Arthritis, Cardiovascular Diseases, Cerebrovascular Disorders
Conditions
Brief summary
The aim of this study is to compare celecoxib plus a PPI (esomeprazole) versus naproxen plus a PPI (esomeprazole) in preventing recurrent ulcer bleeding in arthritis patients with a history of ulcer bleeding who require concomitant ASA. We hypothesized that among patients with a history of ulcer bleeding who require concomitant ASA, celecoxib plus esomprazole would be superior to naproxen plus esomeprazole for the prevention of recurrent ulcer bleeding.
Detailed description
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly consumed drugs worldwide for the relief of pain and arthritis. However, the use of NSAIDs increases the risk of ulcer bleeding by 4-fold. Current evidence indicates that combination of conventional NSAIDs and a proton pump inhibitor (PPI) reduces the risk of ulcer complications. The alternative strategy is to replace conventional, non-selective NSAIDs with NSAIDs selective for cyclooxygenase-2 (COX-2 inhibitors). Recently, there are concerns about the cardiovascular safety of COX-2 inhibitors and conventional NSAIDs. Because of such concern, patients requiring anti-inflammatory analgesics who have cardiovascular risk factors (e.g. smoking, hypertension, hyperlipidemia, diabetes) should receive prophylactic low-dose aspirin. However, concomitant low-dose aspirin negates the gastric sparing effect of COX-2 inhibitors and augments the gastric toxicity of nonselective NSAIDs. Thus, gastroprotective agents such as PPIs should be co-prescribed to patients with high ulcer risk who are taking aspirin plus a COX-2 inhibitor or a nonselective NSAID.
Interventions
Celecoxib 100 mg bd
Naproxen 500 mg bd
Sponsors
Study design
Eligibility
Inclusion criteria
1. age \>18, 2. a history of endoscopically proven gastroduodenal ulcer bleeding, 3. H. pylori negative 4. a history of cardiothrombotic disease requiring ASA, and 5. anticipated regular use of NSAIDs for the duration of trial
Exclusion criteria
1. concomitant use of anticoagulants; 2. a history of gastric or duodenal surgery other than a patch repair; 3. the presence of erosive esophagitis, 4. gastric outlet obstruction, 5. renal failure (defined by a serum creatinine level of more than 200 umol/L), 6. pregnancy, 7. terminal illness, or 8. cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrent ulcer bleeding within 18 months according to pre-specified criteria | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| patients' global assessment of arthritis | 18 months |
| major CV events according to the Antithrombotic Trialists' criteria | 18 months |
| non-fatal myocardial infarction | 18 months |
| non-fatal stroke | 18 months |
| death from a vascular cause | 18 months |
Countries
China