Double-blind, triple dummy, parallel-group, randomized, six-month study to compare celecoxib (200 mg BID) with diclofenac SR (75 mg BID) plus omeprazole (20 mg QD) for gastrointestinal events in subjects with osteoarthritis and rheumatoid arthritis at high-risk of gastrointestinal adverse events - Not Applicable

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2004-001234-17-SE
• Date of registration: 27/10/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer AB
• Public title: Double-blind, triple dummy, parallel-group, randomized, six-month study to compare celecoxib (200 mg BID) with diclofenac SR (75 mg BID) plus omeprazole (20 mg QD) for gastrointestinal events in subjects with osteoarthritis and rheumatoid arthritis at high-risk of gastrointestinal adverse events - Not Applicable
• Scientific title: Double-blind, triple dummy, parallel-group, randomized, six-month study to compare celecoxib (200 mg BID) with diclofenac SR (75 mg BID) plus omeprazole (20 mg QD) for gastrointestinal events in subjects with osteoarthritis and rheumatoid arthritis at high-risk of gastrointestinal adverse events - Not Applicable
• Date of first enrolment: 22/05/2006
• Target sample size: 4402
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001234-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Parallel Group Triple Dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: Background drug will be Losec

Countries of recruitment

Czech Republic, Estonia, Greece, Ireland, Latvia, Lithuania, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion 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 <2 years will also require a urine pregnancy test at screening)

7. Female subjects of childbearing potential must be using effective contraception since the last date of their menses and continue to do so during the study period

8. Written informed consent obtained.

9. If required locally, negative fecal occult blood test (local standard) x 3.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

13. Previous participation in this study (subjects who fail screening due to HP infection may be considered for future enrollment in the trial if in the view of the investigator treatment for HP is deeme

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of osteoarthritis (OA) and/or rheumatoid arthritis (RA) in high GI risk patients
MedDRA version: 8.0 Level: LLT Classification code 10039073

Intervention(s)

Trade Name: celebra
Product Name: Celebrex
Product Code: not applicable
Pharmaceutical Form: Capsule*
INN or Proposed INN: Celecoxib
CAS Number: N/A
Other descriptive name: 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: Voltrarol SR
Product Code: Not Applicable
Pharmaceutical Form: Tablet
INN or Proposed INN: Diclofenac sodium
CAS Number: N/A
Current Sponsor code: Not applicable
Other descriptive name: sodium-[o-[(2,6-dichlorophenyl)-amino]-phenyl]-acetate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: Losec
Product Code: not applicable
Pharmaceutical Form: Capsule*
INN or Proposed INN: Omeprazole
CAS Number: N/A
Current Sponsor code: Not applicable
Other descriptive name: benzimidazole,5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1 H-benzimidazole
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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 ID(s)

2004-001234-17-GB

A3191084

Not Applicable