TerminatedNCT03699293Updated May 14, 2026Results posted

NSAIDs vs. Coxibs in the Presence of Aspirin

A Phase 4 interventional study of celecoxib 200mg capsule and naproxen sodium 550mg tablet in Rheumatoid Arthritis and Cardiovascular Diseases, sponsored by Platelet and Thrombosis Research, LLC. Terminated at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-14.

Sponsored by Platelet and Thrombosis Research, LLC · Phase 4, Interventional, and Basic science

Why this study was terminated

Our group moved from Inova Heart and Vascular institute to Sinai Hospital with Platelet and Thrombosis, LLC taking over sponsorship. Study was then IRB approved at Sinai on March, 2020 but closed prior to any additional enrolment due to COVID.

Phase: Phase 4
Study type: Interventional
Enrollment: 8
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Rheumatoid Arthritis
Cardiovascular Diseases

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In context

Arthritis, Rheumatoid

2,888 studies on the registry are indexed under Arthritis, Rheumatoid; 390 are open to participants now.

This study's enrollment of 8 is below the median of 94 across 1,984 interventional studies indexed under Arthritis, Rheumatoid.

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Lead sponsor

This is the only study on the registry with Platelet and Thrombosis Research, LLC as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:Qualified patients should have all 4 main criteria

Age 18-75 years of age for patients who regularly use NSAIDs.
Age 18-65 years of age for patients who do not regularly use NSAIDs
Able to give informed consent
Subjects with CVD or increased CV risk. Please see definitions for each criteria below:
- Increased CV risk (Subjects should have at least 3 of the following)
  - > 55 years of age
  - Hypertension
  - Dyslipidemia (LDL > 160 mg/dL or HDL \< 40 mg/dL in females and \< 35 mg/dL in males or subjects currently receiving lipid lowering therapy as standard of care (i.e. statin drugs, prescription ω 3-acid ethyl esters, fibrates or prescription niacin [≥1,000 mg/d])
  - Family history of premature CV disease (MI, angina pectoris, heart failure, cardiac death or coronary revascularization, stroke, carotid endarterectomy, or other arterial surgery or angioplasty for atherosclerotic vascular disease in a parent, grandparent, or sibling with symptom onset or diagnosis before age 55 y for males and 65 y for females)
  - Current smoker
  - Left ventricular hypertrophy
  - Documented ankle brachial index of \<0.9
  - History of microalbuminuria, urine protein-creatinine ratio of >2
- CV disease (defined as one of the following):
  - Calcium score of >0
  - ≥ 50 % occlusion of a coronary artery by angiography
  - ≥ 50 % occlusion of a carotid artery by angiography or ultrasound
  - History of stable angina
  - Symptomatic peripheral arterial disease
  - Prior MI, unstable angina, percutaneous coronary intervention, CABG, TIA, ischemic stroke, carotid endarterectomy, or other arterial surgery or angioplasty, which have occurred > 3 months prior to screening visit
  - Diabetes Mellitus type 1 or 2 (considered a CV disease equivalent).
- Clinical diagnosis of rheumatoid arthritis, as determined by individual patient and physician, requiring daily treatment with NSAIDs.

Exclusion Criteria: Subjects with any of the following criteria will be excluded from this study:

Unstable angina, MI, CVA, CABG \<3 months from screening visit
Planned coronary, cerebrovascular, or peripheral revascularization
Undergone major surgery within 3 months prior to screening visit or has planned major surgery during the study period
Uncontrolled hypertension (SBP >190, DBP >100 mm Hg) during screening visit
Uncontrolled arrhythmia \< 3 months from screening visit
NYHA class III-IV heart failure or if available, ejection fraction ≤ 35 %
Within 6 months prior to screening visit, a history of ACS or hospitalization for heart failure
Oral corticosteroid, prednisone (or equivalent) > 20 mg daily
Anticoagulation therapy
Antiplatelet therapy except for aspirin
GI ulceration \< 60 days before screening visit
GI bleeding, perforation, obstruction \< 6 months of screening visit
Inflammatory bowel disease, diverticulitis active \< 6 months of screening visit
AST, ALT, or BUN >2x the upper limit normal (within 30 days prior to screening visit)
Creatinine level >1.7 mg/dL in men, 1.5 mg/dL in women (within 30 days prior to screening visit)
On fluconazole, methotrexate, or lithium therapy
Malignancy \< 5 years before screening visit
Other known, active, significant GI, hepatic, renal, or coagulation disorders
Allergy, allergic-type reactions or hypersensitivity (e.g. asthma, urticaria, etc.) to any of the study medications and its components (i.e. sulfonamides)
History of any disease of condition that, in the opinion of the investigator would place the subject at an unacceptable risk to participate in this study
Any clinically relevant abnormal findings in physical examination, vital signs, or previous laboratory works that, in the opinion of the investigator, may compromise the safety of the subject to participate
Subjects who are legally institutionalized
Lactating females or females of childbearing potential except for those who are surgically sterile or postmenopausal-

Study design

Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 8 participants (actual)

Study arms

Active comparator
ASA and Celecoxib
Take celecoxib 200mg capsule twice a day and aspirin 81mg tablet once a day for 4 weeks (after completion of the run-in period)
Drug: celecoxib 200mg capsule · Drug: Aspirin 81mg tablet
Active comparator
ASA and Naproxen
Take naproxen sodium 550mg tablet twice a day and aspirin 81mg tablet once a day (after completion of the run-in period)
Drug: naproxen sodium 550mg tablet · Drug: Aspirin 81mg tablet

Interventions

Drugcelecoxib 200mg capsule
celecoxib 200mg twice a day for 4 weeks
Also known as: Celebrex
Drugnaproxen sodium 550mg tablet
naproxen sodium 550mg twice a day for 4 weeks
Also known as: Aleve, Naprosyn
DrugAspirin 81mg tablet
81mg aspirin for 4 weeks in the run-in period, and for 8 weeks during treatment and crossover period
Also known as: Bayer Aspirin

What researchers measure

Primary outcomes

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.
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.

Results

Posted May 14, 2026

Participant flow

Aspirin run-in (Baseline)

Participant flow — Aspirin run-in (Baseline)
Milestone	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA + Naproxen Sodium , 3) ASA + Celecoxib
Started	4	4
Completed	3	3
Not completed	1	1
Withdrew: Withdrawal by subject	1	1

Treatment Period 1 (Post Randomization )

Participant flow — Treatment Period 1 (Post Randomization )
Milestone	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA + Naproxen Sodium , 3) ASA + Celecoxib
Started	3	3
Completed	3	3
Not completed	0	0

Treatment Period 2 (Crossover)

Participant flow — Treatment Period 2 (Crossover)
Milestone	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA + Naproxen Sodium , 3) ASA + Celecoxib
Started	3	3
Completed	3	2
Not completed	0	1
Withdrew: Adverse event	0	1

Outcome measures

PrimaryChange 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
Reported as:: Mean · Percent Aggregation (%)

Change in Arachidonic Acid (AA)-Induced Platelet Aggregation
Percent Aggregation (%)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA + Naproxen Sodium, 3) ASA + Celecoxib
End of 4-week aspirin (run in period)	2.5 ± 0.7	3.3 ± 4.9
End of Treatment period 1 (post randomization)	1.4 ± 1.6	3 ± 0
End of Treatment period 2(Crossover)	6.5 ± 7.8	31.5 ± 34.6

PrimaryChange 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
Reported as:: Mean · Percent Aggregation (%)

Change in Collagen-induced Platelet Aggregation (%)
Percent Aggregation (%)	ASA Lead in Followed by ASA + Celecoxib, and Then Crossover to ASA+ Naproxen Arm.	ASA and Naproxen
Aspirin run-in period	55.3 ± 20.4	68.0 ± 18.4
End of Treatment Period 1( post randomization)	-0.3 ± 3.7	-12.5 ± 14.8
End of Treatment Period 2 ( Crossover)	-10.7 ± 8.2	-6 ± 3.1

PrimaryChange 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.

Time frame:: End of 4-week aspirin run-in period and after completion of each 4-week treatment period.
Reported as:: Mean · Percent Aggregation (%)

Change in Adenosine Diphosphate (ADP)-Induced Platelet Aggregation (%)
Percent Aggregation (%)	ASA and Celecoxib	ASA and Naproxen
Aspirin Run in Period	60.3 ± 11.0	64.0 ± 14.4
End of Treatment period 1 (Post randomization)	-27 ± 22	0.5 ± 0.7
End of Treatment period 2 (Crossover)	-6.6 ± 6.7	-3 ± 8.5

PrimaryChange 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.
Reported as:: Mean · Percent Aggregation (%)

Change in Epinephrine-induced Platelet Aggregation (%)
Percent Aggregation (%)	ASA and Celecoxib	ASA and Naproxen
Aspirin run-in period	23.3 ± 6.8	10.5 ± 3.5
End of Treatment 1 (Post randomization)	5.3 ± 3.0	2.5 ± 3.5
End of Treatment 2 (Crossover)	36.0 ± 21.2	19.5 ± 20.0

Adverse events

Collected over 12 weeks from enrollment. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Aspirin Run in Period	0/8 (0%)	0/8 (0%)	0/8 (0%)
ASA + Celecoxib Treatment Period	0/6 (0%)	0/6 (0%)	0/6 (0%)
ASA + Naproxen Sodium Treatment Period	0/6 (0%)	0/6 (0%)	1/6 (16.7%)

Most frequent other events

Most frequent other events
Event	Aspirin Run in Period	ASA + Celecoxib Treatment Period	ASA + Naproxen Sodium Treatment Period
Abdominal indigestionGastrointestinal disorders	0/8	0/6	1/6
Acute Gastritis [1]Gastrointestinal disorders	0/8	0/6	1/6
Carpal tunnel syndrome [1]Nervous system disorders	0/8	0/6	1/6
Vaginal pain [1]Reproductive system and breast disorders	0/8	0/6	1/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA +Sodium , 3) ASA + Celecoxib	Total
<=18 years	0	0	0
Between 18 and 65 years	3	3	6
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA +Sodium , 3) ASA + Celecoxib	Total
Mean	30 ± 38	56.0 ± 1.4	45.4 ± 15.0

Sex: Female, Male
Sex: Female, Male(Participants)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA +Sodium , 3) ASA + Celecoxib	Total
Female	2	3	5
Male	1	0	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA +Sodium , 3) ASA + Celecoxib	Total
American Indian or Alaska Native	0	0	0
Asian	1	0	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	0	1
White	1	3	4
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	Sequence 1: 1) Aspirin Run in Period, 2) ASA + Celecoxib, 3) ASA + Naproxen Sodium	Sequence 2: 1) Aspirin Run in Period, 2) ASA +Sodium , 3) ASA + Celecoxib	Total
United States	3	3	6

Study locations

1 site

Sinai Hospital
Baltimore, Maryland 21215, United States

References and documents

Study documents

Protocol and statistical analysis plan · Feb 12, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — No plan to share IPD.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 14, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03699293
Lead sponsor: Platelet and Thrombosis Research, LLC
Responsible party: Sponsor
First posted: Oct 9, 2018
Start date: Sep 22, 2018
Primary completion: Dec 1, 2022
Completion: Jan 1, 2023
Results posted: May 14, 2026
Last update: May 14, 2026

Study contacts

Paul Gurbel, MD

principal investigator · LifeBridge Health

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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