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NSAIDs vs. Coxibs in the Presence of Aspirin

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ClinicalTrials.gov Identifier: NCT03699293
Recruitment Status : Recruiting
First Posted : October 8, 2018
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
Inova Health Care Services

Tracking Information
First Submitted Date  ICMJE September 21, 2018
First Posted Date  ICMJE October 8, 2018
Last Update Posted Date October 8, 2018
Actual Study Start Date  ICMJE September 22, 2018
Estimated Primary Completion Date September 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
Platelet aggregation [ Time Frame: 12 weeks ]
Change in platelet aggregation by light transmittance aggregometry between treatment groups
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
  • Serum TxB2 [ Time Frame: 12 weeks ]
    Changes in serum TxB2 between treatment groups
  • Urine thromboxane [ Time Frame: 12 weeks ]
    Changes in urine thromboxane between treatment groups
  • Urine 8 iso prostaglandin [ Time Frame: 12 weeks ]
    Changes in urine 8 iso prostaglandin between treatment groups
  • Endothelial function by EndoPAT [ Time Frame: 12 weeks ]
    Changes in endothelial function by EndoPAT (Endothelial Peripheral Arterial Tone) between treatment groups
  • Soluble markers of circulating adhesion molecules (VCAM, ICAM). [ Time Frame: 12 weeks ]
    Changes in soluble markers of circulating adhesion molecules (VCAM, and ICAM) between treatment groups
  • hsCRP [ Time Frame: 12 weeks ]
    Changes in hsCRP between treatment groups
  • Oxidized LDL [ Time Frame: 12 weeks ]
    Changes in Oxidized LDL between treatment groups
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NSAIDs vs. Coxibs in the Presence of Aspirin
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
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
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Rheumatoid Arthritis
  • Cardiovascular Diseases
Intervention  ICMJE
  • Drug: celecoxib 200mg capsule
    celecoxib 200mg twice a day for 4 weeks
    Other Name: Celebrex
  • Drug: naproxen sodium 550mg tablet
    naproxen sodium 550mg twice a day for 4 weeks
    Other Names:
    • Aleve
    • Naprosyn
  • Drug: Aspirin 81mg tablet
    81mg aspirin for 4 weeks in the run-in period, and for 8 weeks during treatment and crossover period
    Other Name: Bayer Aspirin
Study Arms  ICMJE
  • 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)
    Interventions:
    • 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)
    Interventions:
    • Drug: naproxen sodium 550mg tablet
    • Drug: Aspirin 81mg tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 4, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 24, 2019
Estimated Primary Completion Date September 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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-
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kevin Bliden, BS, MBA (703) 776-7702 kevin.bliden@inova.org
Contact: Emiliya Bakalska, BA (410) 367-2592 emiliya.bakalska@inova.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03699293
Other Study ID Numbers  ICMJE 17-2915
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan to share IPD.
Responsible Party Inova Health Care Services
Study Sponsor  ICMJE Inova Health Care Services
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kevin Bliden, BS, MBA Inova Health Care Services
PRS Account Inova Health Care Services
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP