To study the effectiveness of low-dose rivaroxaban with aspirin in improving endothelial function in patients with symptomatic or stable PAD.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change in the proportion of patients with CAR constriction from baseline
(aspirin alone) to 3 months after adding low-dose rivaroxaban is the primary
outcome.
Secondary outcome
Secondary study parameters are:
- the change in endothelin-1 levels from baseline (aspirin alone) to 3 months
after adding low-dose rivaroxaban is the secondary outcome.
Other parameters are:
- Baseline values (gender, age, height, weight, smoking, comorbidities
(hyperlipidemia, hypertension, and diabetes) and medication use
- Major adverse cardiovascular events
- Major adverse limb events
- Major bleeding complications
- Medication adherence
Background summary
Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis,
causing patients to be at high risk of major adverse cardiovascular events and
major adverse limb events, including amputation. Therefore, clopidogrel or
aspirin, depending on national guidelines, is recommended as single
antiplatelet therapy when patients are symptomatic or have undergone
revascularization. Anticoagulant therapies have not shown to be superior in PAD
patients and have high rates of major bleedings. However, rivaroxaban (2.5 mg
twice a day), an oral factor Xa inhibitor, in addition to aspirin (100 mg once
a day) has shown to be effective in reducing morbidity and mortality from
coronary artery disease and major cardiovascular and limb events in patients
with stable peripheral or carotid artery disease compared to aspirin alone.
Although a higher rate of major bleeding was detected, the incidence of fatal
or critical organ bleedings was not increased.
Endothelial dysfunction is one of the first signs of atherosclerosis and is
present before clinical clinical symptoms appear. Endothelial dysfunction also
contributes to the progression of atherosclerosis and is related to major
cardiovascular events. The level of endothelial dysfunction can be measured
using the carotid artery reactivity (CAR) test. This test measures the CAR in
response to sympathic stimulation. An alternative source of information on
endothelial function and peripheral artery disease development is blood. A
marker with potential prognostic value is the serum endothelin-1 level. Serum
endothelin-1 levels correlate with atherosclerosis grade. These tests can also
be used to measure endothelial dysfunction in PAD patients and how a
combination of rivaroxaban and aspirin affects it.
Study objective
To study the effectiveness of low-dose rivaroxaban with aspirin in improving
endothelial function in patients with symptomatic or stable PAD.
Study design
Two clinical cohort studies.
Intervention
Aspirin 100mg once a day + 2.5 mg rivaroxaban twice a day (combination
therapy). The use of aspirin alone (100 mg once a day) during the run-in period
is used as reference.
Study burden and risks
In this prospective study, PAD patients will visit the hospital three times.
The first visit will be combined with a routine visit to the physician or
vascular laboratory. During the first visit, informed consent will be signed
and the patient can start the 30 days aspirin 'run-in period'. The second visit
will take place 30 days after the aspirin 'run-in' period, during which a blood
sample will be taken and the baseline CAR test will be performed. Thereafter,
patients can start the combination therapy of aspirin with rivaroxaban. Three
months after this combination therapy, new blood samples will be taken and the
CAR test will be repeated.
During the test, patients can experience some discomfort for a short amount of
time, which will immediately disappear once the tests are done.
Risks regarding the study drugs are the possible adverse effects of rivaroxaban
and aspirin.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Symptomatic or stable lower extremity peripheral artery disease patients
(Rutherford stages 1-6) with an indication for single antiplatelet therapy
according to international (ESC) guidelines
- 18 years or older
- Written informed consent
Exclusion criteria
- Patients having or at risk of major bleeding
- Patients with prosthetic valves
- Patients with a history of asthma attacks caused by salicylates
- Severe renal impairment (creatinine clearance <30 ml/min)
- Systemic treatment with CYP3A4 and/or P-glycoprotein inhibitors
(azole-antimyotics, HIV protease inhibitors)
- Concomitant treatment with other anticoagulants
- Concomitant treatment with methotrexate at a weekly dosage of >15 mg
- Pregnant or lactating
- Known hypersensitivity to aspirin or rivaroxaban
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 | EUCTR2019-003679-20-NL |
| ClinicalTrials.gov | NCT04218656 |
| CCMO | NL72452.091.19 |