients with
peripheral arterial disease (PAD) because it reduces atherothrombotic events.
Despite this supportive treatment, the atherothrombotic events remain high in
PAD patients. In both coronary and cerebrovascular disease dual antiplatelet
therapy has proven to reduce atherothrombotic events. However, these results
cannot be extracted to PAD patients and there is an evidence gap in
antiplatelet therapy in PAD patients. The most recent guidelines on PAD show
discrepancies in the choice for dual or monotherapy after endovascular therapy.
Related to this, different surveys among vascular surgeons show different use
in antiplatelet prescription patterns. Current practice is based on the expert
opinion of the physician treating the patient that induces the risk of
incoherent choices.
Study objective
To assess whether and to what extent dual therapy clopidogrel 75
mg/acetylsalicylic acid 80 mg daily is superior to monotherapy clopidogrel 75
mg daily, in reducing the combined endpoint all-cause death and cardiovascular
adverse events after one-year follow-up in PAD patients who underwent
endovascular treatment.
Our hypothesis is that dual therapy with clopidogrel/aspirin will lead to a
lower occurrence of atherothrombotic events in patients following endovascular
treatment as compared to clopidogrel alone, in absence of risk for major
bleedings. This would lead to better clinical outcomes, increased quality of
life and an enhanced cost-effectiveness of treatment
Study design
Multicenter double-blind placebo-controlled randomized trial
Intervention
The intervention is comparing two groups: clopidogrel monotherapy (75 mg) plus
placebo daily versus dual therapy clopidogrel (75 mg)/aspirin (80 mg) daily.
Study burden and risks
This trial compares the two most commonly prescribed antiplatelet regimens in a
randomized fashion. However, only clopidogrel monotherapy is on-label. As such,
we anticipate that patients do not have a higher bleeding risk when
participating in the study than in general practice. A blood sample for CYP2C19
polymorphisms will be obtained during the intervention. This procedure bears
only the minimal risks while there is already access to the blood/vene/arteria
during the intervention. Patients do not benefit from participation, since the
results of the test will not influence the medical treatment plan. At last,
patiënts need to fill in questionnaires every 6 months.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
To be eligible to participate in this study, a subject must meet all of the
following criteria:
1. Lesions of the iliac, femoropopliteal, and/or below-the-knee (BTK) arteries;
2. At least one TASC lesion;
3. Rutherford (1-6) classes with an indication for an endovascular intervention;
4. Proficient understanding of the consequences of enrolment by the patient;
5. Written informed consent by the patient;
6. Age >= 45 years.
And:
7. Eligibility of lesions for;
a. Percutaneous transluminal angioplasty (PTA) or recanalization with or
without additional stenting based on prevailing guidelines, or;
b. Hybrid procedure with an endarterectomy of the common femoral artery and
additional iliac, femoral or tibial PTA, or;
c. A reintervention within 2 months due to a phased treatment.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Acute (limb) ischemia
2. Reported intolerance or hypersensitivity to the study medications
3. Use of anticoagulant therapy (DOACs or coumarin)
4. Use of non-steroidal anti-inflammatory drugs >2 weeks which cannot be
discontinued
5. Patients incompetent of understanding the consequences of enrolment in the
trial.
5.6. Patients with a reintervention due to restenosis/reocclusion within 2
months
7. Patients with a hybrid procedure other than endarterectomy of the common
femoral artery such as femoral bypass
8. Patients with coagulopathy
9. Patients with a peptic ulcer confirmed by an esophagogastroduodenoscopy in
their medical history
10. Patients who are pregnant/contemplating pregnancy/nursing.
11. Patients requiring dialysis
12. Patients with liver failure and at least one of the following criteria;
a. elevated INR value, or;
b. portal hypertension, or;
c. thrombocytopenia <50x10^9/L, or;
d. INR, portal tension, or platelet count are unknown.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-006611-29-NL |
| CCMO | NL80009.041.21 |