Celecoxib Versus Naproxen for Prevention of Recurrent Ulcer Bleeding in Arthritis Patients

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)

Sponsors

Lead Sponsor: Chinese University of Hong Kong

Source Chinese University of Hong Kong
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.

Overall Status Completed
Start Date June 2005
Completion Date December 2016
Primary Completion Date November 2014
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Recurrent ulcer bleeding within 18 months according to pre-specified criteria 18 months
Secondary Outcome
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
Enrollment 514
Condition
Intervention

Intervention Type: Drug

Intervention Name: Celecoxib(drug)

Description: Celecoxib 100 mg bd

Arm Group Label: NSAID #1

Other Name: Celebrex

Intervention Type: Drug

Intervention Name: Naproxen(drug)

Description: Naproxen 500 mg bd

Arm Group Label: NSAID #2

Other Name: Naprosyn

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Francis K Chan, MD Principal Investigator Chinese University of Hong Kong
Location
Facility: Endoscopy Center, Prince of Wales Hospital
Location Countries

China

Verification Date

December 2016

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Chinese University of Hong Kong

Investigator Full Name: Francis KL Chan

Investigator Title: Professor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: NSAID #1

Type: Active Comparator

Description: Celecoxib and Naproxen Placebo

Label: NSAID #2

Type: Active Comparator

Description: Naproxen and Celecoxib Placebo

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov