NSAIDs vs. Coxibs in the Presence of Aspirin

NCT03699293 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 17-2915
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rheumatoid Arthritis; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  End of 4-week aspirin run-in period and after completion of each 4-week treatment period.

Study Arms (2)

ASA and Celecoxib

ACTIVE COMPARATOR

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

ASA and Naproxen

ACTIVE COMPARATOR

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

celecoxib 200mg capsule DRUG

celecoxib 200mg twice a day for 4 weeks

Also known as: Celebrex

ASA and Celecoxib

naproxen sodium 550mg tablet DRUG

naproxen sodium 550mg twice a day for 4 weeks

Also known as: Aleve, Naprosyn

ASA and Naproxen

Aspirin 81mg tablet DRUG

81mg aspirin for 4 weeks in the run-in period, and for 8 weeks during treatment and crossover period

Also known as: Bayer Aspirin

ASA and Celecoxib; ASA and Naproxen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Platelet and Thrombosis Research, LLC: lead

Study Sites (1)

Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Cardiovascular Diseases

Interventions

Celecoxib; Naproxen; Tablets; Aspirin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Salicylates; Hydroxybenzoates; Phenols

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Sinai Center for Thrombosis Research and Drug Development

kbliden@lifebridgehealth.org

443-244-1497

Study Officials

• Paul Gurbel, MD

  LifeBridge Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Qualified 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 before the aspirin run-in period (baseline), 24±4 hrs after the last dose of aspirin in the run-in period, 24±4 hr after the last dose of the study drug in the first period and 24±4 hr after the last dose of the study drug in the second period. Assays for platelet function, biomarkers of inflammation and endothelial function will be performed at these time points

Study Record Dates

• First Submitted: September 21, 2018
• First Posted: October 9, 2018
• Study Start: September 22, 2018
• Primary Completion: December 1, 2022
• Study Completion: January 1, 2023
• Last Updated: May 14, 2026
• Results First Posted: May 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)