Comparing NSAIDs and Coxibs for Patients Taking Aspirin

NSAIDs vs. Coxibs in the Presence of Aspirin: Effects on Platelet Function, Endothelial Function, and Biomarkers of Inflammation in Subjects With Rheumatoid Arthritis and Increased Cardiovascular Risk or Cardiovascular Disease

This study tests how two types of pain relievers, NSAIDs and Coxibs, work with aspirin in people with rheumatoid arthritis who are at risk for heart problems.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Inova Health Care Services (Academic / other)
• Drugs / interventions: methotrexate, prednisone
• Locations: 1 site (Falls Church, Virginia)
• Trial ID: NCT03699293 on ClinicalTrials.gov

What this trial studies

This interventional study aims to evaluate how NSAIDs and Coxibs interact with aspirin in patients with rheumatoid arthritis who are at high risk for cardiovascular disease. It will involve a randomized, crossover design where participants will receive both celecoxib and naproxen sodium after a run-in period with aspirin. Blood and urine samples will be collected to assess platelet function, inflammation biomarkers, and endothelial function. The study seeks to fill knowledge gaps regarding the cardiovascular safety of these medications in the presence of aspirin.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with rheumatoid arthritis and established cardiovascular disease or increased cardiovascular risk.

Not a fit: Patients currently taking anticoagulant therapy or other antiplatelet agents besides aspirin may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into safer pain management strategies for patients with rheumatoid arthritis and cardiovascular disease.

How similar studies have performed: Previous studies, such as the PRECISION trial, have shown promising results regarding the cardiovascular safety of celecoxib compared to other NSAIDs, indicating potential for success in this area.

Eligibility criteria

Inclusion Criteria:Qualified patients should have all 4 main criteria

1. Age 18-75 years of age for patients who regularly use NSAIDs.
2. Age 18-65 years of age for patients who do not regularly use NSAIDs
3. Able to give informed consent
4. 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:

1. Unstable angina, MI, CVA, CABG \<3 months from screening visit
2. Planned coronary, cerebrovascular, or peripheral revascularization
3. Undergone major surgery within 3 months prior to screening visit or has planned major surgery during the study period
4. Uncontrolled hypertension (SBP \>190, DBP \>100 mm Hg) during screening visit
5. Uncontrolled arrhythmia \< 3 months from screening visit
6. NYHA class III-IV heart failure or if available, ejection fraction ≤ 35 %
7. Within 6 months prior to screening visit, a history of ACS or hospitalization for heart failure
8. Oral corticosteroid, prednisone (or equivalent) \> 20 mg daily
9. Anticoagulation therapy
10. Antiplatelet therapy except for aspirin
11. GI ulceration \< 60 days before screening visit
12. GI bleeding, perforation, obstruction \< 6 months of screening visit
13. Inflammatory bowel disease, diverticulitis active \< 6 months of screening visit
14. AST, ALT, or BUN \>2x the upper limit normal (within 30 days prior to screening visit)
15. Creatinine level \>1.7 mg/dL in men, 1.5 mg/dL in women (within 30 days prior to screening visit)
16. On fluconazole, methotrexate, or lithium therapy
17. Malignancy \< 5 years before screening visit
18. Other known, active, significant GI, hepatic, renal, or coagulation disorders
19. Allergy, allergic-type reactions or hypersensitivity (e.g. asthma, urticaria, etc.) to any of the study medications and its components (i.e. sulfonamides)
20. 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
21. 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
22. Subjects who are legally institutionalized
23. Lactating females or females of childbearing potential except for those who are surgically sterile or postmenopausal-

Where this trial is running

Falls Church, Virginia

• Inova Heart and Vascular Institute — Falls Church, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Kevin Bliden, BS, MBA

Conditions Rheumatoid Arthritis; Cardiovascular Diseases