Clinical trial NCT00153660: Celecoxib Versus Naproxen for Prevention of Recurrent Ulcer Bleeding in Arthritis Patients
Official title: A Double-blind Randomized Comparison of Celecoxib Plus Esomeprazole Versus Naproxen Plus Esomeprazole for Prevention of Recurrent Ulcer Bleeding in Patients With Arthritis and Cardiothrombotic Diseases (NSAID#8 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis
Cardiovascular Diseases
Cerebrovascular Disorders
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2005-09-12
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recurrent ulcer bleeding within 18 months according to pre-specified criteria
timeFrame: 18 months
Secondary outcomes:
measure: patients' global assessment of arthritis
timeFrame: 18 months
measure: major CV events according to the Antithrombotic Trialists' criteria
timeFrame: 18 months
measure: non-fatal myocardial infarction
timeFrame: 18 months
measure: non-fatal stroke
timeFrame: 18 months
measure: death from a vascular cause
timeFrame: 18 months
Other outcomes:
Locations:
city: Shatin
country: China
facility: Endoscopy Center, Prince of Wales Hospital
state: Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Francis K Chan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chan FKL, Ching JYL, Tse YK, Lam K, Wong GLH, Ng SC, Lee V, Au KWL, Cheong PK, Suen BY, Chan H, Kee KM, Lo A, Wong VWS, Wu JCY, Kyaw MH. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial. Lancet. 2017 Jun 17;389(10087):2375-2382. doi: 10.1016/S0140-6736(17)30981-9. Epub 2017 Apr 11.