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)

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Cerebrovascular Disorders; Arthritis
• Intervention / Treatment: Drug: Celecoxib(drug); Drug: Naproxen(drug)

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.

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Shatin, Hong Kong, China
      • Endoscopy Center, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: NSAID #1; Celecoxib and Naproxen Placebo	Drug: Celecoxib(drug); Celecoxib 100 mg bd; Other Names: Celebrex
ACTIVE_COMPARATOR: NSAID #2; Naproxen and Celecoxib Placebo	Drug: Naproxen(drug); Naproxen 500 mg bd; Other Names: Naprosyn

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrent ulcer bleeding within 18 months according to pre-specified criteria	18 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (ESTIMATE): September 12, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): January 2, 2017
• Last Update Submitted That Met QC Criteria: December 30, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Joint Diseases; Musculoskeletal Diseases; Cardiovascular Diseases; Arthritis; Cerebrovascular Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Gout Suppressants; Celecoxib; Naproxen
• Other Study ID Numbers: 8N Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO