Celecoxib, Ibuprofen and the Antiplatelet Effect of Aspirin

Osteoarthritis Clinical Trial

Official title:

A Placebo-Controlled, Double-Blind, Randomized Study of the Potential Interaction Between Aspirin and Ibuprofen or Celecoxib.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00565500
• Other study ID #: 635-IFL-0508-017
• Secondary ID: N49-98-71-900
• Status: Completed
• Phase: Phase 4
• First received: November 29, 2007
• Last updated: November 29, 2007
• Start date: April 2003
• Est. completion date: April 2005

Study information

• Verified date: November 2007
• Source: G. d'Annunzio University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Study design: Single center, placebo-controlled, double blind, parallel groups. To evaluate the potential interaction between aspirin and ibuprofen or celecoxib in patients with osteoarthritis (OA) and documented stable ischemic heart disease, a total of 24 patients chronically treated with aspirin will be randomly assigned to one of the 3 treatment groups: 1) celecoxib 200 mg bid; 2) ibuprofen 600 mg tid; 3) placebo.

Description:

Patients with arthritis and vascular disease may receive both NSAIDs and lowdose aspirin for the secondary prevention of important vascular events. The use of COX-2 inhibitors may have the potential advantage vs. nonselective NSAIDs in reducing the probability of interfering with permanent inactivation of COX-1 platelet by low-dose aspirin, in this setting. In fact, recent studies suggest that the likelihood of COX-inhibitors to present this pharmacodynamic interaction is inversely related to their COX-2 selectivity. Thus, differently from the non-selective NSAID ibuprofen, prior administration of the selective COX-2 inhibitor rofecoxib, does not antagonize the irreversible inhibition induced by aspirin in healthy subjects. Aim of this study is to determine whether celecoxib given at therapeutic dose at steady state alters the antiplatelet activity of low-dose aspirin, in comparison with ibuprofen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. male or female, age 18-75;

2. subjects with osteoarthritis and documented stable ischemic heart disease;

3. the patient is on long-term aspirin prophylaxis for the ischemic condition;

4. the patient requires or is eligible for chronic treatment with an antiinflammatory and/or analgesic drugs given to control osteoarthritis symptoms;

5. female subjects of childbearing potential must have a negative pregnancy test, use adequate contraception during the study and not be lactating;

6. written informed consent before undergoing any study procedure.

Exclusion Criteria:

1. active gastrointestinal disease (e.g. Crohn's disease or ulcerative colitis) or any evidence of concomitant disease which may lead to early termination of the study;

2. history of active peptic ulceration, gastrointestinal bleeding, esophageal, gastric or duodenal ulcer;

3. known hypersensitivity to COX-2 inhibitors, analgesics, antipyretics, sulfonamides or NSAIDs;

4. treatment with any investigational drug within the previous 30 days;

5. previous participation in this study;

6. evidence of neoplasm or any other severe disease of any organ, including any psychiatric illness;

7. clinically relevant deviations from the normal range in laboratory tests;

8. recent history or suspicion of alcohol abuse or drug addiction;

9. subjects unlikely to be collaborative or to give reliable answers;

10. pregnancy or lactation; female or childbearing potential without a clinical accepted contraceptive method;

11. any severe pathology that can interfere with the treatment or the clinical or instrumental tests of the trial;

12. intake of antiaggregant, anticoagulant, diuretic, beta-blocker, ACE- inhibitor, lithium, methotrexate, cimetidine, digoxin;

13. contraindications to NSAIDs.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemic Heart Disease
• Myocardial Ischemia
• Osteoarthritis

Intervention

Drug:
• celecoxib
celecoxib capsules 200 mg bid for 1 week
• ibuprofen
ibuprofen tablets 600 mg tid for 1 week
• placebo
placebo capsules tid for 1 week

Locations

Country	Name	City	State
Italy	Ce.S.I., Center of Excellence on Aging, G. d'Annunzio University	Chieti	CH

Sponsors (2)

Lead Sponsor	Collaborator
University of Chieti	Pfizer

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, Vyas SN, FitzGerald GA. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001 Dec 20;345(25):1809-17. — View Citation

FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. Review. — View Citation

Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest. 1982 Jun;69(6):1366-72. — View Citation

Patrono C, Coller B, Dalen JE, FitzGerald GA, Fuster V, Gent M, Hirsh J, Roth G. Platelet-active drugs : the relationships among dose, effectiveness, and side effects. Chest. 2001 Jan;119(1 Suppl):39S-63S. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum thromboxane (TX)B2		1 week	No
Secondary	urinary 11-dehydro-thromboxane (TX)B2, arachidonic acid- and ADP-induced platelet aggregation by Born's aggregometer, whole-blood aggregation in the platelet function analyzer (PFA) system, LPS-stimulated prostaglandin(PG)E2		1 week	No