The objectives of this single site, randomized, crossover study is to evaluate the pharmacodynamic interactions between aspirin, NSAIDs and Coxibs with respect to platelet function, biomarkers of inflammation and endothelial function.
The relative cardiovascular safety of NSAIDs, particularly among patients with cardiovascular disease (CVD) or at higher CVD risk, has generated considerable concern among both patients and physicians because of knowledge gaps in the evidence relative to comparative safety and pharmacodynamic interactions between aspirin and NSAIDs. In the recently reported PRECISION trial, a moderate dose of celecoxib was found to be noninferior to ibuprofen or naproxen with respect to cardiovascular safety in patients with arthritis at increased CVD risk. At this time, no comparative prior data are available analyzing the effects of NSAIDs vs. Coxibs in the presence of aspirin on platelet function, biomarkers of inflammation and endothelial function. Thirty patients with rheumatoid arthritis who are at high cardiovascular (CV) risk or with established CV disease will be enrolled in the study. Patients taking anticoagulant therapy or any other antiplatelet agent other than aspirin will be excluded. Patients will be treated with immediate release 81mg aspirin for 4 weeks in the run-in period followed by randomization to celecoxib (200 mg bid) vs. naproxen sodium (550 mg bid) for 4 weeks and then cross over to the other drug for another 4 weeks. Blood and urine samples will be collected at baseline before the aspirin run in period, 24±4 hr after the last dose of aspirin in the run in period, 24±4 hr after the last dose of the first period study drug and 24±4 hr after the last dose of the second period study drug. Assays for platelet function, biomarkers of inflammation and endothelial function will be performed at these time points.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
celecoxib 200mg twice a day for 4 weeks
naproxen sodium 550mg twice a day for 4 weeks
81mg aspirin for 4 weeks in the run-in period, and for 8 weeks during treatment and crossover period
Sinai Hospital
Baltimore, Maryland, United States
Change in Arachidonic Acid (AA)-Induced Platelet Aggregation
Percent change in AA-induced platelet aggregation measured by light transmission aggregometry in platelet-rich plasma. Measurements were obtained at: * End of 4-week aspirin 81 mg daily run-in period (baseline) * After completion of the first 4-week treatment period following randomization * After completion of the second 4-week treatment period (crossover period) Aspirin 81 mg daily was administered during the run-in period and continued throughout the study. Each participant received celecoxib (200 mg twice daily) and naproxen sodium (550 mg twice daily) in two separate treatment periods in a randomized crossover design. The primary analysis was performed within-subject, comparing platelet aggregation during celecoxib exposure versus naproxen exposure.
Time frame: End of 4-week aspirin run-in period and after completion of each 4-week treatment period
Change in Collagen-induced Platelet Aggregation (%)
Percent change in collagen-induced platelet aggregation measured by light transmission aggregometry in platelet-rich plasma. Measurements were obtained at: * End of aspirin 81 mg daily run-in period (baseline) * After completion of the first 4-week treatment period following randomization * After completion of the second 4-week treatment period (crossover period) Aspirin 81 mg daily was continued throughout the study. Each participant received celecoxib (200 mg twice daily) and naproxen sodium (550 mg twice daily) in two separate treatment periods in a randomized crossover design. The primary analysis compared within-subject differences between celecoxib and naproxen exposure periods.
Time frame: End of 4-week aspirin run-in period and after completion of each 4-week treatment period
Change in Adenosine Diphosphate (ADP)-Induced Platelet Aggregation (%)
Percent change in ADP-induced platelet aggregation measured by light transmission aggregometry in platelet-rich plasma. Measurements were obtained at: * End of 4-week aspirin 81 mg daily run-in period (baseline) * After completion of the first 4-week treatment period following randomization * After completion of the second 4-week treatment period (crossover period) Aspirin 81 mg daily was administered during the run-in period and continued throughout the study. This was a randomized crossover study in which each participant received celecoxib (200 mg twice daily) and naproxen sodium (550 mg twice daily) in two separate treatment periods. The primary analysis compared within-subject differences in platelet aggregation between celecoxib exposure and naproxen exposure periods.
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Time frame: End of 4-week aspirin run-in period and after completion of each 4-week treatment period.
Change in Epinephrine-induced Platelet Aggregation (%)
Percent change in epinephrine induced platelet aggregation measured by light transmission aggregometry in platelet-rich plasma. Measurements were obtained at: * End of 4-week aspirin 81 mg daily run-in period (baseline) * After completion of the first 4-week treatment period following randomization * After completion of the second 4-week treatment period (crossover period) Aspirin 81 mg daily was administered during the run-in period and continued throughout the study. This was a randomized crossover study in which each participant received celecoxib (200 mg twice daily) and naproxen sodium (550 mg twice daily) in two separate treatment periods. The primary analysis compared within-subject differences in platelet aggregation between celecoxib exposure and naproxen exposure periods.
Time frame: End of 4-week aspirin run-in period and after completion of each 4-week treatment period.