Treatment of osteoarthritis (OA) and/or rheumatoid arthritis (RA) in high GI risk patients MedDRA version: 8.0 Level: LLT Classification code 10039073
Conditions
Interventions
Trade Name: Celebrex
Product Name: Celebrex
Product Code: not applicable
Pharmaceutical Form: Capsule*
INN or Proposed INN: Celecoxib
Sponsors
Pfizer Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male and female subjects who meet all criteria listed below will be included in the study. 1. Outpatient or inpatient 2. Subjects with a clinical diagnosis of OA or RA. (Subjects should have a clinical diagnosis of OA or RA based on their clinical history, previous or current signs, symptoms or investigations or if the view of the investigator the subject has OA or RA based on his/her clinical judgment or the ACR criteria) 3. Subjects who are expected to require regular anti-inflammatory therapy for arthritis symptom management 4. Subjects must be aged = 60 years with or without a history of GD ulceration; or be of any age = 18 years and have had documented in clinical notes evidence of GD ulceration 90 days or more prior to the screening visit The following are acceptable as documentation of a previous history of GD ulceration: investigational site clinical notes/ endoscopy or radiographic report; documentation provided by another institution or the subject’s primary care provider; verbal confirmation by another institution or the subject’s primary care provider. Verbal confirmation by the subject alone without corroboration is not sufficient. History of GD ulceration includes both uncomplicated and complicated events. Subjects who have a history of complicated ulcer disease are most at risk of the development of further serious events. In considering subjects with previous complicated ulcers for inclusion into the trial investigators must carefully weigh the balance of benefit: risk for inclusion of the subject into the trial and discuss this with the subject as per the informed consent 5. Screening tests are negative for H pylori (serology, 13C or 14C breath test or rapid urease/histology or fecal antigen). Subjects who test positive on serology must have active infection excluded using a second methodology 6. Female subjects of childbearing potential must not be pregnant or lactating at screening and must have a negative urine pregnancy test at screening (women post-menopausal for =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the study: 1. GI ulcer hemorrhage or active GD ulceration less than 90 days prior to screening visit 2. Current use of anticoagulant agents, lithium, disease modifying anti-rheumatic drugs (DMARDs- unless on stable dose for at least 12 weeks), corticosteroids (dose equivalent of prednisolone/ prednisone =10mg daily allowable if on stable dose for at least 12 weeks), NSAIDs, proton pump inhibitors (PPIs – other than use of study medication), sucralfate, misoprostol or regular use of a histamine-2 receptor antagonist (H2RAs; > 3 days/week). Current H2RAs use intermittently (no more than 3 days/week) for dyspepsia is allowed; antacids are allowed. Subjects receiving PPI, COX-2 specific inhibitor or NSAID therapy at the screening visit are allowable into the trial, if these treatments are discontinued at the time of screening and the other inclusion/ exclusion criteria are met. 3. Subjects on iron replacement therapy (or a dose >15mg elemental iron/day) or taking iron supplements for deficiency prevention (a dose =15mg elemental iron/day) due to anemia or any other reason will not be included in the study. However, subjects taking a dietary supplement not containing iron can be included. 4. Subjects using aspirin, including low dose aspirin, and subjects not using low dose aspirin but considered by the investigator to be indicated for cardiovascular prophylaxis with low dose aspirin. {If necessary, locally accepted cardiovascular risk calculators should be used. As an example a greater than 10% 10 year risk for serious cardiovascular events should be assessed for therapy with aspirin; and if indicated, patients should be excluded from the trial. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update (Circulation. 2002;106:388-391.)} 5. Subjects using other antiplatelet agents (ticlopidine, clopidogrel, dipyridamole) 6. Subjects with a history of established ischemic heart disease (e.g. myocardial infarction, stable angina, unstable angina), peripheral arterial disease and/or cerebrovascular disease (e.g. ischemic or hemorrhagic stroke, transient ischemic attack), as well as subjects with previous revascularization procedure to coronary, carotid, cerebral, renal, aortic or peripheral arterial vasculature. The investigator should exclude subjects with ischemic or other electrocardiographic modifications that in his/her opinion are clinically significant. 7. History of gastric or duodenal surgery other than patch repair/ over sew 8. Presence of erosive esophagitis, gastric-outlet obstruction 9. Malignancy or history of malignancy other than surgically removed basal cell carcinoma. Subjects with successfully treated malignancy and no history or evidence of recurrent disease within 5 years prior to enrollment may be included in the study 10. Pregnant or lactating women, or women of childbearing potential including women less than two years post-menopausal not using an acceptable method of contraception 11. Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study 12. Current or history of alcohol and/or any other substance abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether celecoxib is superior to combined therapy with diclofenac SR and omeprazole for the incidence of clinically significant upper and/or lower GI events (CSULGIEs) in high GI risk subjects with OA and/or RA.;Secondary Objective: To determine safety and tolerability of celecoxib in subjects treated with celecoxib compared to treatment with diclofenac SR plus omeprazole in subjects with OA and/or RA.; Primary end point(s): The primary endpoint of this study is the incidence of clinically significant upper and/or lower GI events (CSULGIEs). For the purposes of this trial CSULGIEs are considered any event that in clinical practice would impact the subject in terms of inpatient or outpatient investigation for GI pathology with blood loss or other serious complication. CSULGIEs are a composite of any of the following (adjudicated by GI Events Adjudication Committee): · Gastroduodenal hemorrhage · Gastric outlet obstruction · Gastroduodenal, small bowel or large bowel perforation · Small bowel hemorrhage · Large bowel hemorrhage · Clinically significant anemia of defined GI origin · Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage · Clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. | — |
Countries
Belgium, Czech Republic, Estonia, Germany, Greece, Ireland, Latvia, Lithuania, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed