A Comparison of Safety and Treatment in Subjects With Osteoarthritis Taking Low Dose Aspirin

A Randomized, Double-Blind, Phase 3 Study to Compare the Efficacy and Safety of Lansoprazole 30 mg QD and Naproxen 500 mg BID Versus Celecoxib 200 mg QD in Risk Reduction of Non Steroidal Anti-Inflammatory-Associated Ulcers in Osteoarthritis Subjects Taking Low Dose Aspirin

The purpose of this study is to compare the gastroduodenal ulceration rate, gastrointestinal complication rate and non-steroidal anti-inflammatory drug-associated dyspepsia between lansoprazole, naproxen and celecoxib, taken once daily (QD) or twice daily (BID), in participants with osteoarthritis taking low dose aspirin.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis; Peptic Ulcer
• Intervention / Treatment: Drug: Lansoprazole and naproxen and aspirin; Drug: Celecoxib and aspirin

Detailed Description

This study was designed to compare the effectiveness of reducing the incidence of gastroduodenal ulcers between lansoprazole 30mg QD + naproxen 500mg BID vs celecoxib 200mg QD in subjects with osteoarthritis taking low dose aspirin. Approximately 100 sites across the U.S. will enroll subjects with normal endoscopic findings and negative H.pylori. The duration of the study will be a maximum of 14 weeks including a screening period of up to 2 weeks and a 12 week treatment period. Gelusil will be provided for dyspepsia symptom rescue.

• Study Type: Interventional
• Enrollment (Actual): 1045
• Phase: Phase 3

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:

• Must require the chronic use of a non-steroidal anti-inflammatory drug for the treatment of osteoarthritis.
• Must be taking daily aspirin for cardiovascular prophylaxis.
• Clinical Laboratory values within normal limits for this population

Exclusion Criteria:

• History of gastric, duodenal or esophageal surgery except simple oversew of an ulcer.
• Evidence of uncontrolled, clinically significant disease.
• History of cancer within the past 5 years.
• Presence of gastroduodenal ulcers, esophageal ulcer or >= 10 gastroduodenal erosions during the screening endoscopy. Known history of gastroduodenal ulcer or bleeding within the past year. Esophageal stricture requiring dilatation.
• Presence of Barrett's esophagus with dysplastic changes.
• Systemic disease affecting the esophagus or a history of caustic or physiochemical trauma or irradiation to the esophagus.
• Sero-tests positive for H. pylori.
• Evidence of Zollinger-Ellison syndrome, esophageal varices, cholecystitis, or pancreaticobiliary tract disease.
• Requires treatment with an excluded medication such as proton pump inhibitors, histamine H2 receptor antagonists, antacids, corticosteroids, lithium, fluconazole, misoprostol, probenecid, methotrexate, anticoagulants, St. John's wart, dong quai, feverfew, garlic, ginger, horse chestnut, red clover or white willow supplements or bisphosphonates.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lansoprazole 30 mg QD + Naproxen 500 mg BID; (and added aspirin)	Drug: Lansoprazole and naproxen and aspirin; Lansoprazole 30 mg, capsules, orally once daily; Naproxen 500 mg, capsules, orally, twice daily; and aspirin 81 mg or 325 mg, tablets, orally, once daily for up to 12 weeks.
Active Comparator: Celecoxib 200 mg QD; (and added aspirin)	Drug: Celecoxib and aspirin; Celecoxib 200 mg, capsules, orally once daily and aspirin 81 mg or 325 mg, tablets, orally, once daily for up to 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Gastroduodenal ulcers at final visit	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with GI complications (GI bleeding, perforation and gastric outlet obstruction)	Week 12
Severity of each dyspepsia symptom (abdominal pain, nausea, vomiting, heartburn, fullness, and belching) and combined dyspepsia scores.	Weeks 4,8, and 12
Proportion of subjects with dyspepsia at weeks 4, 8, and 12 that did not have dyspepsia at baseline.	Weeks 4,8, and 12
Proportion of subjects without dyspepsia at weeks 4, 8, and 12 who had dyspepsia at baseline.	Weeks 4, 8, and 12
Scores of each SODA scale (pain intensity, non-pain symptoms, and satisfaction) for subjects with dyspepsia.	Weeks 4, 8, and 12
The change from baseline SODA scale for subjects with dyspepsia at baseline.	Weeks 4, 8, and 12

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Goldstein JL, Cryer B, Amer F, Hunt B. Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial. Clin Gastroenterol Hepatol. 2007 Oct;5(10):1167-74. doi: 10.1016/j.cgh.2007.06.009.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): July 1, 2004
• Study Completion (Actual): July 1, 2004

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): July 22, 2010
• Last Update Submitted That Met QC Criteria: July 20, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: NSAIDs; duodenal ulcer; Low dose aspirin; gastric ulcer; Peptic Ulcer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Intestinal Diseases; Duodenal Diseases; Ulcer; Osteoarthritis; Peptic Ulcer; 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; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Gastrointestinal Agents; Cyclooxygenase 2 Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Aspirin; Celecoxib; Dexlansoprazole; Lansoprazole; Naproxen
• Other Study ID Numbers: LAN-0003-0041; U1111-1114-2275 (Registry Identifier: WHO)